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Hippocampal Representational Organization and Spatial Context
Abstract
The hippocampus appears to undergo continual representational reorganization as animals navigate their environments. This reorganization is postulated to be reflected spatially in terms of changes in the ensemble of place cells activated, as well as changes in place field specificity and reliability for cells recorded in both hilar/CA3 and CA1 regions. The specific contribution of the hilar/CA3 region is suggested to be to compare the expected spatial context with that currently being experienced, then relay discrepancies to CA1. The properties of CA1 place fields in part reflect the spatial comparisons made in the hilar/CA3 area. In addition, CA1 organizes the input received from the hilar/CA3 place cells according to different temporal algorithms that are unique to different tasks. In this way, hippocampus helps to distinguish temporally one spatial context from another, thereby contributing to episodic memories.
... The seminal discovery that hippocampal pyramidal neurons exhibit remarkably distinct and reliable firing when rats visit particular regions of the environment led to the highly influential idea that the hippocampus was the neural substrate of the cognitive map (O'Keefe and Nadel, 1978). Over 35 years of study has yielded a vast literature on hippocampal place cells (for reviews, see O'Keefe, 1976;O'Mara, 1995;McNaughton et al., 1996;Muller et al., 1996;Wiener, 1996;Mizumori et al., 1999b). In spite of our remarkably detailed knowledge about factors that influence the response properties of place fields and an extensive literature on the critical role of the hippocampus in certain forms of memory, including apparently nonspatial memory, the fundamental issue of how place fields are related to the broad role of the hippocampus in learning and memory remains unclear. ...
... Hippocampal place cells may represent spatial contexts (Nadel and Wilner, 1980;Nadel and Payne, 2002) such that the extent to which familiar contexts change can be determined, perhaps by performing a match-mismatch comparison (e.g., Vinogradova, 1995;Mizumori et al., 2000bMizumori et al., , 1999bAnderson andjeffery, 2003;Jeffery et al., 2004). Computational models provide suggestions for how such error analyses might be implemented within hippocampal circuitry and modulated by neurotransmitters such as dopamine and acetylcholine (e.g., Lisman, 1999;Hasselmo and McGaughty, 2004;Treves, 2004;Hasselmo, 2005aHasselmo, , 2005b. ...
... There are likely to be multiple stages to the complex process of comparing expected and current contexts (Mizumori et al., 1999b). Initially, relevant stimuli need to be selected for comparison. ...
This chapter focuses on the role of the hippocampus in learning and memory processes. The study was initiated in 1957, after a report showed remarkably severe amnesia in a patient resulting from the surgical removal of the hippocampal formation and a large amount of the adjacent tissue in the medial temporal lobes. This led to the universal consensus that the hippocampus is involved in learning and memory. The unique contribution of hippocampus in learning includes its role in spatial processing, working memory, relational learning, episodic memory, context processing, declarative memory, and the encoding of experiences in general. This chapter evaluates the potential relationship between neural representation by individual hippocampal neurons and learning and memory. The most commonly reported behavioral correlate of hippocampal output neurons (pyramidal cells) is location-selective firing, referred to as place fields. The chapter provides evidence that demonstrates the sensory and movement responsiveness of place fields. It also presents a context discrimination hypothesis to evaluate the role that place fields may play in hippocampal-dependent mnemonic functions.
... The place fields that changed, then, could be thought of as representing current context information. The existence of these two types of place field responses gave rise to the notion that hippocampus compares expected and experienced context features (Mizumori et al., 1999). This idea begs the question, then, why does hippocampus represent both expected (learned) and current context information? ...
... This idea begs the question, then, why does hippocampus represent both expected (learned) and current context information? These hippocampal spatial context representations (O’Keefe and Nadel, 1978; Nadel and Wilner, 1980; Nadel and Payne, 2002) may contribute to a match-mismatch type of analysis that evaluates the present context according to how similar it is to the context that an animal expects to encounter based on past experiences (e.g., Gray, 1982; Vinogradova, 1995; Mizumori et al., 1999, 2000; Gray, 2000; Lisman and Otmakhova, 2001; Hasselmo et al., 2002; Anderson and Jeffery, 2003; Jeffery et al., 2004; Hasselmo, 2005b; Smith and Mizumori, 2006a,b; Manns et al., 2007a; Nadel, 2008). Detected mismatches may be signaled by a change in the pattern of input from hippocampus or possibly by a specific input pattern. ...
... A Context Discrimination Hypothesis (CDH) postulates that single hippocampal neuronal representations of context provide multidimensional data to population-based network computations that ultimately determine whether expected contextual features of a situation have changed (e.g., Mizumori et al., 1999, 2000, 2007a; Smith and Mizumori, 2006a,b; Mizumori, 2008). Initial suggestive evidence of this interpretation of hippocampal network function was the repeated observation that upon less than complete changes in a familiar context, many but not all place fields remap (e.g., Tanila et al., 1997; Mizumori et al., 1999; Brown and Skaggs, 2002; Knierim, 2002; Lee et al., 2004). ...
Events that happen at a particular place and time come to define our episodic memories. Extensive experimental and clinical research illustrate that the hippocampus is central to the processing of episodic memories, and this is in large part due to its analysis of context information according to spatial and temporal references. In this way, hippocampus defines ones expectations for a given context as well as detects errors in predicted contextual features. The detection of context prediction errors is hypothesized to distinguished events into meaningful epochs that come to be recalled as separate episodic memories. The nature of the spatial and temporal context information processed by hippocampus is described, as is a hypothesis that the apparently self-regulatory nature of hippocampal context processing may ultimately be mediated by natural homeostatic operations and plasticity. Context prediction errors by hippocampus are suggested to be valued by the midbrain dopamine system, the output of which is ultimately fed back to hippocampus to update memory-driven context expectations for future events. Thus, multiple network functions (both within and outside hippocampus) combine to result in adaptive episodic memories.
... In these earlier experiments, the term "context" was used to refer to only the external sensory environment. However, more recently, it has become evident that the type of context processing carried out by hippocampus is more complex, and that it includes sensory (external and internal), behavioral, and motivational information that characterizes and defines a specific situation or event (Nadel and Wilner, 1980;Mizumori et al., 1999;Nadel and Payne, 2002;Jeffery et al., 2004;Smith and Mizumori, 2006;Mizumori, 2008a;Penner and Mizumori, 2012a,b). The firing patterns of individual hippocampal neurons change when any aspect of a familiar situation changes, including internal and external sensory information, the behavior and cognitive requirements to achieve a desired goal, one's motivational state, and one's expectations for a particular reward value (e.g., Markus et al 1994;Wood et al., 2000;Jeffery et al., 2004;Yeshenko et al., 2004;Ferbinteneau and Shapiro, 2006;Smith and Mizumori, 2006;Leutgeb et al., 2007). ...
... In freely-navigating animals, hippocampal context information is represented within a spatial framework (Nadel and Wilner, 1980;Mizumori et al., 1999Mizumori et al., , 2000Nadel and Payne, 2002;Mizumori et al., 2007;Mizumori, 2008a,b). A spatial bias to hippocampal neural representations has been described as location-and=or directionally selective firing in mice, rats, bats, birds, and monkeys (O'Keefe, 1976;Rolls et al., 1989;Nakazawa et al., 2002;Hough and Bingman, 2004;Yartsev and Ulanovsky, 2013). ...
... mismatch) conditions (e.g. Mizumori et al., 1999;Kumaran and Maguire, 2007;Mizumori, 2008a,b;Chen et al., 2011;Duncan et al., 2012b;Penner and Mizumori, 2012a). ...
While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The 'multiple memory systems of the brain' have in common output that signals errors in the prediction of events and/or their outcomes, although these signal differ in terms of what the error signal represents (e.g. hippocampus: context prediction errors vs midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. Due to its widespread control and influence, and intrinsic working memory mechanisms, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. Prefrontal cortical regulation of prediction brain areas provides the control needed to continually and automatically produce adaptive responses according to homeostatic regulatory principles: prefrontal cortex serves as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex also restores set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of our model is the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. © 2013 Wiley Periodicals, Inc.
... 4,5). Importantly, because biases in spatial sampling can be correlated with the most recent entryway, we subsampled the data to match the 30 The CA1 rate code represents most recent entryway. If point of entry drives remapping within an environment, then maps of the compartment should be more similar across session halves when the mouse entered from the same entryway as opposed to different entryways. ...
... Consistent with this distinction we observed no coding of future exitway, a component which has been observed in goal-oriented tasks [6][7][8] , suggesting that the DG-CA3-dependent remapping we observed in this paradigm did not reflect planned behavior. We anticipate that a similar experimental approach will help to address several lingering questions, including the relationship between latent, sensory, and goal-oriented rate remapping, the specificity of trisynaptic, lateral entorhinal, and prefrontalthalamic circuit contributions to these forms of rate remapping, and the contribution of the trisynaptic circuit to other forms of hippocampal remapping 5,29,30 . ...
Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Yet, how the hippocampal spatial circuit represents latent information independent of sensory inputs and future goals has not been determined. To address this, we image the activity of large ensembles in subregion CA1 via wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrate that latent information is represented through reliable firing rate changes during unconstrained navigation. We then hypothesize that the representation of latent information in CA1 is mediated by pattern separation/completion processes instantiated upstream within the dentate gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings reveal an analogous code for latent information. Moreover, selective chemogenetic inactivation of DG–CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information. These results reveal a causal and specific role of DG–CA3 circuitry in the maintenance of latent information within the hippocampus. Keinath et al. show that information about the recent past is represented in the hippocampus through changes in firing rates in the absence of task demands. This representation is eliminated when DG–CA3 circuitry is inhibited.
... Importantly, weakened LTP was observed during stimulations at θ-frequency, which is thought to represent a natural pattern of stimulation during spatial exploration in vivo (22,23,26). Increased firing of action potentials by CA3 neurons is thought to induce LTP in CA1 neurons, which contributes to formation and stability of place cells whose firing denotes location during movement (27)(28)(29)(30)(31). Because LTP would contribute to increased excitability of hippocampal place cells during spatial learning (27)(28)(29)(30)(31), these deficits in LTP we have observed would be expected to cause deficits in spatial learning and memory in IM-AA mice. ...
... Increased firing of action potentials by CA3 neurons is thought to induce LTP in CA1 neurons, which contributes to formation and stability of place cells whose firing denotes location during movement (27)(28)(29)(30)(31). Because LTP would contribute to increased excitability of hippocampal place cells during spatial learning (27)(28)(29)(30)(31), these deficits in LTP we have observed would be expected to cause deficits in spatial learning and memory in IM-AA mice. Impaired Spatial Learning and Memory. ...
Significance
Learning and memory are caused by changes in strength of communication between neurons at synapses. Both brief changes (short-term plasticity) and long-lasting changes (long-term plasticity) are important. Synaptic transmission is initiated by calcium channels, which are regulated by calcium-sensor proteins that induce short-term synaptic plasticity. We studied genetically modified mice with a mutation in the binding site for calcium-sensor proteins on calcium channels, which alters short-term synaptic plasticity. Surprisingly, we found that synapses in the hippocampus of these mice also have impaired long-term potentiation. In addition, these mutant mice have impaired spatial learning and memory. Our results show that disruption of calcium-channel regulation by calcium-sensor proteins alters both short-term and long-term plasticity, and these changes impair spatial learning and memory.
... Recent investigation of this question led to the proposal of a Context Discrimination Hypothesis (CDH) that postulates that single hippocampal neurons provide multidimensional (context-defining) data to population-based network computations that ultimately determine whether expected contextual features of a situation have changed (e.g. Mizumori et al., 1999Mizumori et al., , 2000Mizumori et al., , 2007aMizumori et al., , 2008aSmith and Mizumori, 2006a,b). Specifically, hippocampal representations of spatial context information (O'Keefe & Nadel, 1978;Nadel & Payne, 2002;Nadel & Wilner, 1980) may contribute to a match-mismatch analysis that evaluates the present context in terms of how similar it is to the context that an animal expected to encounter based on past experiences (e.g. ...
... Specifically, hippocampal representations of spatial context information (O'Keefe & Nadel, 1978;Nadel & Payne, 2002;Nadel & Wilner, 1980) may contribute to a match-mismatch analysis that evaluates the present context in terms of how similar it is to the context that an animal expected to encounter based on past experiences (e.g. Anderson & Jeffery, 2003;Gray, 1982Gray, , 2000Hasselmo, 2005;Hasselmo et al., 2002;Jeffery et al., 2004, Lisman & Otmakhova, 2001Manns et al., 2007a;Mizumori et al., 1999Mizumori et al., , 2000Smith & Mizumori, 2006a,b;Nadel, 2008;Vinogradova, 1995). Human brain imaging studies provide comparable evidence for a match-mismatch function of hippocampus (Chen et al., 2011;Dickerson et al, 2011;Duncan et al., 2012a,b;Foerde & Shohamy, 2011;Kuhl et al., 2010;Kumaran & Maguire, 2007). ...
A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz, Dayan, & Montague, 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo, Lee, & Mizumori, 2013; Puryear, Kim, & Mizumori, 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton, Jo, Clark, Taylor, & Mizumori, 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg may inform VTA about learned goal-directed movement that reflects the current motivational state, and this in turn may guide VTA determination of expected subjective goal values. When combined it is clear the LDTg and PPTg provide only a portion of the information that dopamine cells need to assess the value of prediction errors, a process that is essential to future adaptive decisions and switches of cognitive (i.e. memorial) strategies and behavioral responses.
... CA3 is theorized to function as an autoassociative network supporting rapid formation of arbitrary associations, and the subsequent retrieval of sequential associations from the presentation of a cue (McNaughton and Morris, 1987;Treves and Rolls, 1992;Hasselmo and Wyble, 1997;Kesner, 2007). Therefore, the combined CA3/DG sub-field is ideally positioned to represent the conjunction of spatial and item information, and replay associated representations when such information is presented as a cue (Mizumori et al., 1999;Carr et al., 2011;Sreenivasan and Fiete, 2011). Consistent with this framework, CA3 neurons in rodents show rapid sequential replay of locations along a route from the current position of the animal (Johnson and Redish, 2007;Davidson et al., 2009). ...
... This finding suggests CA3/DG has a persistent role in processing associations of spatial contextual cues across various stages of experience. Research in rodents has previously implicated CA3/DG circuitry in encoding and processing changes in spatial context (Mizumori et al., 1999;Hasselmo, 2005;Lee et al., 2005). Importantly, the recurrent CA3/DG circuitry is thought to be important for pattern completion from sparse cue information (McNaughton and Morris, 1987;Treves and Rolls, 1992;Hasselmo et al., 1995;Levy, 1996;Hasselmo and Wyble, 1997;Gold and Kesner, 2005;Kesner, 2007;Tamminga et al., 2010;Chen et al., 2011;, providing a mechanism for encoded environment features and navigational sequences to be retrieved from the unique starting location presented in the Cue period of our task. ...
When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high-resolution functional magnetic resonance imaging (hr-fMRI) in humans to test whether the CA3/DG hippocampal subfield and parahippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr-fMRI scanning, participants navigated virtual mazes that were well-learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre-scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non-overlapping Cue periods. Trial-by-trial Cue period responses specifically in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL subfields to processing spatial context and route retrieval, and support a prominent role for CA1 in distinguishing overlapping episodes during navigational “look-ahead” periods. © 2014 Wiley Periodicals, Inc.
... No deficits in locomotion or anxiety were detected in EfnB1 Y/2 mice; however, they exhibited a specific impairment in non-spatial learning and memory tasks. Given that we observed no impairment in spatial learning, which strongly implicates the hippocampus (reviewed in [23,24]) and rather observed learning impairments that are strongly associated with cortical functioning [25,26,27,28], emphasis was placed on analyzing the cortex, specifically the perirhinal cortex, in these mutants. Surprisingly, we established that ephrinB1 does not control learning and memory through modulation of synaptic plasticity in adults, since it is not expressed in the adult brain. ...
... The EfnB1 Y/2 mice displayed no deficit in any of the spatial learning paradigms that are known to strongly involve the hippocampus [23,24]; but rather showed impairment in nonspatial learning tasks that have been shown to be largely independent of hippocampal involvement but involve the cortex [35,36]. To better understand the putative role of ephrinB1 in non-spatial learning and memory, we performed immunohistochemical staining to establish the expression pattern of ephrinB1 in the adult brain. ...
Eph receptors and their ephrin ligands play critical roles in the development of the nervous system, however, less is known about their functions in the adult brain. Here, we investigated the function of ephrinB1, an ephrinB family member that is mutated in CranioFrontoNasal Syndrome. We show that ephrinB1 deficient mice (EfnB1(Y/-) ) demonstrate spared spatial learning and memory but exhibit exclusive impairment in non-spatial learning and memory tasks. We established that ephrinB1 does not control learning and memory through direct modulation of synaptic plasticity in adults, since it is not expressed in the adult brain. Rather we show that the cortex of EfnB1(Y/-) mice displayed supernumerary neurons, with a particular increase in calretinin-positive interneurons. Further, the increased neuron number in EfnB1(Y/-) mutants correlated with shorter dendritic arborization and decreased spine densities of cortical pyramidal neurons. Our findings indicate that ephrinB1 plays an important role in cortical maturation and that its loss has deleterious consequences on selective cognitive functions in the adult.
... Multiple areas in the rodent brain appear to support spatial learning and navigation [1]. The assumption is that these multiple areas function in different but complementary ways. ...
... Despite these apparent simplifications, retrosplenial cortex lesions still markedly impaired acquisition. The finding that the complete retrosplenial lesions did not completely stop learning can be related back to the existence of multiple brain sites supporting spatial learning [1]. ...
The present study examined the consequences of retrosplenial cortex lesions in rats on two novel spatial tasks. In the first experiment, rats discriminated opposing room views from the same general location, along with their opposing directions of travel ('Perspective' task). Rats were trained with food rewards using a go/no-go design. Extensive retrosplenial cortex lesions involving both the granular and dysgranular areas impaired acquisition of this discrimination, which relied on distal visual cues. The same rats were then trained on a non-spatial go/no-go discrimination between different digging media. No lesion effect was apparent. In the final experiment, rats discriminated between two locations within a room ('Location' task) such that direction of travel at each location would be of less help in solving the problem. Both extensive retrosplenial lesions and selective dysgranular retrosplenial lesions impaired this Location task. These results highlight the importance of the retrosplenial cortex (areas 29 and 30), including the dysgranular cortex (area 30), for the effective use of distal visual cues to solve spatial problems. The findings, which help to explain the bias away from visual allocentric solutions that is shown by rats with retrosplenial cortex lesions when performing spatial tasks, also support the notion that the region assists the integration of different categories of visuospatial information.
... This indicates a dissociation between whether a cell fires and where it fires. Place cells are thus responding to a combination of spatial and non-spatial cues, which collectively are often called "spatial context" (Bilkey, 2007;Jeffery et al., 2004;Mizumori et al., 1999;Myers & Gluck, 1994;Oler & Markus, 2000;Russell et al., 2003;Sharp, 1999;Smith & Mizumori, 2006). Spatial context is what drives the map selection process described above. ...
The cognitive map, proposed by Tolman in the 1940s, is a hypothetical internal representation of space constructed by the brain to enable an animal to undertake flexible spatial behaviors such as navigation. The subsequent discovery of place cells in the hippocampus of rats suggested that such a map-like representation does exist, and also provided a tool with which to explore its properties. Single-neuron studies in rodents conducted in small singular spaces have suggested that the map is founded on a metric framework, preserving distances and directions in an abstract representational format. An open question is whether this metric structure pertains over extended, often complexly structured real-world space. The data reviewed here suggest that this is not the case. The emerging picture is that instead of being a single, unified construct, the map is a mosaic of fragments that are heterogeneous, variably metric, multiply scaled, and sometimes laid on top of each other. Important organizing factors within and between fragments include boundaries, context, compass direction, and gravity. The map functions not to provide a comprehensive and precise rendering of the environment but rather to support adaptive behavior, tailored to the species and situation.
... /2023 animal experiences the environment. CA1 is thought to integrate the animal's current experience, represented by inputs from the entorhinal cortex, with representations of past experiences supplied by the direct inputs from CA3 or indirectly from the Dentate Gyrus (DG) (Brun et al., 2002;Grienberger & Magee, 2022;Keinath et al., 2020;Mizumori et al., 1999;Plitt & Giocomo, 2021). It could be that the very first lap is dominated by inputs potentiated by the entorhinal cortex, followed by the CA3 and DG as the animals experience the context and match the current experience with the past. ...
Spatial memory in the hippocampus involves dynamic neural patterns that change over days, termed representational drift. While drift may aid memory updating, excessive drift could impede retrieval. Memory retrieval is influenced by reward expectation during encoding, so we hypothesized that diminished reward expectation would exacerbate representational drift. We found that high reward expectation limited drift, with CA1 representations on one day gradually re-emerging over successive trials the following day. Conversely, the absence of reward expectation resulted in increased drift, as the gradual re-emergence of the previous day's representation did not occur. At the single cell level, lowering reward expectation caused an immediate increase in the proportion of place-fields with low trial-to-trial reliability. These place fields were less likely to be reinstated the following day, underlying increased drift in this condition. In conclusion, heightened reward expectation improves memory encoding and retrieval by maintaining reliable place fields that are gradually reinstated across days, thereby minimizing representational drift.
... In particular, spatial memory is defined as the brain's ability to encode key features of the external environment and to navigate within the boundaries of this mental representation, also known as cognitive map [2,3]. On the physiological level, it manifests as populations of neurons exhibiting activity tuned to specific aspects of the external spatial context, in particular, firing correlated with an animal's presence in a certain, unique location within the environment [4,5]. Such neuron populations, called place cells [6,7], are mainly located in the hippocampus, yet their specificity is influenced by several other groups of spatially tuned neurons, most notably grid cells, border cells and head direction cells [8][9][10][11]. ...
The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in-situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
... Across Alzheimer's disease patient studies and healthy memory studies, the hippocampus has been established to be the single brain region with the most important role (Schwindt and Black, 2009;Kim, 2011). Hippocampal subfield CA1 in particular, appears to be a region that is integral to contextual episodic memory (Mizumori et al., 1999;Leutgeb et al., 2004;Vazdarjanova and Guzowski, 2004;Penner and Mizumori, 2012). CA1 presents atrophy linked to Alzheimer's disease pathology but no volume loss related to normal ageing (Wilson et al., 2004;Frisoni et al., 2008;Yushkevich et al., 2015). ...
Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer's disease. In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel's overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-β42 (<1098) correlated negatively with eigenvector centrality in the anterior cingulate cortex and primary motor cortex; and (iii) abnormal CSF phosphorylated tau levels (>19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies.
... Previous lesion and pharmacological work has suggested that afferents from the hippocampus to the lateral septum are necessary for behavioral responses to context-dependent associations in navigational and conditioning tasks [15][16][17][18][19], and a pathway from the hippocampus to the VTA, through the caudodorsal LS, is essential for linking context and place information with reward [11,20]. Although the hippocampus likely contributes spatial context discrimination [21][22][23][24][25] and spatial coding [26][27][28] to the VTA [29], the role of the LS is less established. It has been hypothesized that the LS may be involved in representing other factors, such as non-spatial context, goals, rewards, or actions [11,20,30]. ...
The lateral septum (LS) has been implicated in anxiety and fear modulation and may regulate interactions between the hippocampus and regions, such as the VTA, that mediate goal-directed behavior. In this study, we simultaneously record from cells in the LS and the hippocampus during navigation and conditioning tasks. In the LS, we identify a speed and acceleration spiking code that does not map to states of anticipation or reward. Additionally, we identify an overlapping population of LS cells that change firing to cue and reward during conditioning. These cells display sharp wave ripple and theta modulation, spatial firing fields, and responses similar to the hippocampus during conditioning. These hippocampus-associated cells are not disproportionately speed or acceleration modulated, suggesting that these movement correlates are not hippocampally derived. Finally, we show that LS theta coordination is selectively enhanced in hippocampus-associated LS cells during navigation behavior that requires working memory. Taken together, these results suggest a role for the LS in transmitting spatial and contextual information, in concert with locomotor information, to downstream areas, such as the VTA, where value weighting may take place.
... Across AD patient studies and healthy memory studies, the single brain region with the most important role has been established to be the hippocampus (Kim 2011;Schwindt and Black, 2009). Hippocampal subfield CA1 in particular, appears to be a region that is integral to contextual episodic memory (Penner and Mizumori, 2012;Mizumori et al., 1999;Leutgeb et al., 2004;Vazdarjanova and Guzowski, 2004). CA1 presents atrophy linked to AD pathology but no volume loss related to normal aging (Frisoni et al., 2008;Wilson et al., 2004;Yushkevich et al., 2015). ...
Hippocampal down-regulation is associated with genetic predisposition to Alzheimer disease (AD), neurodevelopmental processes and disease symptoms. Resting state eigenvector centrality (EC) patterns resemble those of FDG-PET in AD, they can predict self-regulation performance and they are related to functional compensation across the pathophysiological continuum of AD. We acquired cerebrospinal fluid (CSF) biomarkers from a cognitively unimpaired sample at risk for AD (N=48), to investigate the effect of β-amyloid peptide 42 (Aβ42) and phosphorylated tau (p-Tau) levels on EC during the down-regulation of hippocampal subfield cornu ammonis 1, with real-time fMRI closed-loop neurofeedback. Controlling the effects of confounding variables (age, sex, number of APOE ε4 alleles, cognitive reserve, brain reserve and hippocampal down-regulation performance), CSF Aβ42 levels correlated positively with EC in the anterior cingulate cortex (BA24, BA32) and primary motor cortex (BA4). CSF p-Tau levels correlated with EC positively in the ACC (BA32, BA10) ventral striatum (caudate, nucleus accumbens, putamen) and left primary somatosensory cortex (BA2), as well as negatively in the posterior cingulate cortex, precuneus, cuneus and left frontal pole (BA9). Controlling for CSF biomarkers and other prognosis variables, age correlated negatively with EC in the midcingulate cortex, insula, primary somatosensory cortex (BA2) and inferior parietal lobule (BA40), as well as positively with EC in the inferior temporal gyri. Taken together, we identified patterns of functional connectomics in individuals at risk of AD during hippocampal down-regulation, which resemble those found during resting state at advanced AD stages. Moreover, we provide a standard paradigm to replicate and extend this work on a global level. This opens new avenues for further research applications, which quantify and monitor disease progression, by identifying early alterations in the self-regulation of brain function, with potential for non-invasive prognostic screening.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
This article argues that rapid eye movement (REM) dreaming is elaborative encoding for episodic memories. Elaborative encoding in REM can, at least partially, be understood through ancient art of memory (AAOM) principles: visualization, bizarre association, organization, narration, embodiment, and location. These principles render recent memories more distinctive through novel and meaningful association with emotionally salient, remote memories. The AAOM optimizes memory performance, suggesting that its principles may predict aspects of how episodic memory is configured in the brain. Integration and segregation are fundamental organizing principles in the cerebral cortex. Episodic memory networks interconnect profusely within the cortex, creating omnidirectional "landmark" junctions. Memories may be integrated at junctions but segregated along connecting network paths that meet at junctions. Episodic junctions may be instantiated during non-rapid eye movement (NREM) sleep after hippocampal associational function during REM dreams. Hippocampal association involves relating, binding, and integrating episodic memories into a mnemonic compositional whole. This often bizarre, composite image has not been present to the senses; it is not "real" because it hyperassociates several memories. During REM sleep, on the phenomenological level, this composite image is experienced as a dream scene. A dream scene may be instantiated as omnidirectional neocortical junction and retained by the hippocampus as an index. On episodic memory retrieval, an external stimulus (or an internal representation) is matched by the hippocampus against its indices. One or more indices then reference the relevant neocortical junctions from which episodic memories can be retrieved. Episodic junctions reach a processing (rather than conscious) level during normal wake to enable retrieval. If this hypothesis is correct, the stuff of dreams is the stuff of memory.
... Thus, backprojection from CA3 may in uence dentate granule cells (Scharfman, 2007) and the strength of synaptic connections in the di erent pathways of CA3 can then be altered (Marr, 1971;Treves & Rolls, 1994). Several theoretical models are based on these anatomical and physiological characteristics to attribute speci c cognitive processes to CA3 (Marr, 1971;O'Reilly & McClelland, 1994;Treves & Rolls 1994;Hasselmo et al., 1995;Rolls, 1996;Hasselmo & Wyble 1997;Samsonovich & McNaughton 1997;Lisman, 1999;Mizumori et al., 1999;Kesner et al., 2004;. ...
The present thesis work is an attempt to understand the mechanisms of Rxrγ control of memory functions, as well as the potential involvement of dopaminergic signaling in these mecanisms. In this context, I focused my research on hippocampal functions at several distinct levels. The first part of my work (1) aimed at defining the hippocampal cell populations expressing Rxrγ using various histological techniques (immunohistochemistry, in situhybridization) in order to (2) study the electrophysiological functions of these cells using invitro patch-clamp.To identify the role of Rxrγ in the control of cell autonomous functions, as well as the consequences on the surrounding network, I have studied the effects of its loss of function in Rxrγ/mice.As the different subregions of the hippocampus are implicated indistinct aspects of learning and memory, and in particular the dentate gyrus being associated with pattern separation (Leutgeb et al., 2007), I have also tried to dissect the mnemonic processes that rely on Rxrγ activity by performing behavioral analyses of Rxrγ/mice. Considering the transcriptional activities of Rxrγ on Drd2, I have also (4) studied dopaminergic signaling in the hippocampus of wild type and Rxrγ null mutant mice. Finally, to demonstrate the neuroanatomical and homeostatic specificity of Rxrγ control on memory, I performed (5) specific inactivations of Rxrγ in hippocampi of conditional mutant mice that possessed floxed Rxrγ, using AAV vectors expressing recombinase Cre.
... The hippocampal CA1 area is believed to be a critical structure for spatial navigation and memory, as place cells for coding for spatial location as well as the direction and speed of body movement are located in this area [6]. Long-term potentiation (LTP), a long-lasting enhancement of field excitatory postsynaptic potentials (fEPSPs), is easily induced by high-frequency electrical stimulation of Schaffer collaterals/commissural fibers in the CA1 area [7]. ...
Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation.
... Computational (Rolls and Kesner 2006;Hasselmo 2005), lesion Gilbert and Kesner 2003;Hunsaker et al. 2006;Hunsaker et al. 2007), electrophysiological (Brun et al. 2002;Leutgeb et al. 2004;Mizumori et al. 1999), pharmacological (Daumas et al. 2005) and genetic studies (Nakazawa et al. 2002;Nakazawa et al. 2003) indicate that CA3 appears to play an important role in one-trial memory, however almost all of the experiments that have made this conclusion have used tasks involving allocentric space or navigational requirements. Evidence points to CA1 involvement when information must be remembered over a temporal delay (Hunsaker et al. 2006), or consolidated (Daumas et al. 2005). ...
This thesis aims to examine the role of the hippocampus in declarative memory through
the development of animal behavioural models of episodic memory for laboratory rats.
Episodic memory- memory for unique events or episodes- is part of the declarative memory
system thought to be mediated by the medial temporal lobe area of the brain in humans.
One commonly used test of episodic memory in human subjects is paired associate
learning. The first part of this thesis describes the adaptation of this human test for use
with laboratory rats. Using their natural foraging tendency, rats were trained to search
for different flavours of food at different locations within a large enclosure. When cued
with a piece of food of a particular flavour in a separate box, rats learned to return to
the place where that flavour of food had previously been found. This paradigm was
used to investigate the role of the hippocampus in paired-associate learning using temporary
pharmacological inactivation and permanent neurotoxic lesion techniques. The
hippocampus has also been strongly implicated in spatial navigation, learning and memory
in rats and humans. In the experiments described previously, attempts were therefore
made to demonstrate that the results were not confounded by a simple deficit in spatial
navigation.
An alternative approach to studying episodic memory in the laboratory rat is to use
the criteria established by Tulving in 1972 to describe episodic memory. He stated that
episodic memory should encompass the memory for an event and the spatiotemporal
context in which it occurred, i.e. the ”what”, ”where” and ”when” of an event. He later
updated these criteria to include demonstration of autonoetic consciousness- most easily
described as a sense of self awareness. Since this is difficult or impossible to demonstrate
in animals, the term ”episodic-like” memory was coined (Clayton & Dickinson 1998) to
describe the flexible use of information about the spatiotemporal aspects of an event by
non-human species. Since it has been difficult to demonstrate the use of time (when)
in rats (Bird et al; 2003, Babb & Crystal 2006a), Eacott & Norman (2004) suggested that
the ”when” component could be replaced by context; i.e. another element specific to a
particular event that they labelled ”which”. The next part of this thesis describes the use
of the task published by Eacott & Norman to test episodic-like memory in the laboratory
rat. Using the innate spontaneous behaviour of rats to explore novel aspects of their
environment, they were exposed to multiple unique events. These consisted of various
three-dimensional objects being presented in different locations within different contexts.
Their memory for manipulations of the environment was then tested by presenting them
with an event in which one combination of object, location and context was different from
combinations which had previously been encountered. Due to their tendency to explore novel aspects of their environment, normal rats spent the majority of their time exploring
the object that was in a novel location relative to the context in which it was presented.
This successfully demonstrated integrated memory for what, where and which- similar
to that previously defined by Tulving. The rats also showed that they could use this information
flexibly because every trial involved unique combinations of objects, locations
and contexts so there was no inadvertent semantic rule-learning involved. Permanent
neurotoxic lesions of the hippocampus were used to determine the extent to which this
structure is involved in memory for the what, where and which of an event.
The experimental results presented in this thesis demonstrate an indisputable role for
the hippocampus in a variety of tasks designed to parallel episodic memory in humans.
The next steps in this line of research should involve characterisation of the roles of the
various subregions of the hippocampus in episodic-like and paired associate memory.
... In this article, we focus our discussion on the nature of hippocampal context representations and their functional significance for preventing interference. More general discussion of the hippocampal role in contextual memory can be found in several comprehensive reviews (Eichenbaum et al., 2012;Holland and Bouton, 1999;Lee and Lee, 2013;Maren et al., 2013;Mizumori, 2013;Mizumori et al., 1999;Rudy, 2009). Current ideas about the hippocampal role in context coding have come primarily from two parallel streams of research on conditioning and spatial navigation. ...
Context is an essential component of learning and memory processes, and the hippocampus is critical for encoding contextual information. However, connecting hippocampal physiology with its role in context and memory has only recently become possible. It is now clear that contexts are represented by coherent ensembles of hippocampal neurons and new optogenetic stimulation studies indicate that activity in these ensembles can trigger the retrieval of context appropriate memories. We interpret these findings in light of recent evidence that the hippocampus is critically involved in using contextual information to prevent interference, and propose a theoretical framework for understanding contextual influence of memory retrieval. When a new context is encountered, a unique hippocampal ensemble is recruited to represent it. Memories for events that occur in the context become associated with the hippocampal representation. Revisiting the context causes the hippocampal context code to be re-expressed and the relevant memories are primed. As a result, retrieval of appropriate memories is enhanced and interference from memories belonging to other contexts is minimized.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the Quicksand index and corresponding cortical junction can be accessed. ...
I argued that rapid eye movement (REM) dreaming is elaborative emotional encoding for episodic memories, sharing many features with the ancient art of memory (AAOM). In this framework, during non–rapid eye movement (NREM), dream scenes enable junctions between episodic networks in the cortex and are retained by the hippocampus as indices for retrieval. The commentaries, which varied in tone from patent enthusiasm to edgy scepticism, fall into seven natural groups: debate over the contribution of the illustrative dream and disputes over the nature of dreaming (discussed in sect. R1); how the framework extends to creativity, psychopathology, and sleep disturbances (sect. R2); the compatibility of the REM dream encoding function with emotional de-potentiation (sect. R3); scepticism over similarities between REM dreaming and the AAOM (sect. R4); the function of NREM dreams in the sleep cycle (sect. R5); the fit of the junction hypothesis with current knowledge of cortical networks (sect. R6); and whether the hypothesis is falsifiable (including methodological challenges and evidence against the hypothesis) (sect. R7). Although the groups in sections R1–R6 appear quite disparate, I argue they all follow from the associative nature of dreaming.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
Can ancient art of memory (AAOM) principles explain the function of dreaming? The analysis of self-experience in dreams suggests that the answer is no: The phenomenal dream self lacks certain dimensions that are crucial for the efficacy of AAOM in wakefulness. However, the comparison between dreams and AAOM may be fruitful by suggesting new perspectives for the study of lucid dreaming as well an altered perspective on the efficacy of AAOM itself.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
Rapid eye movement (REM) dreaming results in "emotionally intelligent encoding," according to the target article. Building on this, we argue that elaborative encoding alters emotional processing of upcoming events and thereby functions as prospective emotion regulation. After elaborative encoding, future events are appraised differently and result in a redirected emotional response. Disturbed elaborative encoding might be relevant for emotional dysregulation in psychopathology.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
By integrating the classic psychological principles of ancient art of memory (AAOM) with the most recent paradigms in cognitive neuroscience (i.e., the concepts of hodotopic organization and nonlinear dynamics of brain neural networks), Llewellyn provides an up-to-date model of the complex psychological relationships between memory, imagination, and dreams in accordance with current state-of-the-art principles in neuroscience.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
Brain activation patterns and mental, electrophysiological, and neurobiological features of rapid eye movement (REM) sleep suggest more functions than only elaborative encoding. Hence, the periodic occurrence of REM sleep episodes and dreaming may be regarded as a recurrent adaptive interference, which incorporates recent memories into a broader vital context comprising emotions, basic needs and individual genetic traits.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005;Hasselmo et al. 2002;Manns et al. 2007;Mizumori et al. 1999;. For example, if "house on the edge of town" is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the "Quicksand" index and corresponding cortical junction can be accessed. ...
Llewellyn suggests that episodic memories undergo "elaborative encoding" during rapid eye movement (REM) dreams, generating novel associations between recent and remote memories that are then instantiated during non-REM (NREM) sleep. This hypothesis conflicts with our knowledge of the physiology of NREM and then REM sleep stages and their ordered succession. Moreover, associations during sleep might also involve the extraction of hidden patterns rather than de novo associations.
... On the second question, if the hippocampus retains indices, for retrieval to occur, a pattern of incoming external stimuli (or an internal representation/composition) would be matched against these indices. There is considerable evidence that the hippocampus performs a match/mismatch function (Hasselmo 2005; Hasselmo et al. 2002; Manns et al. 2007; Mizumori et al. 1999;. For example, if " house on the edge of town " is the incoming pattern of external stimuli (due to, e.g., a conversation about house purchase), the Quicksand index and corresponding cortical junction can be accessed. ...
This article argues that rapid eye movement (REM) dreaming is elaborative encoding for episodic memories. Elaborative encoding in REM can, at least partially, be understood through ancient art of memory (AAOM) principles: visualization, bizarre association, organization, narration, embodiment, and location. These principles render recent memories more distinctive through novel and meaningful association with emotionally salient, remote memories. The AAOM optimizes memory performance, suggesting that its principles may predict aspects of how episodic memory is configured in the brain. Integration and segregation are fundamental organizing principles in the cerebral cortex. Episodic memory networks interconnect profusely within the cortex, creating omnidirectional "landmark" junctions. Memories may be integrated at junctions but segregated along connecting network paths that meet at junctions. Episodic junctions may be instantiated during non-rapid eye movement (NREM) sleep after hippocampal associational function during REM dreams. Hippocampal association involves relating, binding, and integrating episodic memories into a mnemonic compositional whole. This often bizarre, composite image has not been present to the senses; it is not "real" because it hyperassociates several memories. During REM sleep, on the phenomenological level, this composite image is experienced as a dream scene. A dream scene may be instantiated as omnidirectional neocortical junction and retained by the hippocampus as an index. On episodic memory retrieval, an external stimulus (or an internal representation) is matched by the hippocampus against its indices. One or more indices then reference the relevant neocortical junctions from which episodic memories can be retrieved. Episodic junctions reach a processing (rather than conscious) level during normal wake to enable retrieval. If this hypothesis is correct, the stuff of dreams is the stuff of memory.
... The anatomical and physiological characteristics of the CA3 region -on which converging inputs from a) the entorhinal cortex via the perforant path, b) the dentate gyrus via mossy fibers, and c) its own inputs via the recurrent collaterals -inspired many theoretical models to assign specific cognitive processes to this field. Amongst these, the recurrent collateral circuitry, by which the CA3 pyramidal cells make excitatory synaptic contacts with each other, could serve a critical role in tasks involving rapid contextual representation, novelty detection, and one-trial short-term memory, that all require arbitrary and conjunctive associations [15,16,17,18]. ...
Mutations in the human X-linked doublecortin gene (DCX) cause major neocortical disorganization associated with severe intellectual disability and intractable epilepsy. Although Dcx knockout (KO) mice exhibit normal isocortical development and architecture, they show lamination defects of the hippocampal pyramidal cell layer largely restricted to the CA3 region. Dcx-KO mice also exhibit interneuron abnormalities. As well as the interest of testing their general neurocognitive profile, Dcx-KO mice also provide a relatively unique model to assess the effects of a disorganized CA3 region on learning and memory. Based on its prominent anatomical and physiological features, the CA3 region is believed to contribute to rapid encoding of novel information, formation and storage of arbitrary associations, novelty detection, and short-term memory. We report here that Dcx-KO adult males exhibit remarkably preserved hippocampal- and CA3-dependant cognitive processes using a large battery of classical hippocampus related tests such as the Barnes maze, contextual fear conditioning, paired associate learning and object recognition. In addition, we show that hippocampal adult neurogenesis, in terms of proliferation, survival and differentiation of granule cells, is also remarkably preserved in Dcx-KO mice. In contrast, following social deprivation, Dcx-KO mice exhibit impaired social interaction and reduced aggressive behaviors. In addition, Dcx-KO mice show reduced behavioral lateralization. The Dcx-KO model thus reinforces the association of neuropsychiatric behavioral impairments with mouse models of intellectual disability.
The representation of distinct spaces by hippocampal place cells has been linked to changes in their place fields (the locations in the environment where the place cells discharge strongly), a phenomenon that has been termed 'remapping'. Remapping has been assumed to be accompanied by the reorganization of subsecond cofiring relationships among the place cells, potentially maximizing hippocampal information coding capacity. However, several observations challenge this standard view. For example, place cells exhibit mixed selectivity, encode non-positional variables, can have multiple place fields and exhibit unreliable discharge in fixed environments. Furthermore, recent evidence suggests that, when measured at subsecond timescales, the moment-to-moment cofiring of a pair of cells in one environment is remarkably similar in another environment, despite remapping. Here, I propose that remapping is a misnomer for the changes in place fields across environments and suggest instead that internally organized manifold representations of hippocampal activity are actively registered to different environments to enable navigation, promote memory and organize knowledge.
The ability to make appropriate decisions that result in an optimal outcome is critical for survival. This process involves assessing the environment as well as integrating prior knowledge about the environment with information about one’s current internal state. There are many neural structures that play critical roles in mediating these processes, but it is not yet known how such information coalesces to influence behavioral output. The lateral habenula (LHb) has often been cited as a structure critical for adaptive and flexible responding when environmental contexts and internal state changes. A challenge, however, has been understanding how LHb promotes response flexibility. In this review, we hypothesize that the LHb enables flexible responding following the integration of context memory and internal state information by signaling downstream brainstem structures known to drive hippocampal theta. In this way, animals respond more flexibly in a task situation not because the LHb selects a particular action, but rather because LHb enhances a hippocampal neural state that is often associated with greater attention, arousal, and exploration. In freely navigating animals, these are essential conditions that are needed to discover and implement appropriate alternative choices and behaviors. As a corollary to our hypothesis, we describe short- and intermediate-term functions of the LHb. Finally, we discuss the effects on the behavior of LHb dysfunction in short- and intermediate-timescales, and then suggest that new therapies may act on the LHb to alleviate the behavioral impairments following long-term LHb disruption.
Contextual learning is a critical component of episodic memory and important for living
in any environment. Context can be described as the attributes of a location that
are not the location itself. This includes a variety of non-spatial information that can
be derived from sensory systems (sounds, smells, lighting, etc.) and internal state. In
this review, we first address the behavioral underpinnings of contextual memory and
the development of context memory theory, with a particular focus on the contextual
fear conditioning paradigm as a means of assessing contextual learning and the
underlying processes contributing to it. We then present the various neural centers
that play roles in contextual learning. We continue with a discussion of the current
knowledge of the neural circuitry and physiological processes that underlie contextual
representations in the Entorhinal cortex-Hippocampal (EC-HPC) circuit, as the most well
studied contributor to contextual memory, focusing on the role of ensemble activity as
a representation of context with a description of remapping, and pattern separation
and completion in the processing of contextual information. We then discuss other
critical regions involved in contextual memory formation and retrieval. We finally consider
the engram assembly as an indicator of stored contextual memories and discuss its
potential contribution to contextual memory.
The hippocampus of the mammalian brain supports spatial navigation by building cognitive maps of the environments in which the animal explores. Currently, there is little neurocomputational work investigating the encoding and decoding mechanisms of hippocampal neural representations in large-scale environments. We propose a biologically-inspired hierarchical neural network architecture to learn the transformation of egocentric sensorimotor inputs into allocentric spatial representation for navigation. The hierarchical network is composed of two parallel subnetworks mimicking the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), and one convergent subnetwork mimicking the hippocampus. LEC relays time-related visual information and MEC supplies space-related information in the form of multi-resolution grid codes as resulted from integrating movement information. The convergent subnetwork integrates all information from the parallel subnetworks and predicts the position of the agent in the environment. Synaptic weights of the vision-to-place and grid-to-place connections are learned based on the stochastic gradient descent algorithm. Simulations in a large virtual maze demonstrate that hippocampal place units in the model form multiple and irregularly-spaced place fields, similar to those observed in neurobiological experiments. The model is able to accurately decode the positions of the agent from the learned spatial representations. Moreover, the model is capable of adaptation to degraded visual inputs, and therefore is robust against perturbations. When the motion inputs are deprived, the model meets with localization difficulty, suffering from less accuracy in position predictions.
What has been long absent in understanding the neural circuit that sup- ports spatial processing is a thorough description and rigorous study of the distributed neural networks associated with spatial processing-both in the human as well as in rodents. Most of our understanding regarding the elu- cidation of a spatial neural circuit has been based on rodents and therefore the present manuscript will concentrate on that literature. There is a trend emerging in research to expand beyond the hippocampus for evaluating spa- tial memory, but the thrust of the research still focuses on the role of the hippocampus as essential and other neural substrates as performing sub- servient roles to support hippocampus-dependent spatial processing. This review will describe spatial memory in terms of a system model incorpo- rating partially overlapping and interacting event-based, knowledge-based and rule-based memory systems that are composed of different component processes or attributes associated with spatial processing which are mapped onto the corresponding neural substrates and larger networks. In particular, the interactions among brain systems that process spatial information will be emphasized. We propose that these interactions among brain regions are essential for spatial memory.
The ability to rapidly switch behaviors in dynamic environments is fundamental to survival across species. Recognizing when an ongoing behavioral strategy should be replaced by an alternative one requires the integration of a diverse number of cues both internal and external to the organism including hunger, stress, or the presence of reward predictive cues. Increasingly sophisticated behavioral paradigms coupled with state of the art electrophysiological and pharmacological approaches have delineated a brain circuit involved in behavioral flexibility. However, how diverse contextual cues are integrated to influence strategy selection on a trial by trial basis remains largely unknown. One promising candidate for integration of internal and external cues to determine whether an ongoing behavioral strategy is appropriate is the lateral habenula (LHb). The LHb receives input from many brain areas that signal both internal and external environmental contexts and in turn projects to areas involved in behavioral monitoring and plasticity. This review examines how these connections, combined with recent pharmacological and electrophysiological results reveal a critical role for the LHb in behavioral flexibility in dynamic environments. This proposed role extends the known contributions of the LHb to motivated behaviors and suggests that the fundamental role of the LHb in these behaviors goes beyond signaling rewards and punishments to dopaminergic systems.
Distinguishing spatial contexts is likely essential for the well-known role of the hippocampus in episodic memory. We studied whether types of hippocampal neural organization thought to underlie context discrimination is impacted by learned economic considerations of choice behavior. Hippocampal place cells and theta activity were recorded as rats performed a maze-based probability discounting task that involved choosing between a small certain reward or a large probabilistic reward. Different spatial distributions of place fields were observed in response to changes in probability, the outcome of the rats' choice, and whether or not rats were free to make that choice. The degree to which the reward location was represented by place cells scaled with the expected probability of rewards. Theta power increased around the goal location also in proportion to the expected probability of signaled rewards. Further, theta power dynamically varied as specific econometric information was obtained 'on the fly' during task performance. Such an economic perspective of memory processing by hippocampal place cells expands our view of the nature of context memories retrieved by hippocampus during adaptive navigation. This article is protected by copyright. All rights reserved.
The hippocampus is one of the most researched structures of the brain. Studies of lesions in humans, primates and rodents have suggested to some that the primary role of the hippocampus is to act as a temporary memory buffer which is required for the consolidation of long-term memory. The famous case study of patient H.M., in particular, seemed to suggest that the hippocampus was of crucial importance for memory formation. However, recordings of single neurons in freely moving rodents did not support this notion. In such recordings, neurons were found that were active predominately when the animal passed through a particular area in space. Consequently, these neurons were termed 'place cells' and a theory was developed that suggested that the hippocampus acts as a 'cognitive map' that is required for spatial orientation. It was then found that H.M. had significant damage to his temporal lobes that included the amygdala, rhinal cortices, and other areas. Further case studies and selective hippocampal lesions in primates resulted in much milder amnestic symptoms, and lesions of defined cortical areas in the temporal lobes showed that a number of functions previously attributed to the hippocampus were in fact linked to these areas. Further analysis of neuronal activity in the hippocampus showed that not only is spatial information represented there, but also additional information, such as speed of movement, direction of movement, match or non-match detection, olfactorial identification, and others. In addition, it was found that selective lesions of the hippocampus in rodents impaired spatial navigation and memory formation only mildly. Only simultaneous lesions of several cortical areas in conjunction with the hippocamus could reproduce the impairments and symptoms that were previously thought to be observed after hippocampal lesions alone. In conclusion it is proposed that information processing and memory formation is shared by several brain areas that act as a functional system. This review presents evidence from many different studies that the hippocampus is part of this system and plays a supportive role in associating complex multimodal information and laying down new memory traces. In addition, the concept of allocating specific functions (such as the development of a cognitive map) exclusively to the hippocampus is rejected.
Memory is comprised of many integrated components and functions. Decades ago, Ray Kesner presented an attribute model of memory that provided a functional architecture for memory organization in the brain. Many of the features of the model have been consistently supported by new data, and new discoveries about memory function have often been readily incorporated into the model. Current challenges, then, are to understand what makes each brain area so unique that they mediate different types of memory, and to determine how the different brain areas that process mnemonic information work together in a continuous and seemingly automatic way. The literature shows that the special mnemonic contributions could not be accounted for by unique types of neural representation in different areas of the brain. In fact most memory-related structures show movement-, reward-, and spatial-related neural discharge, although to varying degrees. Also, emerging evidence suggest that the functional consequence of the intrinsic computations of memory structures may be comparable: each may generate a prediction error signal, albeit for different types of information. Task-dependent co-modulation of population efferent codes of distant brain areas (e.g., striatum and hippocampus), however, may importantly determine strategic, memory-driven control over decisions that impact the future selection of responses. The automatic nature of memory-driven strategy switches may depend on a self-regulatory homeostatic system that allows integrative structures like the prefrontal cortex to continuously monitor and control the excitability state of neurons in different memory prediction areas of brain, and in this way enable appropriate control over future decisions.
This chapter presents evidence that (a) the dentate gyrus (DG) has at least three major functions, including conjunctive encoding of multiple sensory inputs, spatial pattern separation, and facilitation of encoding of spatial information; (b) the CA3 has at least three major functions, including short-term memory and rapid encoding, arbitrary associations, and pattern completion; and (c) the CA1 has at least four major functions, including temporal processing of information (temporal order memory), association across time, intermediate memory, and consolidation of new information. It presents additional evidence demonstrating that there are dissociations and associations between the DG and CA3. The dominant view of the relationship between CA3 and CA1 and short-term and intermediate-term memory is that they operate as a feed-forward sequential processing system. The more recent data, however, suggest that, for certain tasks, there are dissociations between short-term and intermediateterm memory and between the involvements of the CA3 and CA1 subregions. Yet, for a different set of tasks, both the CA1 and CA3 interact in processing of short-term and intermediate-term memory.
It is clear from the discussions in previous chapters that the hippocampus contains neural codes that are experience-dependent. Although these codes are typically interpreted in terms of the location of an animal in its environment (i.e. place fields), context-dependent variability (see Chapters 1, 2, and 5) in the firing characteristics of place cells suggests that hippocampal neurons are not representing only absolute sensory space (Nadel et al., 1985). Hippocampus may code information about the spatial context of a situation so that it can identify changes in the significance of environmental cues (Eichenbaum et al., 1999; Mizumori et al., 1999b). Such a function would be particularly useful during new learning.
It has become clear that the hippocampus plays a critical role in the identification of new contexts and for the detection of changes in familiar contexts. The hippocampus accomplishes these goals through a continual process of comparing predicted features of a context or situation to those actually experienced. A mismatch between expected and experienced context expectations is thought to lead to the generation of a context prediction error (Mizumori, 2013) that functionally alerts connected brain areas to alter subsequent decision making and response selection. Little is understood about how hippocampal context analyses impact downstream decision processes. This issue is evaluated here first by comparing the nature of the information represented in hippocampus and decision-related midbrain-striatal structures, while rats perform a hippocampal-dependent spatial memory task in which rewards of different value are found at different locations. In contrast to place-specific and egocentric neural representations, neural representations of goal information are broadly distributed in hippocampal and decision neural circuitry, but they appear in different forms for different brain structures. It is suggested that further researching on how goal information processing occurs in hippocampus and decision neural circuitry may reveal insights into the nature of the interaction between memory and decision systems. The second part of this review describes neural pathways by which hippocampal context information might arrive within the decision circuit. The third section presents a hypothesis that the nature of the interactions between hippocampal and midbrain-striatal circuitry is regulated by the prefrontal cortex.
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A place cell is a neuron that fires whenever the animal traverses a particular location of the environment-the place field of the cell. Place cells are found in two regions of the rodent hippocampus: CA3 and CA1. Motivated by the anatomical connectivity between these two regions and by the evidence for synaptic plasticity at these connections, we study how a place field in CA1 can be inherited from an upstream region such as CA3 through a Hebbian learning rule, in particular, through spike-timing-dependent plasticity (STDP). To this end, we model a population of CA3 place cells projecting to a single CA1 cell, and we assume that the CA1 input synapses are plastic according to STDP. With both numerical and analytical methods, we show that in the case of overlapping CA3 input place fields, the STDP learning rule leads to the formation of a place field in CA1. We then investigate the roles of the hippocampal theta modulation and phase precession on the inheritance process. We find that theta modulation favors the inheritance and leads to faster place field formation whereas phase precession changes the drift of CA1 place fields over time.
This thesis aims to explore the two dominant functional roles of the hippocampal formation, in the
relational encoding of episodic memory and the neural representation of allocentric space, using
a combination of pharmaceutical manipulations and single-unit recording techniques in rodents.
The first part of this thesis focuses on episodic-like memory, defined by the original episodic memory
triad: ‘what-where-when’ (Tulving 1972), which enables the behavioural aspects of episodic
memory to be tested in non-human animals. Permanent neurotoxic lesions of the hippocampus
and it’s subregions were induced to assess their role in a putative episodic-like memory task developed
by Eacott and Norman (2004). In view of the difficulties encountered in successfully
demonstrating the temporal component of episodic-like memory in rats, this task tested integrated
memory for ‘what-where-which’, where the temporal component (when) was replaced with another
event specifier: context (on ‘which’ occasion). Disruption of the hippocampal circuitry led
to a specific impairment in the integration of all three event components, whereas the associative
recognition of any combination of these features in isolation was left intact. These results confirm
the hippocampal dependence of this episodic-like memory task and further reveals the necessity
of both CA3 and CA1, hypothetically due to the underlying autoassociative role of CA3 with CA1
functioning as the vital output pathway for this associated information and/or as a mismatch detector.
There has been much debate over the inclusion of the temporal component and sceptics
may argue that any such interpretations of task-dependence on episodic-like memory processing
are invalid considering the requirement for temporal processing is absent. Due to the proposal that
a temporal framework necessarily provides the foundation on which episodic memories are built,
the second chapter focuses on the development of a suitable protocol in which integrated memory
for the original ‘what-where-when’ episodic memory triad can be reliably tested.
The other main function attributed to the hippocampus was brought to light by the fascinating
revelation that it’s neurons selectively fire in different regions of an environment, termed ‘place
cells’ (O’Keefe and Dostrovsky 1971). From the numerous publications resulting from this discovery
it has emerged that place cells not only respond to the spatial features of the environment
but are also sensitive to a multitude of non-spatial features. These characteristics support the
logical assumption that the primary firing patterns of the hippocampus should underlie it’s main
purported roles, leading to speculations that they reflect episodic memory processes. The second
part of this thesis aims to examine the relationship between hippocampal cells and behaviour by
extending the work of Ainge et al. (2007a), in which a subset of hippocampal place cells were
found to encode both current and intended destination in a double Y-maze ‘win-stay’ task. The
development of these ‘goal-sensitive’ cells were initially investigated during the learning phase of
this task. An exciting pattern of results showed a strong positive correlation between the emergence
of goal-sensitive firing and behavioural performance on the task, tempting speculations that
these firing patterns may underlie spatial learning and future planning, necessary to support performance. To ensure these firing patterns were not a mere reflection of greater experience on the
maze, a second study was conducted in which the task demands changed over set periods of days.
A significant increase in the proportion of cells demonstrating goal-sensitive firing was revealed
when the protocol shifted to incorporate the spatial memory demands of the ‘win-stay’ task, with
all other parameters of the protocol remaining constant. These results support the theory that
goal-sensitive firing patterns are specifically related to the learning and memory demands of the
spatial task, not a result of increased exploration of the maze. The last of this series of studies
assessed hippocampal-dependence of this task and revealed that bilateral hippocampal lesions
induced an impairment in spatial ‘win-stay’ performance. Collectively, these experiments demonstrate
that goal-sensitive firing of hippocampal cells emerge in line with behavioural performance
in a hippocampal-dependent task and the emergence of these firing patterns are specific to the
learning and memory demands of a spatial ‘win-stay’ protocol.
The functional role of the hippocampus in allocentric spatial processing may thus underpin
it’s function in episodic memory and potentially in the imagining and planning of future events,
whereby the hippocampus provides a ‘space’ in which retrieved information can be integrated in
a coherent context to support the fluent and flexible use of information. This hippocampal function
would necessarily require visual information to be accessed, concerning the arrangement of
landmarks and cues within the environment, in association with information regarding internal
orientation and direction and this leads to the question assessed in the final part of this thesis of
where this integration occurs. Based on anatomical evidence and the current literature, the postsubiculum,
an input structure to the hippocampus, emerged as a potential site for the convergence
of sensory cues into the internally generated head direction cell and place cell networks to enable
hippocampal-dependent spatial processing. Thus, the effects of temporary pharmacological
blockade of AMPARs and NMDARs in the postsubiculum were assessed on the encoding of spatial
memory in an object recognition paradigm. The impairment revealed in the ability to recognise
novel object-place configurations demonstrates a key role for NMDAR-dependent plasticity within
the postsubiculum itself in the formation of allocentric spatial memory.
In summary, the experimental results reported in this thesis further elucidate the critical role the
hippocampal formation plays in spatial and episodic memory by combining evidence from cellular
physiology and neuroanatomy to the behaving animal and extends these findings to discuss a more
general role for the hippocampus in imagining both past and future events, in order to successfully
navigate, learn and enable past experience to influence our intended future plans and decisions.
Sleep problems are common in attention-deficit/hyperactivity disorder (ADHD) to the extent that they mimic or exacerbate daytime symptoms expression. In this review, we advocate the need for a better understanding of sleep alterations in youths with ADHD and their impact on neurobehavioral functions including learning, memory and emotional regulation. An in-depth exploration of existing data showed that although extensively studied, the actual nature of sleep problems in ADHD and their effects on daytime behavior are still less well understood. Important issues, among which developmental changes in sleep architecture and role of subtle sleep electroencephalogram signatures, are generally neglected. Future research of sleep effects on behavior in ADHD would benefit from considering developmental aspects and links between brain activation patterns during sleep and wake.
Llewellyn has written a fascinating article about rapid eye movement (REM) dreams and how they promote the elaborative encoding of recent memories. The main message of her article is that hyperassociative and fluid cognitive processes during REM dreaming facilitate consolidation. We consider one potential implication of this analysis: the possibility that excessive or out-of-phase REM sleep fuels dissociative symptomatology. Further research is warranted to explore the psychopathological ramifications of Llewellyn's theory.
Neuroimaging studies show that episodic memory encoding is associated with increased activity in hippocampus and lateral prefrontal cortex; however, the latter structure shows decreased activity in rapid eye movement (REM) sleep. Together with few episodic memory traces in REM sleep, and REM sleep deprivation affecting hippocampus-independent emotional processes, this argues for generic information processing in REM sleep rather than linking episodic memory traces.
It is argued that Llewellyn's hypothesis about the lack of rapid eye movement (REM)-sleep dreaming leading to loss of personal identity and deficits in episodic memory, affectivity, and prospection is insufficiently grounded because it does not integrate data from neurodevelopmental studies and makes reference to an outdated definition of episodic memory.
We propose that rapid eye movement (REM) and slow-wave sleep contribute differently to the formation of episodic memories. REM sleep is important for building up invariant object representations that eventually recur to gamma-band oscillations in the neocortex. In contrast, slow-wave sleep is more directly involved in the consolidation of episodic memories through replay of sequential neural activity in hippocampal place cells.
Llewellyn's claim that rapid eye movement (REM) dream imagery may be related to the processes involved in memory consolidation during sleep is plausible. However, whereas there is voluntary and deliberate intention behind the construction of images in the ancient art of memory (AAOM) method, there is a lack of intentionality in producing dream images. The memory for dreams is also fragile, and dependent on encoding once awake.
A key function of the medial temporal lobe (MTL) is to generate predictions based on prior experience (Bar, 2009). We propose that these MTL-generated predictions guide learning, such that predictions from memory influence memory itself. Considering this proposal within a context-based theory of learning and memory leads to the unique hypothesis that the act of predicting an event from the current context can enhance later memory for that event, even if the event does not actually occur. We tested this hypothesis using a novel paradigm in which the contexts of some stimuli were repeated during an incidental learning task, without the stimuli themselves being repeated. Results from 4 experiments show clear behavioral evidence in support of this hypothesis: Participants were more likely to remember once-presented items if the temporal contexts of those items were later repeated. However, this effect only occurred in learning environments where predictions could be helpful. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
This chapter focuses on the understanding of the structural and process components of memory systems at the psychological and neurobiological levels. Memory is a complex phenomenon, due to a large number of potential interactions that are associated with the organization of memory at the psychological and neural system levels. Most of the neurobiological models of memory postulate an organizational schema involving two or three systems, each supported by different neurobiological substrates and each mediated by different operating characteristics. These systems are labeled event-based, knowledge-based, and rule-based memory, locale versus taxon, working versus reference memory, declarative versus nondeclarative, and declarative versus procedural. However, memory is more complex and involves many neural systems in addition to the hippocampus. Hence, this chapter also discusses Kesner tripartite attribute-based theoretical model of memory to solve this issue. The model is organized into event-based, knowledge-based, and rule-based memory systems; and each system is composed of the same set of multiple attributes or forms of memory characterized by a set of process-oriented operating characteristics; and mapped onto multiple neural regions and interconnected neural circuits.
Three experiments investigated how space is represented in the primate hippocampus by recording the activity of single neurons in the hippocampus of behaving macaque monkeys. In Exp 1, Ss had to remember a stimulus and its position. Neurons that responded differently according to the position on a screen in which the stimulus was shown were analyzed for their spatial fields. In the primate hippocampus many spatial cells (69% of those analyzed) responded in relation to allocentric coordinates. Exp 2 showed that very few hippocampal cells were responsive in a fixation spot stimulus task, and that for the cells that did respond, the encoding was not retinotopic. In Exp 3, it was found that relatively many hippocampal neurons (17%) responded differently according to the spatial position being fixated on the screen. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Cells in both the hippocampus and the subiculum show location related firing patterns, so that the momentary firing rate of a cell is related to the spatial location of a freely moving rat as it navigates in an environment. Since the subiculum receives a strong anatomical projection from the hippocampus, it seems possible that the subicular cell spatial patterns are simply driven by the spatial signals from hippocampal place cells. Data presented here, however, suggest that the two areas code space in fundamentally different ways. Here, spatial firing patterns of individual hippocampal and subicular cells were studied as rats navigated in two different environments. The two chambers were a cylinder and a square, of equal area. For some rats the two chambers were painted to have similar visual stimulus characteristics, while for others, the two were very different. The subicular cells showed very similar firing patterns in the two chambers, regardless of whether they were visually similar or different. In contrast, as predicted based on the findings of earlier studies, hippocampal place cells showed different patterns in the two (again, regardless of their visual similarity). These results suggest that the subicular cells have the ability to transfer a single, abstract spatial representation from one environment to another. This pattern is stretched to fit within the boundaries of the current environment. Thus, the subicular cells seem to provide a generic representation of the geometric relationships between different locations in an environment. It seems possible that this representation may contribute to some navigational abilities exhibited by animals, such as dead reckoning, and novel route generation in unfamiliar environments. In contrast, it appears that hippocampal place cells provide a spatial representation which is unique for each environment and which is strongly influenced by the exact details and overall context of the situation.
The hippocampus has long been thought to be an important cortical region for associative learning and memory. After several decades of experimental and theoretical studies, a picture is emerging slowly of the generic types of learning tasks that this neural structure might be essential for solving. Recently, there have been attempts to unify electrophysiological and behavioral observations from rodents performing spatial learning tasks with data from primates performing various tests of conditional and discrimination learning. Most of these theoretical frameworks have rested primarily on behavioral observations. Complementing these perspectives, we ask the question: given certain physiological constraints at the neuronal and cortical level, what class of learning problems is the hippocampus, in particular, most suited to solve? From a computational point of view, we argue that this structure is involved most critically in learning and memory tasks in which discontiguous items must be associated, in terms of their temporal or spatial positioning, or both.
Medial septal modulation of hippocampal single-unit activity was examined by assessing the behavioral and physiological consequences of reversibly inactivating the medial septum via microinjection of a local anesthetic (tetracaine) in freely behaving rats trained to solve a working memory problem on a radial maze. Reversible septal inactivation resulted in a dramatic, but temporary (15-20 min), impairment in choice accuracy. In addition, movement-induced theta (theta) modulation of the hippocampal EEG was eliminated. Septal injection of tetracaine also produced a significant reduction in location-specific firing by hilar/CA3c complex-spike cells (about 50%), with no significant change in the place-specific firing properties of CA1 complex-spike units. The mean spontaneous rates of stratum granulosum and CA1 theta cells were temporarily reduced by about 50% following septal injection of tetracaine. Although there was a significant reduction in the activities of inhibitory interneurons (theta cells) in CA1, there was no loss of spatial selectivity in the CA1 pyramidal cell discharge patterns. We interpret these results as support for the proposal originally put forth by Marr (1969, 1971) that hippocampal circuits perform pattern completion on fragmentary input information as a result of a normalization operation carried out by inhibitory interneurons. A second major finding in this study was that location specific firing of CA1 cells can be maintained in the virtual absence of the hippocampal theta-rhythm.
The firing rate of hippocampal neurons in rats was related both to spatial location and to multiple behavioral variables as rats performed 2 kinds of tasks that rely on hippocampal function: a spatial navigation task similar in performance demands to the radial-arm maze task and a simultaneous cue odor-discrimination task. In the place task, most cells had distinct single or multiple place fields, that is, neurons increased firing when the rat was in a particular location or locations. However, in most of these cells, firing rate also varied systematically in relation to behavioral variables, including the speed, direction, and turning angle of the rat as it moved through the place field. In addition, the activity of most cells was time-locked to task-relevant approach movements. In the odor task, most cells fired as the rat sampled discriminative cues or when it executed specific, task-relevant approach movements. Some cells fired selectively in relation to which odors were presented, the configuration of odor cues, the locus of the response, or a combination of these variables. Many cells with spatial correlates in the place task also had striking behavioral correlates when rats performed the odor task in the same environment, and the locus of the increased firing associated with behavior in the odor task was not the same as the place field in the place task. Thus, while the complex stimuli that compose spatial cues are reflected in hippocampal neuronal activity, hippocampal processing is not limited to the representation of spatial location. Rather, the domain of hippocampal representation includes both spatial and nonspatial relations among multiple cues and the actions directed in relation to these cues, across cue modalities, and across behavioral paradigms.
Using the techniques set out in the preceding paper (Muller et al., 1987), we investigated the response of place cells to changes in the animal's environment. The standard apparatus used was a cylinder, 76 cm in diameter, with walls 51 cm high. The interior was uniformly gray except for a white cue card that ran the full height of the wall and occupied 100 degrees of arc. The floor of the apparatus presented no obstacles to the animal's motions. Each of these major features of the apparatus was varied while the others were held constant. One set of manipulations involved the cue card. Rotating the cue card produced equal rotations of the firing fields of single cells. Changing the width of the card did not affect the size, shape, or radial position of firing fields, although sometimes the field rotated to a modest extent. Removing the cue card altogether also left the size, shape, and radial positions of firing fields unchanged, but caused fields to rotate to unpredictable angular positions. The second set of manipulations dealt with the size and shape of the apparatus wall. When the standard (small) cylinder was scaled up in diameter and height by a factor of 2, the firing fields of 36% of the cells observed in both cylinders also scaled, in the sense that the field stayed at the same angular position and at the same relative radial position. Of the cells recorded in both cylinders, 52% showed very different firing patterns in one cylinder than in the other. The remaining 12% of the cells were virtually silent in both cylinders. Similar results were obtained when individual cells were recorded in both a small and a large rectangular enclosure. By contrast, when the apparatus floor plan was changed from circular to rectangular, the firing pattern of a cell in an apparatus of one shape could not be predicted from a knowledge of the firing pattern in the other shape. The final manipulations involved placing vertical barriers into the otherwise unobstructed floor of the small cylinder. When an opaque barrier was set up to bisect a previously recorded firing field, in almost all cases the firing field was nearly abolished. This was true even though the barrier occupied only a small fraction of the firing field area. A transparent barrier was effective as the opaque barrier in attenuating firing fields. The lead base used to anchor the vertical barriers did not affect place cell firing.(ABSTRACT TRUNCATED AT 400 WORDS)
Although it has been recognized for some years that each cytoarchitectonic field of Ammon's horn and the subiculum gives rise to a specific pattern of cortical and subcortical projections, it has not been clear whether these various projections arise from different populations of neurons within each field or whether they arise as collaterals from an essentially homogeneous population of cells. We have examined this problem, and the related issue of the origin of the commissural and ipsilateral associational projections of the dentate gyrus, by injecting retrogradely transported fluorescent dyes into two or more of the relevant projection fields in adult rats and subsequently examining the brains for doubly or triply labeled neurons. It is clear from these experiments that at least two of the known efferent projections of field CA1 (to the septum and to the entorhinal cortex) arise from the same pyramidal neurons and also that the commissural, ipsilateral associational, septal, and subicular projections of the other major field of Ammon's horn--field CA3--similarly are due to collaterals. Double-labeling experiments also indicate that at least 80% of the cells in the deep hilar region of the dentate gyrus give rise to both an ipsilateral (associational) and a crossed (or commissural) projection to the dentate granule cells. In contrast, the projection neurons in the dorsal part of the subiculum form a quite heterogeneous population; cells that project to both the septum and the entorhinal area are intermingled with others that project to one or the other area but not to both. The cortical and cortico-subcortical connections of the hippocampal formation thus appear to be quite different from those of the neo-cortex, and the existence of such an extensive system of collateral projections clearly has important consequences for studies of the development of the hippocampus and of its response to selective deafferentation.
When rats forage for randomly dispersed food in a high walled cylinder the firing of their hippocampal "place" cells exhibits little dependence on the direction faced by the rat. On radial arm mazes and similar tasks, place cells are strongly directionally selective within their fields. These tasks differ in several respects, including the visual environment, configuration of the traversable space, motor behavior (e.g., linear and angular velocities), and behavioral context (e.g., presence of specific, consistent goal locations within the environment). The contributions of these factors to spatial and directional tuning of hippocampal neurons was systematically examined in rats performing several tasks in either an enriched or a sparse visual environment, and on different apparati. Place fields were more spatially and directionally selective on a radial maze than on an open, circular platform, regardless of the visual environment. On the platform, fields were more directional when the rat searched for food at fixed locations, in a stereotypic and directed manner, than when the food was scattered randomly. Thus, it seems that place fields are more directional when the animal is planning or following a route between points of special significance. This might be related to the spatial focus of the rat's attention (e.g., a particular reference point). Changing the behavioral task was also accompanied by a change in firing location in about one-third of the cells. Thus, hippocampal neuronal activity appears to encode a complex interaction between locations, their significance and the behaviors the rat is called upon to execute.
Previous studies have identified neurons in the postsubiculum which discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Anatomical studies have shown that the postsubiculum contains reciprocal connections with the anterior thalamic nuclei (ATN). In order to determine how the head direction (HD) cell signal is processed in the brain, single-unit recordings were monitored in the ATN of freely moving rats in order to characterize their behavioral and spatial correlates. Animals were trained to retrieve food pellets thrown randomly into a cylindrical apparatus containing a single orientation cue. Single unit recordings in the ATN showed that approximately 60% of the recorded cells discharged in relation to the animal's head direction in the horizontal plane. Observation of the animal and quantitative analyses showed that HD cell firing was not dependent on the animal's behavior, trunk position, linear speed, angular head velocity, or location in the environment. Most of these cells were localized to the anterior dorsal thalamic nucleus. Each HD cell contained only one head direction at which the cell discharged maximally and the firing rate decreased linearly away from this preferred direction. The preferred firing directions from all cells recorded were distributed over a 360 degrees range. Quantitative analysis showed that these cells contained similar discharge parameters (peak firing rate, directional firing range) to values reported previously for postsubicular HD cells (Taube et al., 1990a). Experiments involving rotation of the orientation cue showed that the preferred firing direction could be controlled by a salient visual cue. In contrast to postsubicular HD cells, passive rotation of a restrained animal showed that most ATN HD cells ceased discharging when the animal's head was oriented in the preferred direction. These findings demonstrate the presence of HD cells in the ATN and indicate the potential importance of this area for spatial navigation. The origin of the head direction signal is discussed and it is concluded that because of the presence of reciprocal connections between the postsubiculum and the ATN, further studies are required in order to determine the direction in which this head-directional information is flowing. Finally, ATN HD cells differ from postsubicular HD cells by appearing to require volitional motoric input.
Previous studies have shown that hippocampal place fields are controlled by the salient sensory cues in the environment, in that rotation of the cues causes an equal rotation of the place fields. We trained rats to forage for food pellets in a gray cylinder with a single salient directional cue, a white card covering 90 degrees of the cylinder wall. Half of the rats were disoriented before being placed in the cylinder, in order to disrupt their internal sense of direction. The other half were not disoriented before being placed in the cylinder; for these rats, there was presumably a consistent relationship between the cue card and their internal direction sense. We subsequently recorded hippocampal place cells and thalamic head direction cells from both groups of rats as they moved in the cylinder; between some sessions the cylinder and cue card were rotated to a new direction. All rats were disoriented before recording. Under these conditions, the cue card had much weaker control over the place fields and head direction cells in the rats that had been disoriented during training than in the rats that had not been disoriented. For the former group, the place fields often rotated relative to the cue card or completely changed their firing properties between sessions. In all recording sessions, the head direction cells and place cells were strongly coupled. It appears that the strength of cue control over place cells and head direction cells depends on the rat's learned perception of the stability of the cues.
We describe here hippocampal cells that respond during whole-body motion when a monkey is moved on a remote-controlled robot-mounted platform in a cue-controlled test chamber (2 x 2 x 2 m). Some of these cells responded to linear motion, and others to axial rotation. Some of these cells responded when the same motion occurred without a view of the visual field. Such cells appeared to be driven by vestibular inputs. Other cells required a view of the visual field for their response, and these cells appeared to be driven by the visual motion relative to the monkey of the test chamber. Further evidence that this was the case was that some of the cells responded to rotation and linear motion of the test chamber while the monkey remained stationary. Other cells responded to combinations of whole-body motion and a view of the environment. These findings show that information about whole-body motion, as well as about where the animal is looking in an environment, is represented in the primate hippocampus. We suggest that this information is important in spatial memory and thus in spatial navigation.
Hippocampal CA1 and CA3 neurons were recorded in rats performing a delayed-match-to-sample (DMTS) task. Complex spike cells showed significant firing peaks following sample and match responses and during delivery of water reward. Individual cells were classified into 4 subtypes according to the presence or absence of firing in each of these 3 phases. There were significant differences in delay interval firing among the 4 subtypes, but firing during the delay did not predict the correct response: 34% of the cells showed a linear change in firing during the delay. Further analyses revealed significant lever position firing biases in approximately 70% of the cells tested irrespective of subtype. The complexity of firing correlates of the neurons recorded in this DMTS task suggests that the hippocampus divides specific aspects of the performance demands of the task across different cell subtypes, which together provide sufficient information to resolve the matching-to-sample problem on any given trial.
The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animal's head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep-layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2-3 min. After this time, the directional preference (but not specificity) appeared to "rotate" systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems.
Hippocampal 'place' cells and the head-direction cells of the dorsal presubiculum and related neocortical and thalamic areas appear to be part of a preconfigured network that generates an abstract internal representation of two-dimensional space whose metric is self-motion. It appears that viewpoint-specific visual information (e.g. landmarks) becomes secondarily bound to this structure by associative learning. These associations between landmarks and the preconfigured path integrator serve to set the origin for path integration and to correct for cumulative error. In the absence of familiar landmarks, or in darkness without a prior spatial reference, the system appears to adopt an initial reference for path integration independently of external cues. A hypothesis of how the path integration system may operate at the neuronal level is proposed.
The human hippocampus has been implicated in memory, in particular episodic or declarative memory. In rats, hippocampal lesions cause selective spatial deficits, and hippocampal complex spike cells (place cells) exhibit spatially localized firing, suggesting a role in spatial memory, although broader functions have also been suggested. Here we report the identification of the environmental features controlling the location and shape of the receptive fields (place fields) of the place cells. This was done by recording from the same cell in four rectangular boxes that differed solely in the length of one or both sides. Most of our results are explained by a model in which the place field is formed by the summation of gaussian tuning curves, each oriented perpendicular to a box wall and peaked at a fixed distance from it.
Young and old rats performed on a maze according to a forced-choice and then a spatial memory procedure either in the same or a different environment. Aged rats were slower to learn the spatial memory task when tested in the same, but not in a different, room. One interpretation of this pattern of results is that although old rats learn new rules as quickly as young rats, they show less flexibility with old rules and familiar spatial information. Impaired choice accuracy during asymptote performance suggests poor processing of trial-unique information by old rats. Spatial correlates of hippocampal CA1 and hilar cells varied with task demand: CA1 cells of aged rats showed more spatially selective place fields, whereas hilar cells showed more diffuse location coding during spatial memory, and not forced-choice, tests. Such representational reorganization may reflect a compensatory response to age-related neurobiological changes in hippocampus.
Populations of hippocampal neurons were recorded simultaneously in rats shuttling on a track between a fixed reward site at one end and a movable reward site, mounted in a sliding box, at the opposite end. While the rat ran toward the fixed site, the box was moved. The rat returned to the box in its new position. On the initial part of all journeys, cells fired at fixed distances from the origin, whereas on the final part, cells fired at fixed distances from the destination. Thus, on outward journeys from the box, with the box behind the rat, the position representation must have been updated by path integration. Farther along the journey, the place field map became aligned on the basis of external stimuli. The spatial representation was quantified in terms of population vectors. During shortened journeys, the vector shifted from an alignment with the origin to an alignment with the destination. The dynamics depended on the degree of mismatch with respect to the full-length journey. For small mismatches, the vector moved smoothly through intervening coordinates until the mismatch was corrected. For large mismatches, it jumped abruptly to the new coordinate. Thus, when mismatches occur, path integration and external cues interact competitively to control place-cell firing.
When the same box was used in a different environment, it controlled the alignment of a different set of place cells. These data suggest that although map alignment can be controlled by landmarks, hippocampal neurons do not explicitly represent objects or events.
Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function.
A minimal synaptic architecture is proposed for how the brain might perform path integration by computing the next internal representation of self-location from the current representation and from the perceived velocity of motion. In the model, a place-cell assembly called a "chart" contains a two-dimensional attractor set called an "attractor map" that can be used to represent coordinates in any arbitrary environment, once associative binding has occurred between chart locations and sensory inputs. In hippocampus, there are different spatial relations among place fields in different environments and behavioral contexts. Thus, the same units may participate in many charts, and it is shown that the number of uncorrelated charts that can be encoded in the same recurrent network is potentially quite large. According to this theory, the firing of a given place cell is primarily a cooperative effect of the activity of its neighbors on the currently active chart. Therefore, it is not particularly useful to think of place cells as encoding any particular external object or event. Because of its recurrent connections, hippocampal field CA3 is proposed as a possible location for this "multichart" architecture; however, other implementations in anatomy would not invalidate the main concepts. The model is implemented numerically both as a network of integrate-and-fire units and as a "macroscopic" (with respect to the space of states) description of the system, based on a continuous approximation defined by a system of stochastic differential equations. It provides an explanation for a number of hitherto perplexing observations on hippocampal place fields, including doubling, vanishing, reshaping in distorted environments, acquiring directionality in a two-goal shuttling task, rapid formation in a novel environment, and slow rotation after disorientation. The model makes several new predictions about the expected properties of hippocampal place cells and other cells of the proposed network.
A detailed biophysical model of hippocampal region CA3 was constructed to study how GABAergic modulation influences place field development and the learning and recall of sequence information. Simulations included 1,000 multicompartmental pyramidal cells, each consisting of seven intrinsic and four synaptic currents, and 200 multicompartmental interneurons, consisting of two intrinsic and four synaptic currents. Excitatory rhythmic septal input to the apical dendrites of pyramidal cells and both excitatory and inhibitory input to interneurons at theta frequencies provided a cellular basis for the development of theta and gamma frequency oscillations in population activity. The fundamental frequency of theta oscillations was dictated by the driving rhythm from the septum. Gamma oscillation frequency, however, was determined by both the decay time of the gamma-aminobutyric acid-A (GABA(A))-receptor-mediated synaptic current and the overall level of excitability in interneurons due to alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and N-methyl-D-aspartate (NMDA)-receptor-gated channel activation. During theta population activity, total GABA(B)-receptor-mediated conductance levels were found to gradually rise and fall in rhythmic fashion with the predominant population frequency (theta rhythm). This resulted in periodic GABA(B)-receptor-mediated suppression of excitatory synaptic transmission at recurrent collaterals (intrinsic fibers) of pyramidal cells and suppression of inhibitory synaptic transmission to both pyramidal cells and interneurons. To test the ability of the model to learn and recall temporal sequence information, a completion task was employed. During learning, the network was presented a sequence of nonorthogonal spatial patterns. Each input pattern represented a spatial "location" of a simulated rat running a specific navigational path. Hebbian-type learning was expressed as an increase in postsynaptic NMDA-receptor-mediated conductances. Because of several factors including the sparse, asymmetric excitatory synaptic connections among pyramidal cells in the model and a sufficient degree of random "background" firing unrelated to the input patterns, repeated simulated runs resulted in the gradual emergence of place fields where a given cell began to respond to a contiguous segment of locations on the path. During recall, the simulated rat was placed at a random location on the previously learned path and tested to see whether the sequence of locations could be completed on the basis of this initial position. Periodic GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic but not afferent fibers resulted in sensory information about location being dominant during early portions of each theta cycle when GABA(B)-receptor-related effects were highest. This suppression declined with levels of GABA(B) receptor activation toward the end of a theta cycle, resulting in an increase in synaptic transmission at intrinsic fibers and the subsequent recall of a segment of the entire location sequence. This scenario typically continued across theta cycles until the full sequence was recalled. When the GABA(B)-receptor-mediated suppression of excitatory and inhibitory transmission at intrinsic fibers was not included in the model, place field development was curtailed and the network consequently exhibited poor learning and recall performance. This was, in part, due to increased competition of information from intrinsic and afferent fibers during early portions of each theta cycle. Because afferent sensory information did not dominate early in each cycle, the current location of the rat was obscured by ongoing activity from intrinsic sources. (ABSTRACT TRUNCATED)
Previous research has shown that spatial, movement, and reward information is integrated within the ventral striatum (VS). The present study examined the possible contribution of the basolateral nuclei of the amygdala (BLA) to this interaction by examining behavioral correlates of BLA neurons while rats performed multiple memory trials on an 8-arm radial maze. Alternate arms consistently held 1 of 2 different amounts of reward. Recorded cells were correlated with motion, auditory input, space, and reward acquisition. Reward-related units were found that anticipated reward encounter, that responded during reward consumption, and that differentiated between high and low reward magnitude. This is consistent with the hypothesis that BLA neurons may provide the VS with reward-related information that could then be integrated with spatial information to ultimately affect goal-directed behavior.
Information theory is used to derive a simple formula for the amount of information conveyed by the firing rate of a neuron about any experimentally measured variable or combination of variables (e.g. running speed, head direction, location of the animal, etc.). The derivation treats the cell as a communication channel whose input is the measured variable and whose output is the cell's spike train. Applying the formula, we find systematic differences in the information content of hippocampal "place cells" in different experimental conditions. 1 INTRODUCTION Almost any neuron will respond to some manipulation or other by changing its firing rate, and this change in firing can convey information to downstream neurons. The aim of this article is to introduce a very simple formula for the average rate at which a cell conveys information in this way, and to show how the formula is helpful in the study of the firing properties of cells in the rat hippocampus. This is by no means the first a...
The hippocampus and related structures are thought to be capable of: 1) representing cortical activity in a way that minimizes overlap of the representations assigned to different cortical patterns (pattern separation); and 2) modifying synaptic connections so that these representations can later be reinstated from partial or noisy versions of the cortical activity pattern that was present at the time of storage (pattern completion). We point out that there is a tradeoff between pattern separation and completion, and propose that the unique anatomical and physiological properties of the hippocampus might serve to minimize this tradeoff. We use analytical methods to determine quantitative estimates of both separation and completion for specified parameterized models of the hippocampus. These estimates are then used to evaluate the role of various properties and of the hippocampus, such as the activity levels seen in different hippocampal regions, synaptic potentiation and depression, th...
The broad diversity of discharge correlates of hippocampal neurones has provoked controversy. For example, purported behavioural correlates could, instead, be location selectivity (of 'place cells') that is secondarily modulated by sensory stimulation or ongoing movements. In rats trained to perform identical behaviours in four corners of a symmetrical arena, we found hippocampal pyramidal cells discharged selectively as the rats performed task-related behaviours regardless of spatial location. Since the ensemble of these hippocampal neurones comprehensively represented all stages of the task, we propose that each cell represents an element of the temporal organization of the animal's behaviour, complementing the place cell representations of elements of the structure of the environment.
(C) Lippincott-Raven Publishers.
Ensemble recordings of 73 to 148 rat hippocampal neurons were used to predict accurately the animals' movement through their environment, which confirms that the hippocampus transmits an ensemble code for location. In a novel space, the ensemble code was initially less robust but improved rapidly with exploration. During this period, the activity of many inhibitory cells was suppressed, which suggests that new spatial information creates conditions in the hippocampal circuitry that are conducive to the synaptic modification presumed to be involved in learning. Development of a new population code for a novel environment did not substantially alter the code for a familiar one, which suggests that the interference between the two spatial representations was very small. The parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events.
This chapter focuses on the understanding of the structural and process components of memory systems at the psychological and neurobiological levels. Memory is a complex phenomenon, due to a large number of potential interactions that are associated with the organization of memory at the psychological and neural system levels. Most of the neurobiological models of memory postulate an organizational schema involving two or three systems, each supported by different neurobiological substrates and each mediated by different operating characteristics. These systems are labeled event-based, knowledge-based, and rule-based memory, locale versus taxon, working versus reference memory, declarative versus nondeclarative, and declarative versus procedural. However, memory is more complex and involves many neural systems in addition to the hippocampus. Hence, this chapter also discusses Kesner tripartite attribute-based theoretical model of memory to solve this issue. The model is organized into event-based, knowledge-based, and rule-based memory systems; and each system is composed of the same set of multiple attributes or forms of memory characterized by a set of process-oriented operating characteristics; and mapped onto multiple neural regions and interconnected neural circuits. .
discuss several aspects of brain activity processes that have been insufficiently studied, and that are crucial to explore to relate brain mechanisms to cognitive functions and behaviors / briefly summarize the principles of cortical representational plasticity as they are understood at the present time / consider some aspects of what these principles mean for our limited understanding of the functioning of the mind in terms of the brain
perspectives for exploring neural representation [cortical representations are constantly changing, the cortex is a dynamic system in which all representations occur against a backdrop of a continuing, internally generated content, the nervous system functions over time, stimulus representation is by neuronal ensembles, representations are in part relational] / some neurological principles of learning and cortical plasticity [some basic features of cortical representational plasticity, modulatory control of cortical plasticity, representational changes with overlearning, plastic changes underlying the representations of temporal features of stimuli, enduring brain representations of learned behaviors and memories, some implications for system organization and coordination] (PsycINFO Database Record (c) 2012 APA, all rights reserved)
In a series of radial-arm maze experiments to investigate the behavioral functions of the hippocampal system in rats, both the type of stimulus to be remembered (extramaze stimuli with a constant topological relationship or intramaze stimuli with a changing topological relationship) and the type of memory procedure (working memory procedure or reference memory procedure) were manipulated independently. Results provide no support for spatial or cognitive mapping ideas of hippocampal function; a deficit was found in nonspatial versions of the maze, and a dissociation of performance was found in a spatial version. Thus, the important dimension for predicting the effects of hippocampal damage was the type of memory required and not the type of stimulus to be remembered. Peer commentary by 38 researchers and the author's reply are appended. (7 p ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
All recent memory theories of hippocampal function have incorporated the idea that the hippocampus is required to process items only of some qualitatively specifiahle kind, and is not required to process items of some complementary set. In contrast, it is now proposed that the hippocampus is needed to process stimuli of all kinds, but only when there is a need to associate those stimuli with other events that are temporally discontiguous. In order to form or use temporally discontiguous associations, it is essential to maintain some memory of the first component until the second component has occurred. When the temporal gap to he spanned is small, and the number of items to be temporarily retained is low, a limited-capacity, short-term store is sufficient to allow associations to be formed. Such a store is presumed to operate in parallel with the hippocampus in normal animals. Hippocampal damage disrupts a much higher-capacity store that has a slower decay rate, and so leaves animals with only a very limited ability to form temporally discontiguous associations. Hippocampal damage, however, is not held to affect the long-term storage of associations of any kind, if they can be formed. Analyses of both new and existing data are presented to show that by classifying tasks in terms of the need to use a temporary memory store to retain temporally discontiguous information one can cut right across existing classifications as well as achieve a better fit to the data. The hippocampus thus seems best described as a high-capacity, intermediate-term memory store.
We examined the behavioral modulation of head-directional information processing in neurons of the rat posterior cortices, including the medial prestriate (area Oc2M) and retrosplenial cortex (areas RSA and RSG). Single neurons were recorded in freely moving rats which were trained to perform a spatial working memory task on a radial-arm maze in a cue-controlled room. A dual-light-emitting diode (dual-LED) recording headstage, mounted on the animals' heads, was used to track head position and orientation. Planar modes of motion, such as turns, straight motion, and nonlocomotive states, were categorized using an objective scheme based upon the differential contributions of movement parameters, including linear and angular velocity of the head. Of 662 neurons recorded from the posterior cortices, 41 head-direction (HD) cells were identified based on the criterion of maintained directional bias in the absence of visual cues or in the dark. HD cells constituted 7 of 257 (2.7%) cells recorded in Oc2M, 26 of 311 (8.4%) cells in RSA, and 8 of 94 (8.5%) cells in RSG. Spatial tuning of HD cell firing was modulated by the animal's behaviors in some neurons. The behavioral modulation occurred either at the preferred direction or at all directions. Moreover, the behavioral selectivity was more robust for turns than straight motions, suggesting that the angular movements may significantly contribute to the head-directional processing. These behaviorally selective HD cells were observed most frequently in Oc2M (4/7, 57%), as only 5 of 26 (19%) of RSA cells and none of the RSG cells showed behavioral modulation. These data, taken together with the anatomical evidence for a cascade of projections from Oc2M to RSA and thence to RSG, suggest that there may be a simple association between movement and head-directionality that serves to transform the egocentric movement representation in the neocortex into an allocentric directional representation in the periallocortex.
The current view of the role of GABAergic interneurones in cortical-network function has shifted from one of merely dampening neuronal activity to that of an active role in information processing. In this review, we explore a potential role of hippocampal GABAergic interneurones in providing spatial and temporal conditions for modifications of synaptic weights during hippocampus-dependent memory processes. We argue that knowledge of spatiotemporal activity patterns in distinct classes of interneurone is essential to understanding the cellular mechanisms underlying learning and memory.
Single units were recorded from the CA1 field of the hippocampus in the freely-moving rat. They were classified as place units, displace units or others. Place units were defined as those for which the rat's position on the maze was a necessary condition for maximal unit firing. Some of these place units (misplace units) fired maximally when the animal sniffed in a place, either because it found something new there or failed to find something which was usually there. Displace units increased their rates during behaviors associated with theta activity in the hippocampal slow waves. In general these were behaviors which changed the rat's position relative to the environment. The influence of various environmental manipulations (e.g., turning off the room lights) on the firing pattern of the place units was tested and the results suggest that they were not responding to a simple sensory stimulus nor to a specific motor behavior. Nor could the unit firing be due purely to motivational or incentive factors. The results are interpreted as strong support for the cognitive map theory of hippocampal function.
The projections of the supramammillary nucleus (SUM) were examined in the rat by the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from SUM ascended through the forebrain within the medial forebrain bundle. SUM fibers were found to terminate heavily in the hippocampal formation, specifically within the granule cell layer and immediately adjoining molecular layer of the dentate gyrus. In addition, SUM fibers were shown to distribute densely to several structures with strong connections with the hippocampus, namely, the nucleus reuniens of the thalamus, the medial and lateral septum, the entorhinal cortex, and the endopiriform nucleus.
SUM fibers were also shown to project significantly to several additional subcortical and cortical sites. The subcortical sites were the dorsal raphe nucleus, the midbrain central gray, the fields of Forel/zona incerta, the dorsomedial hypothalamic area, midline/intralaminar nuclei of the thalamus (posterior paraventricular, rhomboid, central medial, intermediodorsal, and mediodorsal), the medial and lateral preoptic areas, the bed nucleus of the stria terminalis, the substantia innominata, the vertical limb of the diagonal band nucleus, and the claustrum. The cortical sites were the occipital, temporal, parietal, and frontal cortices.
Some notable differences were observed in projections from the lateral as compared to the medial SUM. For example, fibers originating from the lateral SUM distributed heavily to the hippocampal formation and parts of the cortex, whereas those from the medial SUM projected sparsely to these two regions.
The SUM projections to the hippocampal formation and associated structures may serve as the substrate for a SUM involvement in the generation of the theta rhythm of the hippocampus and the gating of information flow through the hippocampal formation.
The activity of individual pyramidal cells in the CA1 and CA3 subfields of the rodent hippocampus exhibits a remarkable selectivity for specific locations and orientations of the rat within spatially-extended environments. These cells exhibit high rates of activity when the animal is present within restricted regions of space, referred to as place fields, and are extremely quiet when it is elsewhere. Although this phenomenon has been well studied in the CA fields of the hippocampus, relatively little is known about the spatial and temporal firing characteristics either of the entorhinal cortical inputs to the hippocampus, or of the subicular recipients of the output of hippocampal place cells. We report here on a comparison of spatial and temporal discharge characteristics among entorhinal cortex, CA3 and CA1, and the subiculum. CA3 complex spike cells were significantly more spatially specific than their CA1 counterparts. Neither entorhinal cortex nor subiculum exhibited the highly localized patterns of spatial firing observed in the CA fields. In addition, average discharge rates in these areas were substantially higher. However, particularly in subiculum, there was evidence for spatially consistent, but dispersed, firing in some cells, suggestive of the convergence of a number of CA1 place cells. The patterns observed are not consistent with the hypothesis that spatial selectivity is progressively refined at the various levels of hippocampal processing. Rather, hippocampal output appears to be expressed as a much more highly distributed spatial code than activity within the hippocampus proper. We suggest that the sparse coding used within the hippocampus itself represents a mechanism for increasing the storage capacity of a network whose function is to form associations rapidly.
Isolated single units in rat dorsal hippocampus and fascia dentata were classified as 'Theta' or 'Complex-Spike' cells, and their firing characteristics were examined with respect to position, direction and velocity of movement during forced choice, food rewarded search behavior on a radial eight arm maze. Most spikes from CS cells occurred when the animal was located within a particular place on the maze and moving in a particular direction. Theta cells had very low spatial selectivity. Both cell categories had discharge probabilities which increased somewhat as a function of running velocity but tended to asymptote well before half-maximal velocity. The place/direction specificity of CS cells was significantly higher in CA1 than in CA3 and CA3 CS cells exhibited a striking preference for the inward radial direction. The pronounced directional selectivity of CS cells, at least in the present environment, suggests that they fire in response to complex, but specific, stimulus features in the extramaze world rather than to absolute place in a non-egocentric space. An alternative possibility is that the geometrical constraints of the maze surface have a profound influence on the shapes of the response fields of CS cells.
The hippocampus and related structures are thought to be capable of 1) representing cortical activity in a way that minimizes overlap of the representations assigned to different cortical patterns (pattern separation); and 2) modifying synaptic connections so that these representations can later be reinstated from partial or noisy versions of the cortical activity pattern that was present at the time of storage (pattern completion). We point out that there is a trade-off between pattern separation and completion and propose that the unique anatomical and physiological properties of the hippocampus might serve to minimize this trade-off. We use analytical methods to determine quantitative estimates of both separation and completion for specified parameterized models of the hippocampus. These estimates are then used to evaluate the role of various properties and of the hippocampus, such as the activity levels seen in different hippocampal regions, synaptic potentiation and depression, the multi-layer connectivity of the system, and the relatively focused and strong mossy fiber projections. This analysis is focused on the feedforward pathways from the entorhinal cortex (EC) to the dentate gyrus (DG) and region CA3. Among our results are the following: 1) Hebbian synaptic modification (LTP) facilitates completion but reduces separation, unless the strengths of synapses from inactive presynaptic units to active postsynaptic units are reduced (LTD). 2) Multiple layers, as in EC to DG to CA3, allow the compounding of pattern separation, but not pattern completion. 3) The variance of the input signal carried by the mossy fibers is important for separation, not the raw strength, which may explain why the mossy fiber inputs are few and relatively strong, rather than many and relatively weak like the other hippocampal pathways. 4) The EC projects to CA3 both directly and indirectly via the DG, which suggests that the two-stage pathway may dominate during pattern separation and the one-stage pathway may dominate during completion; methods the hippocampus may use to enhance this effect are discussed.
We examined the behavioral modulation of head-directional information processing in neurons of the rat posterior cortices, including the medial prestriate (area Oc2M) and retrosplenial cortex (areas RSA and RSG). Single neurons were recorded in freely moving rats which were trained to perform a spatial working memory task on a radial-arm maze in a cue-controlled room. A dual-light-emitting diode (dual-LED) recording headstage, mounted on the animals' heads, was used to track head position and orientation. Planar modes of motion, such as turns, straight motion, and nonlocomotive states, were categorized using an objective scheme based upon the differential contributions of movement parameters, including linear and angular velocity of the head. Of 662 neurons recorded from the posterior cortices, 41 head-direction (HD) cells were identified based on the criterion of maintained directional bias in the absence of visual cues or in the dark. HD cells constituted 7 of 257 (2.7%) cells recorded in Oc2M, 26 of 311 (8.4%) cells in RSA, and 8 of 94 (8.5%) cells in RSG. Spatial tuning of HD cell firing was modulated by the animal's behaviors in some neurons. The behavioral modulation occurred either at the preferred direction or at all directions. Moreover, the behavioral selectivity was more robust for turns than straight motions, suggesting that the angular movements may significantly contribute to the head-directional processing. These behaviorally selective HD cells were observed most frequently in Oc2M (4/7, 57%), as only 5 of 26 (19%) of RSA cells and none of the RSG cells showed behavioral modulation. These data, taken together with the anatomical evidence for a cascade of projections from Oc2M to RSA and thence to RSG, suggest that there may be a simple association between movement and head-directionality that serves to transform the egocentric movement representation in the neocortex into an allocentric directional representation in the periallocortex.
Previous behavioral and acute electrophysiological data have lead researchers to speculate that the nucleus accumbens integrates limbic, reward and motor information. The present study examined the behavioral correlates to single unit activity of the nucleus accumbens and surrounding ventral striatum as a means of evaluating the integrative functioning of this region in an awake animal. Medial ventral striatum (mVS) activity was recorded as rats completed multiple trials on an eight arm radial maze. Neuronal activity was found to correlate with spatial, reward- and movement-related behavioral conditions. While the majority of cells demonstrated correlates of a single type (i.e. either spatial or reward correlates), 6 cells encoded multiple correlates of different types (i.e. spatial and reward correlates). The data suggests that this integrative process can be active both at the level of the individual neuron, and at the structural level. These results are consistent with the hypothesis that the mVS integrates spatial and reward-related information, which in turn influences voluntary motor output structures in order to achieve accurate navigational behavior.
Ensemble recordings of 73 to 148 rat hippocampal neurons were used to predict accurately the animals' movement through their environment, which confirms that the hippocampus transmits an ensemble code for location. In a novel space, the ensemble code was initially less robust but improved rapidly with exploration. During this period, the activity of many inhibitory cells was suppressed, which suggests that new spatial information creates conditions in the hippocampal circuitry that are conducive to the synaptic modification presumed to be involved in learning. Development of a new population code for a novel environment did not substantially alter the code for a familiar one, which suggests that the interference between the two spatial representations was very small. The parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events.
With the exception of a report by R. B. Veazey, D. G. Amaral, and W. M. Cowan (1982, J. Comp. Neurol. 207:135–156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris -leucoagglutinin (PHA-L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of atria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices.
The diversity of PH projections to subcortical and cortical “limbic-related” sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events.
Hippocampal 'place cells' discharge when a rat occupies a location that is fixed in relation to environmental landmarks. A principal goal of this study was to determine whether hippocampal place cell activity could be influenced by inertial cues. Water-deprived rats were trained in a square-walled open field in a dark room. The behavioral task required alternating visits to water reservoirs in the centre and in the four corners of the arena. The rat and arena were rotated in total darkness through +/-90, 180 or 270 degrees C. The next water reward was then presented in the corner at the same position relative to the outside room as before the rotation. A cue card was later illuminated in this corner as a visual cue for the extra-arena (room) reference frame. Fifteen out of 97 recorded hippocampal CA1 complex spike cells had spatially selective discharges in non-central parts of the arena. After arena rotations, the firing fields of three units shifted between corners of the arena to maintain a fixed orientation relative to the room. This indicates that the hippocampus updated its representation of the position and heading direction of the rat using vestibular-derived inputs concerning rotation angle. Other spatially selective discharges were guided to landmark cues (cue card or position of the reward: two units) or arena-locked 'substratal' cues (eight units). In six cells, place cell activity suddenly ceased or appeared following rotations. These results provide evidence for contributions of inertial as well as substratal and landmark information to hippocampal spatial representations.
The broad diversity of discharge correlates of hippocampal neurones has provoked controversy. For example, purported behavioural correlates could, instead, be location selectivity (of 'place cells') that is secondarily modulated by sensory stimulation or ongoing movements. In rats trained to perform identical behaviours in four corners of a symmetrical arena, we found hippocampal pyramidal cells discharged selectively as the rats performed task-related behaviours regardless of spatial location. Since the ensemble of these hippocampal neurones comprehensively represented all stages of the task, we propose that each cell represents an element of the temporal organization of the animal's behaviour, complementing the place cell representations of elements of the structure of the environment.
First, what is computed by the hippocampus is considered. Based on the effects of damage to the hippocampus and neuronal activity recorded in the primate hippocampus, it is suggested that it is involved in associating together information usually originating from different cortical regions, for example, about objects and their place in a spatial environment. The rapid formation of such context-dependent memories is prototypical of memories of particular events or episodes. Second, a computational theory of how it performs this function, based on neuroanatomical and neurophysiological information about the different neuronal systems contained within the hippocampus, is described. Key hypotheses are that the CA3 pyramidal cells operate as a single autoassociation network to store new episodic information as it arrives via a number of specialized preprocessing stages from many different association areas of the cerebral cortex, and that the dentate granule cell/mossy fiber system is important particularly during learning to help to produce a new pattern of firing in the CA3 cells for each episode. The computational analysis shows how many memories could be stored in the hippocampus, and how quickly the CA3 autoassociation system would operate during recall. The analysis is then extended to show how the CA3 system could be used to recall the whole of an episodic memory when only a fragment of it is presented. It is shown how this retrieval within the hippocampus could lead to recall of neuronal activity in association areas of the cerebral neocortex similar to that present during the original episode, via modified synapses in backprojection pathways from the hippocampus to the cerebral neocortex. The recalled information in the cerebral neocortex could then by used by the neocortex in the formation of long-term memories and/or in the selection of appropriate actions.
The use of genetically engineered mice has been a major development in neuroscience research. Genetic engineering is an undoubtedly powerful technique; however, the value of this approach has been debated, particularly in relation to its use to probe the underlying bases of complex behaviors, such as memory. A recent new development of the technique is the ability to target a specific gene knockout to a particular subregion or even to specific and limited cell types of the mouse brain. An example of this approach is the knockout of the NMDARI gene in only CAI-pyramidal cells of the hippocampus. The resulting animals can be tested by several methods, including in vivo multielectrode recording during behavioral tasks. The data provide strong evidence in favor of the notion that NMDA receptor-dependent synaptic plasticity at CAI synapses is required for both the acquisition of spatial memory and the formation of normal CAI place fields. This relationship suggests that robust place fields may be essential for spatial memory.
Previously, we found that aged rats showed a significant enhancement of hippocampal CA1 place cell spatial specificity, as well as a reduction of hilar place cell spatial specificity, during asymptote performance of a spatial memory task. Because such an age effect was not observed when animals performed a nonspatial task, the present study tested the hypothesis that the different patterns of spatial selectivity observed in memory and nonmemory tests reflected a redistribution of spatial representations that occurred in response to changing task demands. In the present experiment, after animals became familiar with the test environment and motor demands of performance on a radial maze, CA1 and hilar place cells were recorded as they learned a spatial memory task. CA1 place cells recorded from unimpaired old, but not impaired old or young, animals became more spatially selective as animals learned the task. Hilar spatial selectivity for both age groups was not significantly related to choice accuracy. These data support the hypothesis that at least a subpopulation of aged rats may benefit from reorganization of spatial representations in such a way that the normal age-related spatial learning deficit is attenuated.
To begin investigation of the contribution of the superior colliculus to unrestrained navigation, the nature of behavioral representation by individual neurons was identified as rats performed a spatial memory task. Similar to what has been observed for hippocampus, many superior collicular cells showed elevated firing as animals traversed particular locations on the maze, and also during directional movement. However, when compared to hippocampal place fields, superior collicular location fields were found to be more broad and did not exhibit mnemonic properties. Organism-centered spatial coding was illustrated by other neurons that discharged preferentially during right or left turns made by the animal on the maze, or after lateralized sensory presentation of somatosensory, visual, or auditory stimuli. Nonspatial movement-related neurons increased or decreased firing when animals engaged in specific behaviors on the maze regardless of location or direction of movement. Manipulations of the visual environment showed that many, but not all, spatial cells were dependent on visual information. The majority of movement-related cells, however, did not require visual information to establish or maintain the correlates. Several superior collicular cells fired in response to multiple maze behaviors; in some of these cases a dissociation of visual sensitivity to one component of the behavioral correlate, but not the other, could be achieved for a single cell. This suggests that multiple modalities influence the activity of single neurons in superior colliculus of behaving rats. Similarly, several sensory-related cells showed dramatic increases in firing rate during the presentation of multisensory stimuli compared to the unimodal stimuli. These data reveal for the first time how previous findings of sensory/motor representation by the superior colliculus of restrained/anesthetized animals might be manifested in freely behaving rats performing a navigational task. Furthermore, the findings of both visually dependent and visually independent spatial coding suggest that superior colliculus may be involved in sending visual information for establishing spatial representations in efferent structures and for directing spatially-guided movements.
competition between afferent and intrinsic sources resulted in a dal cells and both excitatory and inhibitory input to interneurons tendency for rapid recall of several locations at once, which often at theta frequencies provided a cellular basis for the development lead to inaccuracies in the sequence. Thus the rat often recalled a of theta and gamma frequency oscillations in population activity. path different from the particular one that was learned. GABA B - The fundamental frequency of theta oscillations was dictated by receptor-mediated modulation of excitatory synaptic transmission the driving rhythm from the septum. Gamma oscillation frequency, within a theta cycle resulted in a systematic relationship between however, was determined by both the decay time of the g-aminobu- single-unit activity and peaks in pyramidal cell population behavior tyric acid-A (GABA A )-receptor-mediated synaptic current and the (theta rhythm) . Because