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Hippocampal lesions and path integration
Abstract
Research on spatial problem-solving over the past two years has linked the hippocampus to path integration, that is, the use of movement-related cues to guide spatial behavior. Path integration may underlie the forms of place learning that are impaired by hippocampal damage. It remains a challenge to determine whether path integration is the central function of the hippocampus or but one of many.
... Behavioral neuroscience studies on the foraging behavior of rats have generally linked the hippocampus to path integration (see, e.g., McNaughton et al., 1996;Whishaw et al., 1997;Wiener et al., 1995). Notably, Whishaw et al. (1997) argued that one of the specialized functions of the hippocampus pertains to coding for idiothetic information (e.g., efferent signals to the musculature, afferent proprioception from the muscles and joints) and channeling such information toward the optimal processing of allothetic information (e.g., visual, auditory, olfactory cues; see also Whishaw & Tomie, 1996) Specifically, the relevance of the hippocampus for path integration was demonstrated by random and inaccurate homing responses of rats with lesions to the hippocampus (involving complete lesioning of the dorsal hippocampus, see Maaswinkel et al., 1999;Save et al., 2001) and fimbria-fornix (Whishaw & Gorny, 1999;Whishaw et al., 2001;Whishaw & Maaswinkel, 1998;Whishaw & Tomie, 1996). ...
... Behavioral neuroscience studies on the foraging behavior of rats have generally linked the hippocampus to path integration (see, e.g., McNaughton et al., 1996;Whishaw et al., 1997;Wiener et al., 1995). Notably, Whishaw et al. (1997) argued that one of the specialized functions of the hippocampus pertains to coding for idiothetic information (e.g., efferent signals to the musculature, afferent proprioception from the muscles and joints) and channeling such information toward the optimal processing of allothetic information (e.g., visual, auditory, olfactory cues; see also Whishaw & Tomie, 1996) Specifically, the relevance of the hippocampus for path integration was demonstrated by random and inaccurate homing responses of rats with lesions to the hippocampus (involving complete lesioning of the dorsal hippocampus, see Maaswinkel et al., 1999;Save et al., 2001) and fimbria-fornix (Whishaw & Gorny, 1999;Whishaw et al., 2001;Whishaw & Maaswinkel, 1998;Whishaw & Tomie, 1996). Unlike the control rats (with intact hippocampus) that found their way back to home locations under both light and dark (or blindfolded) conditions, both hippocampectomized rats (Maaswinkel et al., 1999) and fimbria-fornix-lesioned rats were found to return home successfully only when allothetic cues (i.e., visual and/or olfactory cues) were available (Whishaw et al., 2001;Whishaw & Gorny, 1999;Whishaw & Maaswinkel, 1998;Whishaw & Tomie, 1996). ...
Over the past 30 years, numerous neuroscientific studies involving both human and rodent subjects have investigated the brain regions and networks supporting path integration and sought to identify the underlying neural mechanisms. Although these studies contributed to an increased understanding of path integration, a full picture of the brain mechanisms supporting path integration remains wanting. Hence, the current review was conducted with the aim of presenting an overview of the most notable neuroscientific studies on visual path integration in humans, identifying the commonalities and discrepancies in their findings, and introducing fresh ideas for future research. Specifically, this review focused on studies performed with virtual simulations of the triangle/path completion task and addressed whether or not the hippocampal formation is necessary for human path integration. Based on findings that supported and contradicted the involvement of the hippocampal formation in path integration, it was proposed that the use of different path integration strategies may determine the extent to which the hippocampus and entorhinal cortex are engaged during human path integration. To this end, recent studies investigating the impact of different path integration strategies on behavioral performance and functional brain activity were discussed. Methodological concerns were raised with feasible recommendations for improving the experimental design of future strategy-focused human path integration studies, which can cover cognitive neuroscience research on age-related differences in the role of the hippocampal formation in path integration and Bayesian modeling of the interaction between landmark and self-motion cues. The practical value of investigating different path integration strategies was also discussed briefly from a biomedical perspective.
... Dead reckoning is now commonly referred to as path integration and has taken on a somewhat more restricted definition, focused primarily on the use of internally generated (idiothetic) neural signals ( Whishaw et al., 2001;Whishaw and Wallace, 2003;Etienne and Jeffery, 2004; Buzsáki 2005;McNaughton et al., 2006; Buzsáki and Moser, 2013; Chrastil 2013;Geva-Sagiv et al., 2015; Finkelstein et al., 2016; Igarashi 2016;Grieves and Jeffery, 2017;Moser et al., 2017). Mammals were first confirmed to utilize path integration in navigation nearly forty years ago (Mittelstaedt and Mittelstaedt, 1980), and multiple brain regions have since been implicated in this function ( McNaughton et al., 1996;Whishaw et al., 1997;Whishaw and Wallace, 2003; Eti- enne and Jeffery, 2004;Parron and Save, 2004;Nitz 2006;Wolbers et al., 2007;Moser et al., 2008;2017;Whitlock et al., 2012;Wilber et al., 2017). ...
... Dead reckoning is now commonly referred to as path integration and has taken on a somewhat more restricted definition, focused primarily on the use of internally generated (idiothetic) neural signals ( Whishaw et al., 2001;Whishaw and Wallace, 2003;Etienne and Jeffery, 2004;Buzsáki 2005;McNaughton et al., 2006;Buzsáki and Moser, 2013;Chrastil 2013;Geva-Sagiv et al., 2015;Finkelstein et al., 2016;Igarashi 2016;Grieves and Jeffery, 2017;Moser et al., 2017). Mammals were first confirmed to utilize path integration in navigation nearly forty years ago (Mittelstaedt and Mittelstaedt, 1980), and multiple brain regions have since been implicated in this function ( McNaughton et al., 1996;; Whishaw et al., 1997;Whishaw and Wallace, 2003;Eti- enne and Jeffery, 2004;Parron and Save, 2004;Nitz 2006;Wolbers et al., 2007;Moser et al., 2008;2017;Whitlock et al., 2012;Wilber et al., 2017). ...
A comprehensive review of the heavily interconnected neural circuitry that integrates speed and space in the brain. We start with the rate and temporal codes for speed in the hippocampus and work backwards towards both the motor and sensory systems. We also highlight the need for experiments that systematically attempt to differentiate the respective contributions of these inputs as well as emphasize the importance of high-resolution, precise tracking of the latency of speed-encoding compared to the actual change in speed to achieve this aim.
... This notion is strengthened by more recent evidence demonstrating that hippocampal damage selectively disrupts the ability to utilize distal cues, but spares navigation based on directional or heading vectors (Pearce et al., 1998). It is also possible that damageinduced performance deficits reflect a loss of acquired search strategy, thus precluding accomplishment of the WM task (Clark et al., 2007;Whishaw et al., 1997). Given that deficits depend on the magnitude and region of hippocampal damage along the septo-temporal axis (Bannerman et al., 1999;Richmond et al., 1999), both options seem plausible. ...
... Such behavior may persist for multiple trials in mice, while rats, on the other hand, rapidly alter their search strategies (Vorhees and Williams, 2006). Animals with hippocampal injury also spend an inordinate time searching in the quadrant where the platform was originally located (Whishaw et al., 1997). Over repeated exposures, the learning curve is often steeper than the original acquisition rate because animals have already learned to utilize visual cues and swim away from the pool wall (Terry, 2009). ...
... The objective of the present paper is to present further evidence from new spontaneous exploratory tasks and from new formal spatial tasks to show that the hippocampus plays a role in dead reckoning [52]. We will first provide some background on the kinds of cues and strategies that animals can use to navigate. ...
... To evaluate the contribution of the hippocampal formation to navigation, we damage the hippocampus by making selective cell-specific lesions in the hippocampus or by making lesions to its major pathways or allied structures [44][45][46][47][48][49][50][51][52][53][54][55]. In the present, studies we damaged the hippocampus by making cathodal electrolytic lesions in the fimbria-fornix, a main input pathway into the hippocampus (Fig. 2). ...
... However, it has recently been shown that the hippocampus is necessary for the ability of rats to use self-motion cues, or path integration, to guide their behavior and maintain orientation across environments (Golob & Taube, 1999;Maaswinkel, Jarrard, & Whishaw, 1999;Whishaw & Corny, 1999;Whishaw, McKenna, & Maaswinkel, 1997). This finding is consistent with the conceptual model in which the hippocampus serves as a "path-integrator," maintaining a representation of the animal's location through integration of inertial information (McNaughton et al., 1996). ...
Rats were trained on a reinforced, delayed alternation T-maze task in the presence (cue group) or absence (no-cue group) of salient extramaze landmarks. A surprising finding was that the acquisition and memory performance of the 2 groups did not differ. Manipulations of the extramaze landmarks for the cue group suggested that, although landmarks were used to guide behavior, other sources of information were also used normally. The no-cue group was able to perform the task at above-chance levels even when extramaze, intramaze, and inertial sources of orientation were manipulated. These results suggest that memory performance on the T maze does not rely exclusively on the processing of allocentric spatial relationships in the maze environment.
... In tasks that reward avoidance of a recently visited place, such as the radial maze task of Olton and Samuelson (1976) or rewarded alternation in a T maze, the memory of going to a place can cue the animal to avoid retracing its path. As previously noted, Whishaw and colleagues (Whishaw & Gorny, 1999;Whishaw & Maaswinkel, 1998;Whishaw, McKenna, & Maaswinkel, 1997) contend that hippocampal-system lesions produce deficits only in tasks for which idiothetic cues are important, not those for which allothetic cues are sufficient. By contrast, the task used in the present study is one in which idiothetic cues are relatively uninformative. ...
Hippocampal-lesioned rats (HPC) and sham controls (SH) learned constant-negative visual discriminations among scenes in a Y-maze. Any arm could be start arm for a trial. Two choice scenes (“constant” and “variable”) were shown in the other arms. In Experiment 1, each problem had 2 constants. One or the other constant appeared on every trial, and the variable changed every trial; choosing the variable was rewarded. There were 4 problem types. Each constant might be always in a given direction from the start arm (added egocentric [Ego] cue), always in a given maze arm (added allocentric [Allo] cue), both, or neither. SH rats' visual learning was enhanced by Ego and by Allo cues. HPC rats' visual learning was enhanced by Ego cues, and by Allo cues, but only if there was no Ego cue. Experiment 2 confirmed that Allo cues helped HPC rats as much as SH, in the absence of Ego cues. Rats with HPC lesions can learn about allocentric place cues when navigation and idiothetic cue control are not required.
... Spatial memory formation has been highly associated with hippocampal function (Morris et al., 1982;McNaughton et al., 1996). In the last decade, the involvement of the dorsal hippocampus in spatial learning and memory has been well documented (McNaughton et al., 1996;Bures et al., 1997;Whishaw et al., 1997). ...
Spatial memory has been strongly associated with hippocampal function. There are several reports of the participation of this structure in acquisition and consolidation of spatial tasks. In this study, we evaluated the effects of selective and non-selective muscarinic antagonists in the dorsal hippocampus of rats during acquisition and encoding of a spatial task. Rats were trained in a Morris water maze for 4 days with identical daily sessions, and tested for long-term memory (LTM) 1 week after training. The animals were injected bilaterally in the dorsal hippocampus 20 min before the start of every day of training. The results showed that the non-selective muscarinic antagonist, scopolamine, disrupted acquisition of water maze memory formation. Moreover, microinjections of a selective postsynaptic muscarinic antagonist, pirenzepine, disrupted LTM, whereas it did not affect acquisition. Conversely, a selective presynaptic muscarinic antagonist, AFDX-116, did not disrupt either water maze acquisition or LTM formation. Combination of AFDX-116 and pirenzepine had similar effects as scopolamine, partially blocking acquisition and impairing long-term spatial memory. These results support the view that muscarinic receptors are involved in spatial learning and that postsynaptic muscarinic receptors in the dorsal hippocampus are particularly involved in long-term spatial memory formation.
... Extensive study was undertaken to identify which environmental cues were used by the animal to recognize its spatial position, and whether activity of the place cells showed spatially selectivity when the animals were placed in a different environment [14,15]. Navigational problems were observed following hippocampal lesions [16,17]. Whether the mnemonic and spatial properties are functionally distinct or different facets of the same overarching function was a matter of debate, however, which continues to this day [18][19][20][21]. ...
Beyond its established role in declarative memory function, the hippocampus has been implicated in varied roles in sensory processing and cognition, particularly those requiring temporal or spatial context. Disentangling its known role in memory from other cognitive functions can be challenging, as memory is directly or indirectly involved in most conscious activities, including tasks that underlie most experimental investigations. Recent work from this lab has examined the directional influence from the hippocampus on cortical areas involved in task performance, including tasks requiring movements, sensory processing, or language judgments. The hippocampus shows preferential connectivity with relevant cortical areas, typically the region critically involved in task performance, raising the possibility that the hippocampus plays a role in cognitive control. Minimal criteria for a role in cognitive control are proposed, and hippocampal connectivity with sensorimotor cortex during a non-mnemonic motor task is shown to meet this standard. Future directions for exploration are discussed.
... For example, place cells have clearly demonstrated their essential roles in some memory-related tasks [68,69]. Also, our SFA model contains no recurrent connectivity [70] and path integration [71] mechanisms that are usually considered in theoretical hippocampal modelings. However, from a practical point of view, this simplicity also makes it outperform many other models in the way that it is convenient to model feature responses akin to those of hippocampal cell types in a real robotic context. ...
Extensive studies have shown that many animals’ capability of forming spatial representations for self-localization, path planning, and navigation relies on the functionalities of place and head-direction (HD) cells in the hippocampus. Although there are numerous hippocampal modeling approaches, only a few span the wide functionalities ranging from processing raw sensory signals to planning and action generation. This paper presents a vision-based navigation system that involves generating place and HD cells through learning from visual images, building topological maps based on learned cell representations and performing navigation using hierarchical reinforcement learning. First, place and HD cells are trained from sequences of visual stimuli in an unsupervised learning fashion. A modified Slow Feature Analysis (SFA) algorithm is proposed to learn different cell types in an intentional way by restricting their learning to separate phases of the spatial exploration. Then, to extract the encoded metric information from these unsupervised learning representations, a self-organized learning algorithm is adopted to learn over the emerged cell activities and to generate topological maps that reveal the topology of the environment and information about a robot’s head direction, respectively. This enables the robot to perform self-localization and orientation detection based on the generated maps. Finally, goal-directed navigation is performed using reinforcement learning in continuous state spaces which are represented by the population activities of place cells. In particular, considering that the topological map provides a natural hierarchical representation of the environment, hierarchical reinforcement learning (HRL) is used to exploit this hierarchy to accelerate learning. The HRL works on different spatial scales, where a high-level policy learns to select subgoals and a low-level policy learns over primitive actions to specialize on the selected subgoals. Experimental results demonstrate that our system is able to navigate a robot to the desired position effectively, and the HRL shows a much better learning performance than the standard RL in solving our navigation tasks.
... http://dx.doi.org/10.1101/465997 doi: bioRxiv preprint first posted online Nov. 8, 2018; influence both hippocampal place cells (Gothard, Skaggs, & McNaughton, 1996;Quirk, Muller, & Kubie, 1990) and entorhinal grid cells (Hafting, Fyhn, Molden, Moser, & Moser, 2005), and that lesions to HPC and ERC impair path integration performance (Parron & Save, 2004;Whishaw, McKenna, & Maaswinkel, 1997). ...
Spatial navigation can depend on path integration or environmental cues (e.g., landmarks), which are thought to be integrated in hippocampal and entorhinal circuits. This study investigates the anatomical basis of path integration and navigation based on a single local landmark using an individual differences approach, since people vary substantially in their ability to navigate with path integration cues and landmarks. In two experiments, we dissociated the use of path integration and a local landmark in the same navigation task, and investigated whether morphological variability in the hippocampus and entorhinal cortex could explain behavioral variability in young healthy humans. In Experiment 1, participants navigated in a fully immersive virtual reality environment, with body-based cues available for path integration. The participants first walked through a series of posts before attempting to walk back to the remembered location of the first post. We found that gray matter volume of the hippocampus positively predicted behavioral accuracy of retrieving the distance from the target to the local landmark. Hippocampus also positively predicted path integration performance in terms of walking-distance to the target location. Experiment 2 was conducted in a desktop virtual environment, with no body-based cues available. Optic flow served as path integration cues, and participants were tested on their memory of a learned target location along a linear track. Consistent with Experiment 1, the results showed that hippocampal volume positively predicted performance on the distance from the target to the local landmark. In contrast to Experiment 1, there was no correlation between hippocampal volume and path integration performance. Together, our two experiments provide novel and converging evidence that the hippocampus plays an important role in encoding egocentric distance to a single local landmark during navigation, and they suggest a stronger hippocampal involvement when path integration is based on body-based compared to optic flow cues.
... Functional imaging studies have demonstrated that hippocampal activity predicts accuracy in navigation in sparse environments (Wolbers et al., 2007;Sherrill et al., 2013), and PHC activity has also been observed during path integration (Sherrill et al., 2013). Lesions of the hippocampus and entorhinal cortex have been shown to cause impairments of path integration in rodents (Whishaw et al., 1997;McNaughton et al., 2006;Brun et al., 2008). BOLD activity in the hippocampus, PHC and RSC increases with Euclidean distance from the home location and with increased translation and rotation during virtual self-motion (Chrastil et al., 2015(Chrastil et al., , 2016, suggesting that these regions support path integration. ...
Humans differ in their individual navigational performance, in part because successful navigation relies on several diverse abilities. One such navigational capability is path integration, the updating of position and orientation during movement, typically in a sparse, landmark-free environment. This study examined the relationship between path integration abilities and functional connectivity to several canonical intrinsic brain networks. Intrinsic networks within the brain reflect past inputs and communication as well as structural architecture. Individual differences in intrinsic connectivity have been observed for common networks, suggesting that these networks can inform our understanding of individual spatial abilities. Here, we examined individual differences in intrinsic connectivity using resting state magnetic resonance imaging (rsMRI). We tested path integration ability using a loop closure task, in which participants viewed a single video of movement in a circle trajectory in a sparse environment, and then indicated whether the video ended in the same location in which it started. To examine intrinsic brain networks, participants underwent a resting state scan. We found that better performance in the loop task was associated with increased connectivity during rest between the central executive network (CEN) and posterior hippocampus, parahippocampal cortex (PHC) and entorhinal cortex. We also found that connectivity between PHC and the default mode network (DMN) during rest was associated with better loop closure performance. The results indicate that interactions between medial temporal lobe (MTL) regions and intrinsic networks that involve prefrontal cortex (PFC) are important for path integration and navigation.
... There are two neuronal substrates, which are proposed to integrate spatial signals and velocity-dependent theta oscillations: hippocampal place cells and entorhinal grid cells. Successful path integration depends on hippocampal (Whishaw et al., 1997(Whishaw et al., , 2001 and entorhinal areas Knierim et al., 2013), where the dysfunction of these limbic structures impairs motion-based navigation. The phase of the neuronal spikes of hippocampal place cells within the theta cycle correlates with the spatial location of the animal and the duration of the path (O' Keefe and Recce, 1993;Harris et al., 2002;Mehta et al., 2002). ...
Several cortical and diencephalic limbic brain regions incorporate neurons that fire in correlation with the speed of whole-body motion, also known as linear velocity. Besides the field mapping and head-directional information, the linear velocity is among the major signals that guide animal’s spatial navigation. Large neuronal populations in the same limbic regions oscillate with theta rhythm during spatial navigation or attention episodes; and the frequency of theta also correlates with linear velocity. A functional similarity between these brain areas is that their inactivation impairs the ability to form new spatial memories; whereas an anatomical similarity is that they all receive projections from medial septum-diagonal band of Broca complex. We review recent findings supporting the model that septal theta rhythm integrates different sensorimotor signals necessary for spatial navigation. The medial septal is described here as a circuitry that mediates experience-dependent balance of sustained attention and path integration during navigation. We discuss the hypothesis that theta rhythm serves as a key mechanism for the aligning of intrinsic spatial representation to: (1) rapid change of position in the spatial environment; (2) continuous alteration of sensory signals throughout navigation; and (3) adapting levels of attentional behavior. The synchronization of these spatial, somatosensory and neuromodulatory signals is proposed here to be anatomically and physiologically mediated by the medial septum.
... We propose that hippocampal rats have an impairment in using self-movement cues (idiothetic cues) and path integration (Whishaw et al. 1997). To know where they came from, animals can make a record of their own movements and then integrate that record to link the starting point to the goal. ...
... This information can be combined to update spatial position during navigation Erdem and Hasselmo, 2012;Hasselmo, 2009]. Lesion studies have yielded inconsistent results leading to controversy regarding the role of the hippocampus in path integration; some studies demonstrate that lesions to the hippocampus and entorhinal cortex cause impairments of path integration in rodents and humans [Brun et al., 2008;McNaughton et al., 2006;Philbeck et al., 2004;Whishaw et al., 1997;Worsley, 2001;Yamamoto et al., 2014], while other studies have shown minimal path integration impairments with lesions [Alyan and McNaughton, 1999;Kim et al., 2013;Shrager et al., 2008], suggesting that further investigation into the contribution of the hippocampus to path integration is needed. ...
Path integration, the constant updating of the navigator's knowledge of position and orientation during movement, requires both visuospatial knowledge and memory. This study aimed to develop a systems-level understanding of human path integration by examining the basic building blocks of path integration in humans. To achieve this goal, we used functional imaging to examine the neural mechanisms that support the tracking and memory of translational and rotational components of human path integration. Critically, and in contrast to previous studies, we examined movement in translation and rotation tasks with no defined end-point or goal. Navigators accumulated translational and rotational information during virtual self-motion. Activity in hippocampus, retrosplenial cortex (RSC), and parahippocampal cortex (PHC) increased during both translation and rotation encoding, suggesting that these regions track self-motion information during path integration. These results address current questions regarding distance coding in the human brain. By implementing a modified delayed match to sample paradigm, we also examined the encoding and maintenance of path integration signals in working memory. Hippocampus, PHC, and RSC were recruited during successful encoding and maintenance of path integration information, with RSC selective for tasks that required processing heading rotation changes. These data indicate distinct working memory mechanisms for translation and rotation, which are essential for updating neural representations of current location. The results provide evidence that hippocampus, PHC, and RSC flexibly track task-relevant translation and rotation signals for path integration and could form the hub of a more distributed network supporting spatial navigation. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
... Results have shown that the amount of shift in the cell's preferred direction between the familiar and novel environments was much greater in animals with lesions of the PoS or hippocampus than in intact animals (Goodridge and Taube, 1997;Golob and Taube, 1999). These results suggest that both the PoS and the hippocampus are involved in path integration mechanisms that enable an animal to maintain an accurate spatial representation between two contiguous environments, and are consistent with recent hypotheses that the hippocampus is important for the utilization of idiothetic-based cues during navigation (McNaughton et al., 1996;Whishaw et al., 1997;cf., Alyan et al., 1999). ...
Other portions of this volume provide a description of the fundamental properties of Head Direction (HD) cells and the brain structures that are important in processing this directional coding (see the Preface and Chapter 9). This chapter focuses on the types of sensory information that affect HD cell activity. We first consider how cues external to the body can affect HD cell discharge and then discuss the efficacy of cues derived from the body’s movements (i.e., those involved in path integration; see Chapter 9). We then discuss experiments that have examined how HD cells respond when these two types of information come in conflict with one another. Because many animals function in a three-dimensional environment, we’ll also describe studies that have examined HD cell activity when the animal is in different earth-centered planes. Finally, we conclude by discussing experiments that have explored the development of cue control and spatial orientation as it relates to HD cells.
... Behavioral studies in rats revealed that the hippocampal formation is involved in a form of navigation or ''path integration'' (e.g., Foster et al., 1989;McNaughton et al., 1995McNaughton et al., , 1996 in which an animal can determine spatial orientation (starting position, destination, and present location) based upon information from self-motion, even in the absence of external cues (e.g., Mittelsteadt and Mittelsteadt, 1980;Whishaw et al., 1997). Path integration is disrupted after lesions of the fimbriafornix (Whishaw and Maaswinkel, 1998) and activity of hippocampal neurons can depend on selfmotion cues (Foster et al., 1989). ...
... Behavioral studies in rats revealed that the hippocampal formation is involved in a form of navigation or ''path integration'' (e.g., Foster et al., 1989;McNaughton et al., 1995McNaughton et al., , 1996 in which an animal can determine spatial orientation (starting position, destination, and present location) based upon information from self-motion, even in the absence of external cues (e.g., Mittelsteadt and Mittelsteadt, 1980;Whishaw et al., 1997). Path integration is disrupted after lesions of the fimbriafornix (Whishaw and Maaswinkel, 1998) and activity of hippocampal neurons can depend on selfmotion cues (Foster et al., 1989). ...
... Behavioral studies in rats revealed that the hippocampal formation is involved in a form of navigation or ''path integration'' (e.g., Foster et al., 1989;McNaughton et al., 1995McNaughton et al., , 1996 in which an animal can determine spatial orientation (starting position, destination, and present location) based upon information from self-motion, even in the absence of external cues (e.g., Mittelsteadt and Mittelsteadt, 1980;Whishaw et al., 1997). Path integration is disrupted after lesions of the fimbriafornix (Whishaw and Maaswinkel, 1998) and activity of hippocampal neurons can depend on selfmotion cues (Foster et al., 1989). ...
... Behavioral studies in rats revealed that the hippocampal formation is involved in a form of navigation or ''path integration'' (e.g., Foster et al., 1989;McNaughton et al., 1995McNaughton et al., , 1996 in which an animal can determine spatial orientation (starting position, destination, and present location) based upon information from self-motion, even in the absence of external cues (e.g., Mittelsteadt and Mittelsteadt, 1980;Whishaw et al., 1997). Path integration is disrupted after lesions of the fimbriafornix (Whishaw and Maaswinkel, 1998) and activity of hippocampal neurons can depend on selfmotion cues (Foster et al., 1989). ...
... Behavioral studies in rats revealed that the hippocampal formation is involved in a form of navigation or ''path integration'' (e.g., Foster et al., 1989;McNaughton et al., 1995McNaughton et al., , 1996 in which an animal can determine spatial orientation (starting position, destination, and present location) based upon information from self-motion, even in the absence of external cues (e.g., Mittelsteadt and Mittelsteadt, 1980;Whishaw et al., 1997). Path integration is disrupted after lesions of the fimbriafornix (Whishaw and Maaswinkel, 1998) and activity of hippocampal neurons can depend on selfmotion cues (Foster et al., 1989). ...
... The MWM has been introduced as an instrument with particular sensitivity to investigate the effects of hippocampal lesions in rats[122]. Many authors have presented evidence for the specific and disproportionate involvement of hippocampal formation in the spatial aspects of MWM learn- ing[123]. Thus, it has been shown that hippocampuslesioned rats display impaired learning in hidden-but not in visible-platform MWM learning. ...
Dementia is a clinical syndrome with abnormal degree of memory loss and impaired ability to recall events from the past often characterized by Alzheimer's disease. The various strategies to treat dementia need validation of novel compounds in suitable animal models for testing their safety and efficacy. These may include novel anti-amnesic drugs derived from synthetic chemistry or those derived from traditional herbal sources. Multiple approaches have been adopted to create reliable animal models ranging from rodents to non-human primates, where the animals are exposed to a predetermined injury or causing genetic ablation across specific regions of brain suspected to affect learning functions. In this review various animal models for Alzheimer's disease and treatment strategies in development of anti dementia drugs are discussed and an attempt has been made to provide a comprehensive report of the latest developments in the field.
... Rats can use one or more of several different search strategies in order to navigate to the hidden platform in the water-maze task. These strategies include piloting (Prados & Trobalon, 1998), path integration (Benhamou, 1997;McNaughton, Chen, & Markus, 1991;Save, 1997;Whishaw, McKenna, & Maaswinkel, 1997), and beacon homing (this may have occurred in Eichenbaum, Stewart, & Morris, 1990). It is also apparent that rats will adopt search strategies that result in an increase in path sinuosity, thereby intensifying the search around the target, once they are near the platform location. ...
In order to compare the relative involvement of prefrontal and temporal regions in spatial memory, rats with bilateral electrolytic lesions of perirhinal cortex, prefrontal cortex, or both regions were tested in the water and radial-arm maze. Perirhinal and prefrontal lesions produced similar performance deficits during water-maze acquisition and in the radial-maze procedure. Perirhinal cortex lesions also disrupted performance in a water- maze probe trial conducted 5 min after four training trials, whereas prefrontal lesions did not. Surprisingly, the combined-lesion group was not impaired during water-maze acquisition and performed significantly better than the perirhinal-lesioned group in the probe trial. This finding is interpreted in terms of the executive function of prefrontal cortex and its possible role in switching behavior between different search strategies, only some of which may be dependent on perirhinal cortex.
... Path integration is the ability to keep track of changes in orienta- tion and position during movement through monitoring self-motion ( Etienne and Jeffery, 2004;Wolbers et al., 2007). Path integration is a crucial ability for the formation of cognitive maps (Etienne and Jeffery, 2004) and has been shown to be associated with hippocampal function ( Whishaw et al., 1997;Wolbers et al., 2007). In the path in- tegration task, participants saw a virtual desert (uniform surface without landmarks) on a computer screen. ...
... Many researchers have argued that allocentric spatial coding and/or a record of the subject's own movements through space (path integration) are central components in the hippocampal influence on spatial learning (Mc-NaUghton et aI., 1996;Morris, Garrud, Rawlins, & O'Keefe, 1982;O'Keefe & Nadel, 1978;Whishaw, McKenna, & Maaswinkel, 1997). D. Gaffan (in press) has recently proposed that idiothetic cues generated by self-movementwhether of the whole body, limbs, or eyes-could, in theory, participate in object-in-place memory, as he has defined it in monkeys and people. ...
We studied the perception of simple computer-generated scenes by normal and fornix-transected Dark Agouti rats. In Experiment 1, the rats were rewarded for approaching trial-unique variable scenes differing from a constant scene that was the same across trials (constant-negative paradigm). The groups performed equivalently when scenes differed only in their objects or only in the occupied positions; however, when two scenes shared an object- place combination, the normal rats were more likely to see them as similar than were the fornix-transected rats. In Experiment 2, the rats learned to discriminate pairs of scenes. Again, there was no lesion effect when scenes differed by a single cue, object or position, but when the two scenes comprised the same objects interchanged in position, fornix-transected rats learned relatively easily. Fornix transection reduces rats' sensitivity to object-place combinations within scenes, consistent with D. Gaffan's account of scene memory as an animal analogue of episodic memory deficits in amnesia.
... In agreement with this proposal, neuroimaging studies in 73 humans indicate an extensive overlap in the brain networks supporting episodic memory retrieval and navigation 74 (Buckner & Carroll, 2007; Hassabis & Maguire, 2007 ). Moreover, the hippocampo-entorhinal complex is involved in both pro- 75 cesses (Scoville & Milner, 1957; Squire, 1992; Whishaw, Hines, & Wallace, 2001; Whishaw & Jarrard, 1996; Whishaw & 76 Maaswinkel, 1998; Whishaw, McKenna, & Maaswinkel, 1997). Convergent issues from neuropsychological human studies 77 show that amnesic patients with hippocampal damages were deficient in integrating idiothetic cues (i.e., information 78 derived from the body movement; Gomez, Rousset, Bonniot, Charnallet, & Moreaud, 2014; Gomez et al., 2012; Philbeck, 79 Behrmann, Levy, Potolicchio, & Caputy, 2004; Worsley et al., 2001). ...
... Few experimental studies have linked PI to a specific brain structure, perhaps because PI most likely involves several processes including identifying an initial reference point, monitoring various idiothetic cue sources and computing current position (Taube (1999)). Several researchers have suggested that the hippocampus is the substrate for path integration (e.g., McNaughton et al. (1996); Samsonovich and McNaughton (1997); Whishaw et al. (1997)). Whilst it seems likely that path integration information is represented in the hippocampus, the lesion evidence does not appear to support the strong claim that the hippocampus is the path-integrator proper. ...
A consensus on how to characterise the anterograde and retrograde memory processes
that are lost or spared after hippocampal damage has not been reached. In
this thesis, I critically re-examine the empirical literature and the assumptions behind
current theories. I formulate a coherent view of what makes a task hippocampally dependent
at acquisition and how this relates to its long-term fate. Findings from a
neural net simulation indicate the plausibility of my proposals.
My proposals both extend and constrain current views on the role of the hippocampus
in the rapid acquisition of information and in learning complex associations.
In general, tasks are most likely to require the hippocampus for acquisition if
they involve rapid, associative learning about unfamiliar, complex, low salience stimuli.
However, none of these factors alone is sufficient to obligatorily implicate the
hippocampus in acquisition. With the exception of associations with supra-modal information
that are always dependent on the hippocampus, it is the combination of
factors that is important.
Detailed, complex information that is obligatorily hippocampally-dependent at
acquisition remains so for its lifetime. However, all memories are semanticised as
they age through the loss of detailed context-specific information and because generic
cortically-represented information starts to dominate recall. Initially hippocampally dependent
memories may appear to become independent of the hippocampus over
time, but recall changes qualitatively. Multi-stage, lifelong post-acquisition memory
processes produce semanticised re-representations of memories of differing specificity
and complexity, that can serve different purposes.
The model simulates hippocampal and cortical interactions in the acquisition and
maintenance of episodic and semantic events, and behaves in accordance with my
proposals. In particular, conceptualising episodic and semantic memory as representing
points on a continuum of memory types appears viable. Support is also found for
proposals on the relative importance of the hippocampus and cortex in the rapid acquisition
of information and the acquisition of complex multi-model information; and
the effect of existing knowledge on new learning. Furthermore, episodic and semantic
events become differentially dependent on cortical and hippocampal components.
Finally, as a memory ages, it is automatically semanticised and becomes cortically dependent.
... First, mIKKbKO mice spent significantly more time between releasing the lever and visiting the feeder than control or nIKKbKO mice when measured after the criterion was passed (Fig. 7E, **P 5 0.008; *P 5 0.032, Mann-Whitney test), suggesting that even though both knockout mice have learned to associate their action with the outcome to the same level as the controls, the navigation strategy of mIKKbKO and to a lesser extent of nIKKbKO mice was disturbed. This result is consistent with the observed disturbances in hippocampal fEPSPs in both groups, given the critical role of the hippocampus as a cognitive map and of hippocampal place cells in integration of signals deriving from translational and directional components of movements (Whishaw et al., 1997). ...
Microglia are CNS resident immune cells and a rich source of neuroactive mediators, but their contribution to physiological brain processes such as synaptic plasticity, learning, and memory is not fully understood. In this study, we used mice with partial depletion of IκB kinase β, the main activating kinase in the inducible NF-κB pathway, selectively in myeloid lineage cells (mIKKβKO) or excitatory neurons (nIKKβKO) to measure synaptic strength at hippocampal Schaffer collaterals during long-term potentiation (LTP) and instrumental conditioning in alert behaving individuals. Resting microglial cells in mIKKβKO mice showed less Iba1-immunoreactivity, and brain IL-1β mRNA levels were selectively reduced compared with controls. Measurement of field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the CA3-CA1 synapse in mIKKβKO mice showed higher facilitation in response to paired pulses and enhanced LTP following high frequency stimulation. In contrast, nIKKβKO mice showed normal basic synaptic transmission and LTP induction but impairments in late LTP. To understand the consequences of such impairments in synaptic plasticity for learning and memory, we measured CA1 fEPSPs in behaving mice during instrumental conditioning. IKKβ was not necessary in either microglia or neurons for mice to learn lever-pressing (appetitive behavior) to obtain food (consummatory behavior) but was required in both for modification of their hippocampus-dependent appetitive, not consummatory behavior. Our results show that microglia, through IKKβ and therefore NF-κB activity, regulate hippocampal synaptic plasticity and that both microglia and neurons, through IKKβ, are necessary for animals to modify hippocampus-driven behavior during associative learning. GLIA 2014
For decades, regulatory guidelines for safety assessment in rodents for drugs, chemicals, pesticides, and food additives with developmental neurotoxic potential have recommended a single test of learning and memory (L&M). In recent years some agencies have requested two such tests. Given the importance of higher cognitive function to health, and the fact that different types of L&M are mediated by different brain regions assessing higher functions represents a step forward in providing better evidence-based protection against adverse brain effects. Given the myriad of tests available for assessing L&M in rodents this leads to the question of which tests best fit regulatory guidelines. To address this question, we begin by describing the central role of two types of L&M essential to all mammalian species and the regions/networks that mediate them. We suggest that the tests recommended possess characteristics that make them well suited to the needs in regulatory safety studies. By brain region, these are (1) the hippocampus and entorhinal cortex for spatial navigation, which assesses explicit L&M for reference and episodic memory and (2) the striatum and related structures for egocentric navigation, which assesses implicit or procedural memory and path integration. Of the tests available, we suggest that in this context, the evidence supports the use of water mazes, specifically, the Morris water maze (MWM) for spatial L&M and the Cincinnati water maze (CWM) for egocentric/procedural L&M. We review the evidentiary basis for these tests, describe their use, and explain procedures that optimize their sensitivity.
Discoveries of functional cell types, exemplified by the cataloging of spatial cells in the hippocampal formation, are heralded as scientific breakthroughs. We question whether the identification of cell types based on human intuitions has scientific merit and suggest that "spatial cells" may arise in non-spatial computations of sufficient complexity. We show that deep neural networks (DNNs) for object recognition, which lack spatial grounding, contain numerous units resembling place, border, and head-direction cells. Strikingly, even untrained DNNs with randomized weights contained such units and support decoding of spatial information. Moreover, when these "spatial" units are excluded, spatial information can be decoded from the remaining DNN units, which highlights the superfluousness of cell types to spatial cognition. Now that large-scale simulations are feasible, the complexity of the brain should be respected and intuitive notions of cell type, which can be misleading and arise in any complex network, should be relegated to history.
Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark.
Rats with bilateral ibotenic acid lesions centered on the pre- and parasubiculum and control rats were tested in a series of spatial memory and object recognition memory tasks. Lesioned rats were severely impaired relative to controls in both the reference and working memory versions of the water maze task and displayed a delay-dependent deficit in a delayed nonmatch to place procedure conducted in the T-maze. Lesioned rats also displayed reduced exploration in a novel environment, and performance was altered in an object recognition procedure as compared with the control group. These findings indicate that the pre- and parasubiculum plays an important role in the processing of both object recognition and spatial memory.
Ants who have successfully navigated the long distance between their foraging spot and their nest dozens of times will drastically overshoot their destination if the size of their legs is doubled by the addition of stilts. This observation reflects a navigational strategy called path integration, a strategy also utilized by mammals. Path integration necessitates that animals keep track of their movement speed and use it to precisely and instantly modify where they think they are and where they want to go. Here we review the neural circuitry that has evolved to integrate speed and space. We start with the rate and temporal codes for speed in the hippocampus and work backwards towards the motor and sensory systems. We highlight the need for experiments designed to differentiate the respective contributions of motor efference copy versus sensory inputs. In particular, we discuss the importance of high-resolution tracking of the latency of speed-encoding as a precise way to disentangle the sensory versus motor computations that enable successful spatial navigation at very different speeds.
Spatial navigation is a universal behavior that varies depending on goals, experience and available sensory stimuli. Spatial navigational tasks are routinely used to study learning, memory and goal-directed behavior, in both animals and humans. One popular paradigm for testing spatial memory is the Morris water maze, where subjects learn the location of a hidden platform that offers escape from a pool of water. Researchers typically express learning as a function of the latency to escape, though this reveals little about the underlying navigational strategies. Recently, a number of studies have begun to classify water maze search strategies in order to clarify the precise spatial and mnemonic functions of different brain regions, and to identify which aspects of spatial memory are disrupted in disease models. However, despite their usefulness, strategy analyses have not been widely adopted due to the lack of software to automate analyses. To address this need we developed Pathfinder, an open source application for analyzing spatial navigation behaviors. In a representative dataset, we show that Pathfinder effectively characterizes the development of highly-specific spatial search strategies as male and female mice learn a standard spatial water maze. Pathfinder can read data files from commercially- and freely-available software packages, is optimized for classifying search strategies in water maze paradigms, and can also be used to analyze 2D navigation by other species, and in other tasks, as long as timestamped xy coordinates are available. Pathfinder is simple to use, can automatically determine pool and platform geometry, generates heat maps, analyzes navigation with respect to multiple goal locations, and can be updated to accommodate future developments in spatial behavioral analyses. Given these features, Pathfinder may be a useful tool for studying how navigational strategies are regulated by the environment, depend on specific neural circuits, and are altered by pathology.
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.
Humans differ in their individual navigational abilities. These individual differences may exist in part because successful navigation relies on several disparate abilities, which rely on different brain structures. One such navigational capability is path integration, the updating of position and orientation, in which navigators track distances, directions, and locations in space during movement. Although structural differences related to landmark-based navigation have been examined, gray matter volume related to path integration ability has not yet been tested. Here, we examined individual differences in two path integration paradigms: (1) a location tracking task and (2) a task tracking translational and rotational self-motion. Using voxel-based morphometry, we related differences in performance in these path integration tasks to variation in brain morphology in 26 healthy young adults. Performance in the location tracking task positively correlated with individual differences in gray matter volume in three areas critical for path integration: the hippocampus, the retrosplenial cortex, and the medial prefrontal cortex. These regions are consistent with the path integration system known from computational and animal models and provide novel evidence that morphological variability in retrosplenial and medial prefrontal cortices underlies individual differences in human path integration ability. The results for tracking rotational self-motion—but not translation or location—demonstrated that cerebellum gray matter volume correlated with individual performance. Our findings also suggest that these three aspects of path integration are largely independent. Together, the results of this study provide a link between individual abilities and the functional correlates, computational models, and animal models of path integration.
Memory is one of the most studied cognitive abilities. Episodic memory, the capacity to remember personal experiences, has unquestionably increased the survival fitness of mammalian species, including humans. In fact, as animals live in a dynamic environment, the memory for unique experiences, organized in both space and time, has presumably evolved to complement other types of memories that are specialized in extracting generalities from multiple experiences. Here, we seek to review the behavioral approaches used to investigate spatial, temporal, and episodic memory in mammals and to provide insight into the specific brain structures and potential neuronal mechanisms underlying these capacities.
The publication of a recent article in F1000Research has led to discussion of, and correspondence on a broader issue that has a long history in the fields of neuroscience and psychology. Namely, is it possible to separate the cognitive components of performance, in this case spatial behavior, from the motoric demands of a task? Early psychological experiments attempted such a dissociation by studying a form of spatial maze learning where initially rats were allowed to explore a complex maze, termed “latent learning,” before reinforcement was introduced. Those rats afforded the latent learning experience solved the task faster than those that were not, implying that cognitive map learning during exploration aided in the performance of the task once a motivational component was introduced. This form of latent learning was interpreted as successfully demonstrating that an exploratory cognitive map component was acquired irrespective of performing a learned spatial response under deprivation/motivational conditions. The neural substrate for cognitive learning was hypothesized to depend on place cells within the hippocampus. Subsequent behavioral studies attempted to directly eliminate the motor component of spatial learning by allowing rats to passively view the distal environment before performing any motor response using a task that is widely considered to be hippocampal-dependent. Latent learning in the water maze, using a passive placement procedure has met with mixed results. One constraint on viewing cues before performing a learned swimming response to a hidden goal has been the act of dynamically viewing distal cues while moving through a part of the environment where an optimal learned spatial escape response would be observed. We briefly review these past findings obtained with adult animals to the recent efforts of establishing a “behavioral topology” separating cognitive-spatial learning from tasks differing in motoric demands in an attempt to define when cognitive-spatial behavior emerges during development.
This chapter reviews evidence for the multiple parallel memory systems hypothesis: the idea that different kinds of information are processed and stored in anatomically distinct brain systems. The historical development of evidence that several different kinds of information are learned and are selectively affected by damage to different brain areas is reviewed. Current evidence is described for the existence of memory for three different kinds of information that are processed and stored in three different, independently functioning neural systems in rats and humans. Evidence for cooperation and competition among the systems for control of behavior suggests that they function independently and in parallel.
To assess the working memory system for egocentric distance and place information, delayed matching-to-sample (DMTS) go/no-go tasks were run for each rat. To assess the reference memory system, and to serve as a control for nonmemory deficits, successive discrimination go/no-go tasks were then conducted using the same rats. Rats with hippocampal, but not parietal cortex, lesions were impaired relative to controls in the working memory (DMTS) task for both egocentric distance and place information, although the deficit observed in the working memory task for egocentric distance information by rats with hippocampal lesions was mild. Neither hippocampal nor parietal cortex lesioned rats were impaired relative to controls in the reference memory (successive discrimination) task for either cue. The hippocampus appears to be involved in working memory for egocentric distance and in spatial location information, whereas the parietal cortex is not.
Unlabelled:
Path integration, the updating of position and orientation during movement, often involves tracking a home location. Here, we examine processes that could contribute to successful location tracking in humans. In particular, we investigate a homing vector model of path integration, whereby a navigator continuously tracks a trajectory back to the home location. To examine this model, we developed a loop task for fMRI, in which participants viewed movement that circled back to a home location in a sparse virtual environment. In support of a homing vector system, hippocampus, retrosplenial cortex, and parahippocampal cortex were responsive to Euclidean distance from home. These results provide the first evidence of a constantly maintained homing signal in the human brain. In addition, hippocampus, retrosplenial cortex, and parahippocampal cortex, as well as medial prefrontal cortex, were recruited during successful path integration. These findings suggest that dynamic processes recruit hippocampus, retrosplenial cortex, and parahippocampal cortex in support of path integration, including a homing vector system that tracks movement relative to home.
Significance statement:
Path integration is the continual updating of position and orientation during navigation. Animal studies have identified place cells and grid cells as important for path integration, but underlying models of path integration in humans have rarely been studied. The results of our novel loop closure task are the first to suggest that a homing vector tracks Euclidean distance from the home location, supported by the hippocampus, retrosplenial cortex, and parahippocampal cortex. These findings suggest a potential homing vector mechanism supporting path integration, which recruits hippocampus and retrosplenial cortex to track movement relative to home. These results provide new avenues for computational and animal models by directing attention to homing vector models of path integration, which differ from current movement-tracking models.
Jean Piaget accorded the adaptive role of acting on objects in the formation of logical structures a priority during development. According to his studies, correspondence between the structure of spatial behavior in infants and mathematical properties of “group of displacements” implies the development of such logical constructs even before the appearance of language. In the present analysis, it will be demonstrated that such mathematical structures can also be inferred from spatial behavior of the rat (Rattus Norvegicus) and some other species. However, despite such correspondence, there are dissimilarities in the performance of different species. Such similarities and differences will be discussed in relation to the formation of abstract processes and cognitive competence across species. The analysis supports the philosophical notion that different phenomena may have parallel mathematical descriptions but whether or not they are the same always has to be examined at the conceptual level as well.
Improvement on spatial tasks is observed during a late, postnatal developmental period (PND18 – PND24). The purpose of the current work was 1) to determine whether the emergence of spatial-behavioral function was based on the ability to generate appropriate behavioral output; 2) to assess whether mossy fiber connectivity patterns preceded the emergence of spatial-behavioral function; 3) to explore functional changes in the hippocampus to determine whether activity in hippocampal networks occurred in a training-dependent or developmentally-dependent fashion. To these ends, male, Long Evans rats were trained on a spatial water or dry maze task for one day (PND16, PND18 or PND20) then euthanized. Training on these 2 tasks with opposing behavioral demands (swimming versus exploration) was hypothesized to control for behavioral topology. Only at PND20 was there evidence of spatial-behavioral function for both tasks. Examination of synaptophysin staining in the CA3 region (i.e., mossy fiber projections) revealed enhanced connectivity patterns that preceded the emergence of spatial behavior. Analysis of c-Fos labeling (functional changes) revealed developmentally-dependent increases in c-Fos positive cells in the dentate gyrus, CA3 and CA1 regions whereas training-dependent increases were noted in the CA3 and CA1 regions for the water-maze trained groups. Results suggest that changes in mossy fiber connectivity in association with enhanced hippocampal functioning precede the emergence of spatial behavior observed at PND20. The combination of neuroanatomical and behavioural results confirms the hypothesis that this time represents a sensitive period for hippocampal development and modification and the emergence of spatial/ cognitive function.
The publication of a recent article in
F1000Research has led to discussion of, and correspondence on a broader issue that has a long history in the fields of neuroscience and psychology. Namely, is it possible to separate the cognitive components of performance, in this case spatial behavior, from the motoric demands of a task? Early psychological experiments attempted such a dissociation by studying a form of spatial maze learning where initially rats were allowed to explore a complex maze, termed “latent learning,” before reinforcement was introduced. Those rats afforded the latent learning experience solved the task faster than those that were not, implying that cognitive map learning during exploration aided in the performance of the task once a motivational component was introduced. This form of latent learning was interpreted as successfully demonstrating that an exploratory cognitive map component was acquired irrespective of performing a learned spatial response under deprivation/motivational conditions. The neural substrate for cognitive learning was hypothesized to depend on place cells within the hippocampus. Subsequent behavioral studies attempted to directly eliminate the motor component of spatial learning by allowing rats to passively view the distal environment before performing any motor response using a task that is widely considered to be hippocampal-dependent. Latent learning in the water maze, using a passive placement procedure has met with mixed results. One constraint on viewing cues before performing a learned swimming response to a hidden goal has been the act of dynamically viewing distal cues while moving through a part of the environment where an optimal learned spatial escape response would be observed. We briefly review these past findings obtained with adult animals to the recent efforts of establishing a “behavioral topology” separating cognitive-spatial learning from tasks differing in motoric demands in an attempt to define when cognitive-spatial behavior emerges during development.
Improvement on spatial tasks is observed during a late, postnatal developmental period (PND18 – PND24). The purpose of the current work was 1) to determine whether the emergence of spatial-behavioral function was based on the ability to generate appropriate behavioral output; 2) to assess whether mossy fiber connectivity patterns preceded the emergence of spatial-behavioral function; 3) to explore functional changes in the hippocampus to determine whether activity in hippocampal networks occurred in a training-dependent or developmentally-dependent fashion. To these ends, male, Long Evans rats were trained on a spatial water or dry maze task for one day (PND16, PND18 or PND20) then euthanized. Training on these 2 tasks with opposing behavioral demands (swimming versus exploration) was hypothesized to control for behavioral topology. Only at PND20 was there evidence of spatial-behavioral function for both tasks. Examination of synaptophysin staining in the CA3 region (i.e., mossy fiber projections) revealed enhanced connectivity patterns that preceded the emergence of spatial behavior. Analysis of c-Fos labeling (functional changes) revealed developmentally-dependent increases in c-Fos positive cells in the dentate gyrus, CA3 and CA1 regions whereas training-dependent increases were noted in the CA3 and CA1 regions for the water-maze trained groups. Results suggest that changes in mossy fiber connectivity in association with enhanced hippocampal functioning precede the emergence of spatial behavior observed at PND20. The combination of neuroanatomical and behavioural results confirms the hypothesis that this time represents a sensitive period for hippocampal development and modification and the emergence of spatial/ cognitive function.
Brains from PND16, PND18 and PND20 from home cage control (HCC), object in a novel location (ONL) or Morris water maze (MWM) groups were removed and processed immunohistochemically for synaptophysin staining in the CA3 region as a marker for MF connectivity. Left panels show representative staining from the three age groups (images from MWM condition). Abbreviations: SO: stratum oriens; SP: stratum pyramisale; SL: stratum lucidum. Arrows point to synaptophysin-positive puncta in the SO region. Scale bar = 100 µm. (A) Synaptophysin-positive puncta quantified in the SL region revealed a main effect of age with group PND16 showing more staining than PND18 and PND20 (*, p < 0.05). (B) Synaptophysin-positive puncta quantified in the SO region revealed a main effect of age with group PND18 showing more staining than PND16 (++, p < 0.01) and group PND20 showing more staining than groups PND16 and PND18 (**, p < 0.01). (C) Ratio of synaptophysin-positive puncta quantified in the SO: SL region (to control for potential size variation) revealed a main effect of age with group PND18 showing more staining than PND16 (++, p < 0.01) and group PND20 showing more staining then groups PND16 and PND18 (**, p < 0.01).
A large body of data now supports the view that portions of the septohip-pocampal system play a critical role in the modulation of specific memory processes in both people and animals (Squire 1992; von Cramon and Schuri 1992; Cohen and Eichenbaum 1993). In people, there is good evidence that the hippocampal system modulates declarative memory (Squire 1992; Cohen and Eichenbaum 1993), and other neural systems mediate nonde-clarative memory (Schacter, Chiu, and Ochsner 1993; Squire, Knowlton, and Musen 1993; Zola-Morgan and Squire 1993). In people, declarative memory can be defined as “the capacity for conscious recollections about facts and events,” and nondeclarative memory as “a heterogenous collection of non-conscious abilities that includes the learning of skills and habits” (Zola- Morgan and Squire 1993, p. 547). In addition, Mishkin et al. (1997) have argued that, in people, the semantic (facts) and episodic (events) components of declarative memory might be modulated by different portions of the hippocampal system, with the hippocampus proper playing a stronger role in the regulation of episodic memory, whereas the perirhinal and parahippocampal cortex more strongly mediate semantic memory. In that study, three patients who suffered relatively selective damage to the hippocampus proper early in life subsequently acquired a reasonable base of semantic knowledge, but evidenced severe impairments in episodic memory.
EILAM D. Of mice and men: Building blocks in cognitive mapping. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX - Exploration is the process by which humans and other animals gather spatial information and construct some representation of unfamiliar environments, and then utilize this information for traveling in those environments. This survey presents similarities in the travel paths of rodents and humans, suggesting that these constitute an expression of similar underlying biobehavioral mechanisms. Emphasis is given to exploration in dark or large environments, which one cannot encompass at a glance, necessitating a gradual sector-by-sector exploration. This is compared with exploration of the relatively small laboratory testing environments, where a condensed form of exploration dominates. In both rodents and humans, exploration culminates in free traveling, which is mainly determined by the physical environment. For this phase, some principles of urban design in humans and a reminiscent impact of landmarks in test environments in animals are compared. Finally, it is suggested that animal spatial behavior could provide insights into the way that humans perceive and conceive urban environments, and that spatial cognition in different animals, including humans, rests on an evolutionary analogy (or even homology).
New Zealand male rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink conditioning paradigm using a 250-ms tone conditioned stimulus, a 100-ms airpuff unconditioned stimulus, and a 500-ms trace interval. Rabbits received bilateral hippocampal aspirations either 1 day or 1 month after learning. Controls consisted of time-matched sham-operated and neocortical aspirated rabbits. When retested on the trace paradigm, rabbits with hippocampal aspirations 1 day after learning were significantly and substantially impaired in the retention of trace conditioned responses. In contrast, rabbits that received hippocampal aspirations 1 month after training retained trace conditioned responses at a level comparable to that of the controls. Moreover, hippocampectomy had no effect on the retention of delay eyeblink conditioning. Thus, the hippocampus appears to be necessary for the retention of recently acquired, but not remotely acquired, trace conditioned responses.
The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons, but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL, and ABL rats received ISC; neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus.
All mobile species have to solve spatial problems in order to be in the right place at the right time. Adaptive strategies
are developed at different levels, from the selection of a specific habitat to cognitive skills and specially developed brain
structures. All these levels are highly interactive and a comparative approach is an optimal tool for understanding brainenvironment-behaviour
interactions in spatial orientation.
This paper reviews spatial memory processes in three highly evolved taxa: hymenoptera, birds and mammals. In these three taxa, the goal location can be memorized egocentrically as a vector specifying the head-referred direction and the distance to the goal, and/or exocentrically as a view specifying the spatial layout of the surrounding landmarks perceived by the animal when standing at the goal. The egocentric coding process requires a path-integration mechanism to update the memorized goal location as a function of the animal's current position. Changes of direction are estimated allothetically (by reference to an external compass) in hymenoptera, idiothetically (on the basis of internal movement-related information) in mammals, and probably in both ways in birds. Computer simulations have shown that path-integration is very sensitive to random errors occurring in idiothetic but not in allothetic estimations. When using the exocentric coding process, hymenoptera store the bearings and angular sizes of landmarks in a compass-oriented colour snapshot taken at the goal. They may then return to the goal by moving so as to reduce the discrepancy between the current view of landmarks and the memorized snapshot. In mammals, this process can be accounted for by a neurobiologically plausible model which highlights the fundamental role of exploration of the environment. The way this process is implemented in birds is less clear.
Electrophysiological studies have shown that single cells in the
hippocampus respond during spatial learning and
exploration1-4, some firing only when animals enter specific
and restricted areas of a familiar environment. Deficits in spatial
learning and memory are found after lesions of the hippocampus and its
extrinsic fibre connections5,6 following damage to the medial
septal nucleus which successfully disrupts the hippocampal theta
rhythm7, and in senescent rats which also show a correlated
reduction in synaptic enhancement on the perforant path input to the
hippocampus8. We now report, using a novel behavioural
procedure requiring search for a hidden goal, that, in addition to a
spatial discrimination impairment, total hippocampal lesions also cause
a profound and lasting placenavigational impairment that can be
dissociated from correlated motor, motivational and reinforcement
aspects of the procedure.
Rats were trained on delayed matching-to-sample (DMS) with goalboxes containing complex objects as stimuli. On reaching the preoperative learning criterion, the rats were allocated to conventional fornix-lesioned or control groups. In a series of postoperative DMS experiments, different kinds of stimuli were used, ranging from complex object boxes to large, simple black or white goalboxes, with 3 transitional types in between. Lesions impaired choice accuracy whenever the rats were tested with large, simple goalboxes, but not with smaller boxes of otherwise identical construction. A brief, final experiment showed no amelioration of the lesion-induced impairment when complex objects were added to large, simple goalboxes. The results are discussed in terms of spatial and nonspatial accounts of hippocampal function.
Brain structures thought to be critical for learning and memory were lesioned, and the effects on rats' ability to locate food on a radial maze in situations that provided different types of information was used to suggest general principles of information processing by hypothesized neural systems that include each of the lesioned structures. When animals were confined to food-containing and empty arms on different training trials, the learned discrimination between the arms was amygdala based. More training trials were required for ambiguous (adjacent arms) than for unambiguous (widely separated arms) discriminations. When rats moved around and entered both food and no-food arms on the same trial, the unambiguous discrimination was learned by both dorsal striatum- and hippocampus-based systems; however, the ambiguous discrimination was learned only by the hippocampus system.
The effects of entorhinal cortex lesions, combined entorhinal and perirhinal cortex lesions, and fornix lesions on the conditioning of fear responses (freezing) to contextual stimuli were examined using a conditioning procedure known to produce hippocampal-dependent contextual conditioning. Lesions of the entorhinal and or entorhinal plus perirhinal cortex did not disrupt contextual conditioning, but lesions of the fornix did. None of the lesions affected conditioning to an explicit conditioned stimulus. Given that the entorhinal cortex is the primary linkage between the neocortex and the hippocampus and that the fornix is the primary linkage with subcortical structures, subcortical inputs to and outputs of the hippocampus appear to be sufficient to mediate contextual fear conditioning. As a result, the presumption that neocortical information is required for contextual fear conditioning, and perhaps other hippocampal-dependent functions, should be reevaluated.
Damage to the hippocampal system disrupts recent memory but leaves remote memory intact. The account presented here suggests that memories are first stored via synaptic changes in the hippocampal system, that these changes support reinstatement of recent memories in the neocortex, that neocortical synapses change a little on each reinstatement, and that remote memory is based on accumulated neocortical changes. Models that learn via changes to connections help explain this organization. These models discover the structure in ensembles of items if learning of each item is gradual and interleaved with learning about other items. This suggests that the neocortex learns slowly to discover the structure in ensembles of experiences. The hippocampal system permits rapid learning of new items without disrupting this structure, and reinstatement of new memories interleaves them with others to integrate them into structured neocortical memory systems.
Some theories of hippocampal formation function postulate that it is involved in using the relationships between distal cues for spatial navigation. That rats with damage to the hippocampal formation are impaired in learning place responses of escaping to a platform hidden just below the surface of the water of a swimming pool, supports this view. Using rats with fimbria-fornix (FF) lesions, we examined whether their impairment is related to an inability to learn how to reach the platform as opposed to learning its location. In a first experiment, the FF rats were impaired in learning to swim to a hidden platform but could swim to a visible platform. In a second experiment, after being pretrained to swim to a visible platform, the FF rats swam to, paused, and searched the vicinity of the platform's previous location when it was removed. This finding showed that the FF rats expected to find the platform at that location. Additional tests confirmed that they had learned a place response. Despite having acquired a place response, they still could not acquire new place responses when only the hidden platform training procedure was used. Thus, these results in dissociating the processes of "getting there" and "knowing where" suggest that the FF rats' impairment may be in some process of motoric control, such as path integration, rather than in learning the location of the platform in relation to ambient cues. The results are discussed in relation to relevant theories of hippocampal function.
Monkeys with bilateral lesions of the CA1 field of the hippocampus produced by the injection of neurotoxin diagonally along the length of the hippocampus were found to have a severe impairment on the retention of a conditional task learnt prior to surgery and on the new acquisition of several types of this task. They were equally impaired on conditional tasks that required a spatial response or an object choice in response to either visual or spatial cues. They were not impaired on simple visual discrimination tasks, simple spatial discrimination tasks or reversal learning of these tasks. This patterns of impairment resembles that seen in the same species with neurotoxic lesions within the vertical limb of the diagonal band of Broca or transection of the fornix. Monkeys with subtotal lesions of the adjacent medial temporal area were not consistently impaired on any of these tasks. The results suggest that hippocampal lesions produce anterograde and retrograde amnesia for information other than reward association.
Vicarious trial-and-error (VTE) is a term that Muenzinger and Tolman used to describe the rat's conflict-like behavior before responding to choice. Recently, VTE was proposed as a mechanism alternative to the concept of "cognitive map" in accounts of hippocampal function. That is, many phenomena of impaired learning and memory related to hippocampal interventions may be explained by behavioral first principles: reduced conflicting, incipient, pre-choice tendencies to approach and avoid. The nonspatial black-white discrimination learning and VTE behavior of the rat were investigated. Hippocampal-lesioned and sham-lesioned animals were trained for 25 days (20 trials per day) starting at 60 days of age. Each movement of the head from one discriminative stimulus to the other was counted as a VTE instance. Lesioned rats had fewer VTEs than sham controls, and the former learned much more slowly or never learned. After learning, VTE frequency declined. Male and female rats showed no significant differences in VTE behavior or discrimination learning.
Hippocampal place cells show location-specific firing as animals locomote in an environment. A possible explanation for these place fields is that each cell is simply driven by environmental sensory inputs available in its field. This cannot provide the full explanation, however, since cells can maintain stable place fields even in the absence of reliable environmental orienting cues. This suggests the cells are also influenced by movement-related information, since this is the only available, ongoing indicator of current location when external orienting cues are not present. Two candidates for the movement-related information are vestibular activation, and visual motion. To test for these influences, place cells were recorded as animals locomoted in a cylindrical apparatus that was made so that its wall (painted with vertical black and white stripes) and floor could be independently rotated, to provide visual motion and vestibular inputs, respectively. The results showed that both these inputs could influence place fields. Sometimes they caused a predictable locational shift, so that the field rotated its location on the apparatus floor in a way that was compatible with the movement indicated by the vestibular and/or visual motion input. This updating was most reliably obtained when the two inputs were presented in combination. In other cases, the apparatus rotations caused unpredictable changes in firing characteristics, so that cells either stopped firing, or developed place fields that were altered in overall size, shape, and eccentricity. Interestingly, the probability of these changes increased with experience with the rotational manipulations, suggesting a learned component.
Olfactory memory in control rats and in animals with entorhinal cortex lesions was tested in four paradigms: (1) a known correct odor was present in a group of familiar but nonrewarded odors, (2) six known correct odors were simultaneously present in a maze, (3) correct responses required the learning of associations between odors and objects, and (4) six odors, each associated with a choice between two objects, were presented simultaneously. Control rats had no difficulty with the first problem and avoided repeating selections in the second; this latter behavior resembles that reported for spatial mazes but, in the present experiments, was not dependent upon memory for the configuration of pertinent cues. Control animals varied considerably in their acquisition of odor-object associations with only a subgroup learning every set of pairings. These latter animals also performed well in the fourth task and, as indicated by post hoc analyses, developed complex strategies in dealing with the problem of serial odor-object pairs. Lesioned animals had no difficulty in selecting correct odors learned prior to surgery (problem one) but repeated their choices in problem two. This latter result suggests that hippocampus contributes to the transient memory of prior choices for odors as it does for prior choices in spatial mazes. Entorhinal rats were able to form odor-object associations (problem three), and a subgroup of the animals periodically succeeded in doing a long series of such choices (problem four), though with less frequency than controls. These results indicate that rats use both long-term memory and transient memory in dealing with olfactory problems and suggest that the second of these is dependent upon a hippocampal process that encodes a type of information other than the relationship between cues.
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.
In gross anatomical terms, the hippocampal archicortex can be conceived as an "appendage' of the large neocortex. In contrast to neocortical areas, the main output targets of the hippocampus are the same as its main inputs (i.e., the entorhinal cortex). Highly processed information about the external world (the content) reaches the hippocampus via the entorhinal cortex, whereas information about the "internal world' (the context) is conveyed by the subcortical inputs. Removal of the context makes the content illegible, as demonstrated by the observation that the behavioral impairment following surgical removal of hippocampopetal subcortical inputs is as devastating as removing the hippocampus itself. From its strategic anatomical position and input-output connections, it may be suggested that the main function of the hippocampal formation is to modify its inputs by feeding back a processed "reafferent copy' to the neocortex. I hypothesize that neocortico-hippocampal transfer of information and the modification process in neocortical circuitries by the hippocampal output take place in a temporally discontinuous manner and might be delayed by minutes, hours, or days. Acquisition of information may happen very fast during the activated state of the hippocampus associated with theta/gamma oscillations. Intrahippocampal consolidation and the hippocampal-neocortical transfer of the stored representations, on the other hand, is protracted and carried by discrete quanta of cooperative neuronal bursts during slow wave sleep.
Data from a large series of experiments on marmosets with lesions of the septal/diagonal band area (DB), fornix or CA1 area of the hippocampus are analysed in terms of retention of information learned before surgery, acquisition of new information and retention of information acquired after surgery. It is shown that although all three lesions impair acquisition of a specific type of new information, lesions of CA1 result in a severe retrograde amnesia but no forgetting of that type of information adequately acquired after surgery, whereas lesions of the DB do not cause retrograde amnesia but do result in significant forgetting. Monkeys with fornix transection occupied an intermediate position in their pattern of learning impairments; some animals showed evidence of forgetting, whereas the great majority showed retrograde amnesia. These data may be relevant to an understanding of the different extent of amnesia in patients with different pathology within the medial temporal lobe and associated subcortical structures.
The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons, but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL, and ABL rats received ISC; neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus.
Patient RB (Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus, S. Zola-Morgan, L. R. Squire, and D. G. Amaral, 1986, J Neurosci 6:2950-2967) was the first reported case of human amnesia in which detailed neuropsychological analyses and detailed postmortem neuropathological analyses demonstrated that damage limited to the hippocampal formation was sufficient to produce anterograde memory impairment. Neuropsychological and postmortem neuropathological findings are described here for three additional amnesic patients with bilateral damage limited to the hippocampal formation. Findings from these patients, taken together with the findings from patient RB and other amnesic patients, make three important points about memory. (1) Bilateral damage limited primarily to the CA1 region of the hippocampal formation is sufficient to produce moderately severe anterograde memory impairment. (2) Bilateral damage beyond, the CA1 region, but still limited to the hippocampal formation, can produce more severe anterograde memory impairment. (3) Extensive, temporally graded retrograde amnesia covering 15 years or more can occur after damage limited to the hippocampal formation. Findings from studies with experimental animals are consistent with the findings from amnesic patients. The present results substantiate the idea that severity of memory impairment is dependent on locus and extent of damage within the hippocampal formation and that damage to the hippocampal formation can cause temporally graded retrograde amnesia.
Rats were implanted chronically with hippocampal recording electrodes, a microinfusion guide cannula aimed at the medial septal nucleus, and an electrode for electrical stimulation of the posterior hypothalamic nucleus (PH). PH stimulation elicited running in rats placed in a wheel and simultaneously occurring hippocampal theta field activity (HPC-theta). In the preprocaine (PRE) testing condition, a positive linear relationship was demonstrated among the intensity of electrical stimulation of the PH, wheel-running speed, and the peak frequency of HPC-theta. HPC-theta amplitude reached an asymptote at the lowest levels of electrical stimulation of the PH. Procaine hydrochloride (1.5 microliters, 20% solution), a local anesthetic, was then infused into the medial septal nucleus (MS). Five minutes after the infusion, PH stimulation no longer induced wheel-running behavior or HPC-theta, and the remaining irregular field activity was significantly reduced in amplitude. Fifteen minutes after the procaine infusion, PH stimulation still did not elicit HPC-theta or running behavior in the majority of animals but did evoke large-amplitude sharp-waves. Thirty minutes after the procaine infusion, PH stimulation again elicited HPC-theta and running behavior, but HPC-theta peak frequency and running speeds were both significantly reduced compared with PRE values. Forty-five minutes after the infusion, HPC-theta amplitude had recovered to PRE values, but HPC-theta frequency and running speeds elicited by PH stimulation were still significantly reduced. By 60 min after procaine administration, the amplitude and frequency of HPC-theta and the running speeds elicited by PH stimulation recovered to PRE values. Multiple regression analysis revealed that the recovery pattern of running behavior reflected the frequency rather than the amplitude of HPC-theta. Neither saline control infusions into the MS nor procaine infusions into the lateral septum and paraventricular thalamic nucleus affected HPC-theta or running behavior. These findings are consistent with the notion that both the locomotor activity and "movement-related" HPC-theta frequency induced by electrically stimulating the PH were attributable to ascending activation of a hypothalamo-septal pathway and not to activation of descending brainstem or peripheral motor systems.
A theory of cognitive mapping is developed that depends only on accepted properties of hippocampal function, namely, long-term potentiation, the place cell phenomenon, and the associative or recurrent connections made among CA3 pyramidal cells. It is proposed that the distance between the firing fields of connected pairs of CA3 place cells is encoded as synaptic resistance (reciprocal synaptic strength). The encoding occurs because pairs of cells with coincident or overlapping fields will tend to fire together in time, thereby causing a decrease in synaptic resistance via long-term potentiation; in contrast, cells with widely separated fields will tend never to fire together, causing no change or perhaps (via long-term depression) an increase in synaptic resistance. A network whose connection pattern mimics that of CA3 and whose connection weights are proportional to synaptic resistance can be formally treated as a weighted, directed graph. In such a graph, a "node" is assigned to each CA3 cell and two nodes are connected by a "directed edge" if and only if the two corresponding cells are connected by a synapse. Weighted, directed graphs can be searched for an optimal path between any pair of nodes with standard algorithms. Here, we are interested in finding the path along which the sum of the synaptic resistances from one cell to another is minimal. Since each cell is a place cell, such a path also corresponds to a path in two-dimensional space. Our basic finding is that minimizing the sum of the synaptic resistances along a path in neural space yields the shortest (optimal) path in unobstructed two-dimensional space, so long as the connectivity of the network is great enough. In addition to being able to find geodesics in unobstructed space, the same network enables solutions to the "detour" and "shortcut" problems, in which it is necessary to find an optimal path around a newly introduced barrier and to take a shorter path through a hole opened up in a preexisting barrier, respectively. We argue that the ability to solve such problems qualifies the proposed hippocampal object as a cognitive map. Graph theory thus provides a sort of existence proof demonstrating that the hippocampus contains the necessary information to function as a map, in the sense postulated by others (O'Keefe, J., and L. Nadel. 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford, UK). It is also possible that the cognitive mapping functions of the hippocampus are carried out by parallel graph searching algorithms implemented as neural processes. This possibility has the great attraction that the hippocampus could then operate in much the same way to find paths in general problem space; it would only be necessary for pyramidal cells to exhibit a strong nonpositional firing correlate.
Animal models of amnesia have yielded many insights into the neural substrates of different types of memories. Some very important aspects of memory, however, have been ignored in research using experimental animals. For example, to examine long-term memory investigators traditionally have relied on measures of information acquisition, which stand in contrast to the measures of retention commonly used in work with humans. We have recently developed a behavioral paradigm that measures both the acquisition and long-term retention of object discriminations, and found a selective retention impairment in rats with entorhinal-hippocampal disconnection (Vnek et al., 1995). The present study was designed to determine whether direct damage to the hippocampus likewise would lead to a selective deficit in the retention of visual discriminations. Rats with aspiration lesions of the dorsal hippocampus, rats with neocortical control lesions, and normal controls were trained on three object discrimination problems and then retrained 3 weeks later to measure retention. All animals showed the same level of performance during the training (acquisition) phase of testing, but the performance of animals with dorsal hippocampal injury fell below that of controls during retraining (retention). Taken together, these and our earlier results suggest that the hippocampus and anatomically related structures are particularly important for retaining visual discriminations over long delay intervals. These findings may clarify the role of the hippocampus in nonspatial memory.
A theory of cognitive mapping is developed that depends only on accepted properties of hippocampal function, namely, long-term potentiation, the place cell phenomenon, and the associative or recurrent connections made among CA3 pyramidal cells. It is proposed that the distance between the firing fields of connected pairs of CA3 place cells is encoded as synaptic resistance (reciprocal synaptic strength). The encoding occurs because pairs of cells with coincident or overlapping fields will tend to fire together in time, thereby causing a decrease in synaptic resistance via long-term potentiation; in contrast, cells with widely separated fields will tend never to fire together, causing no change or perhaps (via long-term depression) an increase in synaptic resistance. A network whose connection pattern mimics that of CA3 and whose connection weights are proportional to synaptic resistance can be formally treated as a weighted, directed graph. In such a graph, a "node" is assigned to each CA3 cell and two nodes are connected by a "directed edge" if and only if the two corresponding cells are connected by a synapse. Weighted, directed graphs can be searched for an optimal path between any pair of nodes with standard algorithms. Here, we are interested in finding the path along which the sum of the synaptic resistances from one cell to another is minimal. Since each cell is a place cell, such a path also corresponds to a path in two-dimensional space. Our basic finding is that minimizing the sum of the synaptic resistances along a path in neural space yields the shortest (optimal) path in unobstructed two-dimensional space, so long as the connectivity of the network is great enough. In addition to being able to find geodesics in unobstructed space, the same network enables solutions to the "detour" and "shortcut" problems, in which it is necessary to find an optimal path around a newly introduced barrier and to take a shorter path through a hole opened up in a preexisting barrier, respectively. We argue that the ability to solve such problems qualifies the proposed hippocampal object as a cognitive map. Graph theory thus provides a sort of existence proof demonstrating that the hippocampus contains the necessary information to function as a map, in the sense postulated by others (O'Keefe, J., and L. Nadel. 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford, UK). It is also possible that the cognitive mapping functions of the hippocampus are carried out by parallel graph searching algorithms implemented as neural processes. This possibility has the great attraction that the hippocampus could then operate in much the same way to find paths in general problem space; it would only be necessary for pyramidal cells to exhibit a strong nonpositional firing correlate.
The phenomenon of animal navigation has thus far not been completely explained in physiological terms, although it now appears to be well established that several species utilize celestial aids in their navigation. The remarkably successful development in recent years of self-contained Inertial Navigation Systems for automatic indication of position and for the control of motion of man-made vehicles (missiles, airplanes, submarines) suggests the necessity of a reconsideration of some aspects of the problem of animal navigation in the light of these developments. The basic principle of inertial navigation is that of determination of direction, and of distance travelled, by means of a double integration with respect to time of acceleration, due regard being made for the fact that the motion is carried out with respect to a spherical, rotating earth. Certain inertial systems of a hybrid type utilize celestial navigation as a supplementary aid; for this purpose automatic star-tracking devices are employed.
Path integration (dead reckoning) is a computational process by which an animal can keep track of its position relative to some starting point by relying on self-generated information collected en route. The purpose of this paper is two-fold: first, to review four important models of path integration, analysing how the different models have evolved as a result of the authors’ particular focus; second, to assess what they have brought to the understanding of path integration. The more specific the model, the less it will be possible to apply it to different situations; the more general its nature, the less adequately it will represent the details of the behaviour to be modelled. In this context, the paper discusses how the authors envisioned the role of homing errors. The usefulness and limits of the different perspectives is discussed, in particular how well the models fit with observations. Finally, ways of improving and developing the modelling process are proposed.
Experimental lesion studies in monkeys have demonstrated that the cortical areas surrounding the hippocampus, including the entorhinal, perirhinal and parahippocampal cortices play an important role in declarative memory (i.e. memory for facts and events). A series of neuroanatomical studies, motivated in part by the lesion studies, have shown that the macaque monkey entorhinal, perirhinal and parahippocampal cortices are polymodal association areas that each receive distinctive complements of cortical inputs. These areas also have extensive interconnections with other brain areas implicated in non-declarative forms of memory including the amygdala and striatum. This pattern of connections is consistent with the idea that the entorhinal, perirhinal and parahippocampal cortices may participate in a larger network of structures that integrates information across memory systems.
The purpose of this paper is to demonstrate that rats can rapidly learn to locate an object that they can never see, hear, or smell provided it remains in a fixed spatial location relative to distal room cues. Four groups of rats were permitted to escape from opaque water onto a platform which was either just above or just below the water surface, and in either a fixed or varied location. Learning occurred rapidly except for the group for whom the escape platform was below the water surface and moved about from place to place. Transfer tests revealed that a spatial location search strategy was employed by the group for whom the platform was below water but in a fixed location. A second experiment investigated this learning further, revealing instantaneous transfer when the rats were required to approach the platform from a novel starting position. The data of both studies are discussed in relation to recent work on spatial memory in the rat. The concept of the “acuity” of spatial memory is introduced and the procedures used may provide a new approach to comparing spatial memory with classical and instrumental conditioning.
Unlike normal rats, rats with bilateral lesions in either the hippocampus or medial frontal cortex did not learn to swim from different directions to a hidden platform located at a specific place in a room. Experimental and clinical evidence indicates that a fronto-hippocampal system may provide an integrated neurological basis for spatial representational ability.
White and McDonald (1993, Behav Brain Res 55:269-281) previously reported that animals with amygdala lesions failed to acquire a conditioned-cue preference (CCP) based on spatial cues, but that animals with fornix lesions exhibited larger CCPs of this type than normal animals. The present experiments focused on the hippocampal interference with amygdala-based CCP learning inferred from this finding. In experiment 1 we tested the hypothesis that this interference was due to the acquisition of information about the maze and its environment during a 10 min period of free exploration of the maze before the start of CCP training, hitherto given to all animals in these experiments. Normal animals that were not preexposed to the maze and animals that were preexposed to a similar maze in a different room both exhibited larger CCPs than animals that were preexposed to the same maze in the same room as CCP training and testing. This suggests that normal animals acquire context-specific information during the preexposure period and that this may be the cause of the hippocampus-based interference with the amygdala-mediated CCP. In experiment 2 we attempted to determine if the information thought to be acquired by the hippocampal memory system interferes with acquisition or expression of the CCP. As previously demonstrated, animals that received fornix lesions before preexposure (i.e., before the start of the experiment) exhibited larger than normal CCPs. Animals that received fornix lesions after preexposure but before CCP training and animals that received fornix lesions after CCP training but before testing both exhibited normal CCPs.(ABSTRACT TRUNCATED AT 250 WORDS)
The idea that the hippocampus is essential for acquisition and retention of a transwitching (configural) problem is evaluated with a visual-tactile task. The task requires the rats to pull up a string of one of two sizes for food, as signalled by room lighting conditions. Rats received cathodal fimbria-fornix lesions either prior to or after learning the task. Rats with fimbria-fornix lesions were unimpaired in acquisition or retention. The results do not support the position that the hippocampal formation is essential for the acquisition and retention of a transwitching configural problem. The result is discussed in relation to the configural theory of hippocampal function.
A patient is reported in whom a classic amnesic syndrome developed as a result of repeated episodes of cerebral ischaemia, accompanied by seizures. The amnesia was very severe for both old and newly acquired memories and the critical lesions defined by MRI were circumscribed areas confined to CA1 and CA2 fields of both hippocampi.
We assessed the effects of hippocampal-formation (HF) damage on the rat's ability to learn two sets of concurrent visual discriminations. Each set included three problems. One set, called the transverse-patterning problem, was constructed so that each choice stimulus was ambiguous; sometimes it was the correct (+) and sometimes it was the incorrect (-) choice as follows: A+ vs. B-, B+ vs. C-, and C+ vs. A-. It could not be solved unless rats used configural associations. The stimuli were not ambiguous in the second, elemental problem set, A+ vs. B-, C+ vs. D-, and E+ vs. F-. Rats could solve this set without the use of configural associations. Rats with HF damage solved the set of elemental problems, but their performance on the transverse-patterning problem was impaired. These results support Sutherland and Rudy's (1989) theory that the hippocampal formation is critical for the acquisition of configural associations.
New Zealand male rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink conditioning paradigm using a 250-ms tone conditioned stimulus, a 100-ms airpuff unconditioned stimulus, and a 500-ms trace interval. Rabbits received bilateral hippocampal aspirations either 1 day or 1 month after learning. Controls consisted of time-matched sham-operated and neocortical aspirated rabbits. When retested on the trace paradigm, rabbits with hippocampal aspirations 1 day after learning were significantly and substantially impaired in the retention of trace conditioned responses. In contrast, rabbits that received hippocampal aspirations 1 month after training retained trace conditioned responses at a level comparable to that of the controls. Moreover, hippocampectomy had no effect on the retention of delay eyeblink conditioning. Thus, the hippocampus appears to be necessary for the retention of recently acquired, but not remotely acquired, trace conditioned responses.
The effects of cytotoxic lesions in either the anterior thalamic nuclei or the mamillary bodies were compared with those of fornix lesions on a test of spatial working memory. All three lesions impaired acquisition of a forced alternation task in a T-maze, but the disruptive effects of the mamillary body lesions were significantly less than those following either fornix or anterior thalamic damage. When the alternation task was changed, so as to increase proactive interference, the impairment associated with mamillary body damage became more evident and was now equal in severity to that in the animals with anterior thalamic lesions. The fornix lesion group were the most impaired. In contrast, all three groups performed normally on a test of object recognition. The results add weight to the view that hippocampal--anterior thalamic connections are critical for normal spatial memory and that the relative contribution of the mamillary bodies is task dependent.
During hoarding excursions, golden hamsters use distal landmarks and dead reckoning (updated signals derived from locomotion) to find their way back from a food source at the centre of a circular arena to their nest at the periphery. The preference for particular landmarks was assessed by setting landmark panoramas in conflict with dead reckoning. The hamsters tended to prefer horizontal landmarks to vertical ones when these landmarks were presented alone. However, in combination with a continuous background pattern including a single apex, vertical landmarks were more effective than horizontal ones. A panorama consisting of a vertical cylinder or bar and the background pattern was optimal provided the vertical landmark was aligned or superimposed on the apex of the background. The impact of a landmark panorama therefore depends on its particular components as well as on their mutual relationship.
There is controversy regarding the effect of isolated fornix damage on human memory. We report a patient who suffered a traumatic penetrating head injury that resulted in a significant and persistent anterograde amnesia. CT revealed a lesion that involved the region of the proximal, posterior portion of both fornices without evidence of damage to other hippocampal pathways or to other structures known to be critical for memory, such as the hippocampus, thalamus, or basal forebrain. The unique location of the lesion in this patient provides evidence supporting the role of isolated fornix lesions in amnesia.
Research on the neurobiology of learning and memory has been guided by two major theories: (i) memory as a psychological process and (ii) memory as a change in synaptic neural connectivity. It is not widely recognised that not only are these theories different but, moreover, they are fundamentally incompatible. Confusion concerning basic concepts in the learning and memory field in mammals has lead to the creation of an extensive but often inconclusive experimental literature. However, one important conclusion suggested by recent work in this field is that experience-dependent changes in neural connectivity occur in many different brain systems. Particular brain structures, such as the hippocampus, do not play any uniquely important role in experience-dependent behavior. Research in learning and memory can be best pursued on the basis of biological studies of animal behavior and a cellular approach to brain function.
Rats with damage to the hippocampal formation and allied structures are hyperactive in many test situations but the cause of this hyperactivity is not known. Here the activity of control rats and rats with fimbria-fornix lesions is documented in tests of overnight activity. Details of activity are then characterized from video recordings of behavior in an open field. Rats with fimbria-fornix lesions make significantly more stops of shorter duration and thus more individual trips than control rats but they do not differ in the distance traveled on individual trips or in travel speed. It is suggested that the main difference between fimbria-fornix rats and control rats is that when fimbria-fornix rats stop they remain "still" for shorter durations than do control rats. This finding is discussed in relation to a theory of locomotor/exploratory behavior, and in relation to its implications with respect to the performance of fimbria-fornix rats in studies of learning and memory.
The hippocampus is critical to declarative memory in humans. This kind of memory involves associations among items or events that can be accessed flexibly to guide memory expression in various and even new situations. In animals, there has been controversy about whether the hippocampus is specialized for spatial memory or whether it mediates a general memory function, as it does in humans. To address this issue we trained normal rats and rats with hippocampal damage on non-spatial stimulus-stimulus associations, then probed the nature of their memory representations. We report here that normal rats demonstrated two forms of flexible memory expression, transitivity, the ability to judge inferentially across stimulus pairs that share a common element, and symmetry, the ability to associate paired elements presented in the reverse of training order. Rats with neurotoxic damage limited to the hippocampus demonstrated neither form of flexible expression, indicating that non-spatial declarative processing depends specifically on the hippocampus in animals as it does in humans.
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.
During locomotion, mammals update their position with respect to a fixed point of reference, such as their point of departure, by processing inertial cues, proprioceptive feedback and stored motor commands generated during locomotion. This so-called path integration system (dead reckoning) allows the animal to return to its home, or to a familiar feeding place, even when external cues are absent or novel. However, without the use of external cues, the path integration process leads to rapid accumulation of errors involving both the direction and distance of the goal.
Therefore, even nocturnal species such as hamsters and mice rely more on previously learned visual references than on the path integration system when the two types of information are in conflict. Recent studies investigate the extent to which path integration and familiar visual cues cooperate to optimize the navigational performance.
1. Recent conceptualizations of the neural systems used during navigation have classified two types of sensory information used by animals: landmark cues and internally based (idiothetic; e.g., vestibular, kinesthetic) sensory cues. Previous studies have identified neurons in the postsubiculum and the anterior thalamic nuclei that discharge as a function of the animal's head direction in the horizontal plane. The present study was designed to determine how animals use head direction (HD) cells for spatial orientation and the types of sensory cues involved. 2. HD cell activity was monitored in the postsubiculum and anterior thalamic nucleus of rats in a dual-chamber apparatus in an experiment that consisted of two phases. In the first phase, HD cell activity was monitored as an animal moved from a familiar environment to a novel environment. It was hypothesized that if HD cells were capable of using idiothetic sensory information, then the direction of maximal discharge should remain relatively unchanged as the animal moved into an environment where it was unfamiliar with the landmark cues. In the second phase, HD cells were monitored under conditions in which a conflict situation was introduced between the established landmark cues and the animal's internally generated sensory cues. 3. HD cells were initially recorded in a cylinder containing a single orientation cue (familiar environment). A door was then opened, and the rat entered a U-shaped passageway leading to a rectangular chamber containing a different prominent cue (novel environment). For most HD cells, the preferred direction remained relatively constant between the cylinder and passageway/rectangle, although many cells showed a small (6-30 degrees) shift in their preferred direction in the novel environment. This directional shift was maintained across different episodes in the passageway/rectangle. 4. Before the next session, the orientation cue in the cylinder was rotated 90 degrees, and the animal returned to the cylinder. The cell's preferred direction usually shifted between 45 and 90 degrees in the same direction. 5. The rat was then permitted to walk back through the passageway into the now-familiar rectangle. Immediately upon entering the passageway, the preferred direction returned to its original (prerotation) orientation and remained at this value while the rat was in the rectangle. When the rat was allowed to walk back into the cylinder, one of three outcomes occurred: 1) the cell's preferred direction shifted, such that it remained linked to the cylinder's rotated cue card; 2) the cell's preferred direction remained unchanged from its orientation in the rectangle; or 3) the cell's preferred direction shifted to a new value that lay between the preferred directions for the rotated cylinder condition and rectangle. 6. There was little change in the HD cell's background firing rate, peak firing rate, or directional firing range for both the novel and cue-conflict situations. 7. Simultaneous recordings from multiple cells in different sessions showed that the preferred directions remained "in register" with one another. Thus, when one HD cell shifted its preferred direction a specific amount, the other HD cell also shifted its preferred direction the same amount. 8. Results across different series within the same animal showed that the amount the preferred direction shifted in the first Novel series was about the same amount as the shifts observed in subsequent Novel series. In contrast, as the animal experienced more Conflict series, HD cells tended to use the cylinder's cue card less as an orientation cue when the animal returned to the rotated cylinder condition from the rectangle. 9. These results suggest that HD cells in the postsubiculum and anterior thalamic nuclei receive information from both landmark and idiothetic sensory cues, and when both types of cues are available, HD cells preferentially use the landmark cues as long as they are perceived
Spontaneous alternation has been studied in laboratory tests given to rodents since 1935. Herein is described a simple new technique that allows the animal to perform without intertrial handling. The apparatus has a centered covered 'home base' and two relatively exposed arms. When presented with large food pellets, the rats carry them from the exposed arms to the home base before consuming them. The utility of the method is demonstrated in four exemplar paradigms ranging from two choice tasks to food 'hoarding' and exploratory tasks. The procedure can be modified for forced and other alternation paradigms and allows collection of a variety of psychophysical measures. The strength of the task is that it provides an analogue of natural foraging behavior.
Damage to either the fimbria-fornix or to the hippocampus can produce a deficit in spatial behavior and change in locomotor activity but the extent to which the two kinds of damage are comparable is not known. Here we contrasted the effects of cathodal sections of the fimbria-fornix with ibotenic acid lesions of the cells of the hippocampus (Ammon's horn and the dentate gyrus) on place learning in a swimming pool and on circadian activity. Rats in both ablation groups were impaired relative to control rats in learning a single place response but they did acquire the response as measured by swim latencies, errors, and by enhanced searching on probe trials. They were also more active than the control group on the test of activity. Nevertheless, the fimbria-fornix group was initially more impaired on learning and was more active than the hippocampal group. Analysis of the strategies used in learning indicated that the lesion groups were very similar to each other but different from the control group especially in that at asymptotic performance, rats in both lesion groups made rather tight loops as they swam toward the platform. This strategy likely contributed to the greater proportion of time they spent swimming in the correct quadrant on the subsequent probe trial. These findings confirm that rats with fimbria-fornix or hippocampal damage display impairments in place learning and are hyperactive but also show that there are lesion differences. The results are discussed with respect to the relative effectiveness of the lesions and the possibility that fibers in the fimbria-fornix may mediate some functions that are not attributable to the hippocampus.
Normal rats rapidly acquire and remember associations between nonspatial stimuli as expressed in the social transmission of food preferences. In the present study, rats with selective neurotoxic lesions including all subdivisions of the hippocampal region (hippocampus proper, dentate gyrus, and subiculum) normally acquired and briefly retained the food odor association as demonstrated by intact memory immediately after social training. However, long-term memory in these animals was severely impaired in contrast to strong 24-h retention by intact rats. More selective lesions to the hippocampus proper plus dentate gyrus alone, or the subiculum alone had no effect on memory at either test interval. These findings indicate that the hippocampal region is required for long-term retention of a nonspatial form of natural memory.
The strong signal carried by head direction cells in the postsubiculum complements the positional signal carried by hippocampal place cells; together, the directional and positional signals provide the information necessary to permit rats to generate and carry out intelligent, efficient solutions to spatial problems. Our opinion is that the hippocampal positional system acts as a cognitive map and that the role of the directional system is to put the map into register with the environment. In this way, paths found using the map can be properly executed. Head direction cells have recently been discovered in parts of the thalamus reciprocally connected with the postsubiculum; such cells provide important clues to the organization of the directional system.
Substantial information is available concerning the influence of global hippocampal lesions on spatial learning and memory, however the contributions of discrete subregions within the hippocampus to these functions is less well understood. The present investigation utilized kainic acid to bilaterally lesion specific areas of the rat hippocampus. These animals were subsequently tested on a spatial orientation task using a circular water maze, and on an associative/contextual task using passive avoidance conditioning. The results indicate that both the dorsal CA1 and the ventral CA3 subregions play important roles in learning. Specifically, CA1 lesions produced a deficit in the acquisition of the water maze task and a significant memory impairment on the passive avoidance task. CA3 lesions also caused learning deficits in the acquisition of the water maze task, and produced even greater impairments in performance on the passive avoidance task. We conclude that CA1 and CA3 hippocampal subregions each play significant roles in the overall integration of information concerning spatial and associative learning.
Much of the evidence used to implicate the hippocampus in learning and memory has been obtained from clinical cases and/or experimental studies with animals where the damage is extensive and includes more than just the hippocampus. When the damage is limited to the cells that comprise the hippocampus (CA1-CA3 pyramidal cells, hilar and granule cells in the dentate gyrus) the effect on behavior in the rat is more limited than what is usually reported. Selective, axon-sparing ibotenic acid lesions of the hippocampus were used in the experiments that are reviewed to study the effects of removing the hippocampus on: (1) the acquisition of spatial and non-spatial information; (2) complex, non-spatial representational learning; and (3) acquisition and utilization of contextual information. The results indicated that rats with the hippocampus removed were impaired on those tasks that require the utilization of spatial and contextual information but performed like controls in learning about and handling (even complex) non-spatial information. Future research utilizing selective lesions of the hippocampus and sensitive behavioral testing techniques should help clarify the extent to which the impairments in the acquisition of spatial information and the ability to utilize contextual, background cues can be reduced to a single, underlying learning process.