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New views on old memories: Re-evaluating the role of the hippocampal complex
Abstract
Evidence of temporally graded retrograde amnesia (RA) following hippocampal damage has fuelled the long-standing belief that memory undergoes a consolidation process, whereby memories are progressively modified in neocortical regions until they are independent of the hippocampal (HPC) complex. Support for this position derives from both the animal and human RA literature, although the results are not consistent. Specifically, consolidation theory does not account for loss of episodic (detail) information in humans and context-dependent information in animals, which often extend back for much of the life span. We discuss an alternative approach, the Multiple Trace Theory, which suggests that the HPC complex contributes to the retrieval of recent and remote episodic and context-dependent memories. According to this view, such memory traces are represented as spatially distributed interactions between the HPC and neocortex that persist for as long as those memories exist. On the other hand, semantic, or context-free, memories can become independent of the HPC as consolidation theory predicts. In support of this view, we report recent accounts of relatively flat RA gradients in autobiographical and spatial detail loss in patients and animal models with extensive bilateral HPC lesions. By comparison, temporally graded RA was observed in tests of semantic and context-free memory. We also report neuroimaging studies in which hippocampal activity, elicited during recollection of autobiographical memories, did not distinguish recent from remote episodes. Our discussion suggests ways to reconcile discrepancies in the literature and guide predictions of the occurrence of flat versus temporally limited gradients of remote episodic and semantic memory loss following lesions to HPC.
... In contrast, memory representations learned in the Hebb paradigm are by definition learned from repetition. It has been suggested that repetition of the same memory content in different contexts results in a context-free (i.e., non-episodic) semantic memory representation (Baddeley, 1988;Moscovitch et al., 2005;Rosenbaum et al., 2001). Hence, it is possible that age-related deficits are present for memories of single experiences but not for representations learned from repetition, regardless of whether these memories are dependent on pairwise association learning or not. ...
... It could be that age-related memory deficits are specific to associative representations of single experiences, that is, episodic memories. It has been proposed that repeated exposure results in context-free semantic memories (e.g., Rosenbaum et al., 2001). If that is the case, then older adults should be as good as younger adults in learning context-free semantic memories for pairwise associations. ...
... This suggests that older adults are at a disadvantage when the task forces participants to rely on strengthening pairwise associations over repetitions. Consequently, the absence of age differences in Experiment 1 cannot be explained by repetition learning directly resulting in context-free, non-episodic memory representations (i.e., Rosenbaum et al., 2001). Rather, the lists of consonants we used in Experiment 1 were learned through a mechanism other than the strengthening of pairwise associations, most likely a chunking mechanism (Burgess & Hitch, 2006;Page & Norris, 2009) that seems to be spared in old age. ...
Repetition learning has been frequently studied using the Hebb effect: Immediate serial recall performance improves for a memory list which is repeated amidst other, non-repeated lists. Previous research has suggested that older adults learn as well as younger adults in the Hebb paradigm. Because older adults show an age-related deficit in associative episodic memory, this suggests that learning in the Hebb paradigm is not driven by associative memory. In fact, it has been shown that learning sequentially presented lists through repetition is likely to be driven by a chunking mechanism, by which the whole list is integrated into a single unified representation. Here, we investigate age differences in the Hebb paradigm to determine the conditions under which repetition learning relies on associative episodic memory. We found that older adults learn at the same rate as younger adults in a standard Hebb paradigm with lists of letters. By contrast, Hebb repetition learning of pairwise associations of words was slower in older than in younger adults. Our results suggest that (a) repetition learning is only driven by associative memory when learning pairwise associations is required to solve the task, and (b) that older adults’ capability to learn from repetition is as good as that of younger adults whenever memory lists are presented in sequence. Thus, the process of chunk formation is largely preserved in old age, at least in the verbal domain.
... Multiple trace theory (MTT), an alternative to the standard model of SC, accounts for these findings arguing that irrespective of when they are acquired, vivid autobiographical memories always engage the HPC (Nadel and Moscovitch 1997;Nadel et al. 2000;Rosenbaum et al. 2001;Gilboa et al. 2004;Meeter and Murre 2004;Moscovitch et al. 2005;Rekkas and Constable 2005). Here, remote memories retain rich contextual detail (Suzuki and Naya 2011) as long as the trace in the HPC is dominant at the time of retrieval. ...
... Behaviorally, we saw no effect of inhibiting the dCA1 with CNO on recall at 1 d and unexpectedly there was an increase in freezing at 21 d. The incubation of fear hypothesis originally proposed by Eysenck (1968) states that repeated exposure to an unreinforced conditioned stimulus (i.e., the training context) following acquisition of a classical aversive conditioned response (i.e., freezing) provided that the conditioned stimulus (i.e., the shock) is a strong stimulus, will serve to enhance the conditioned response over time (Richards and Martin 1990). In previous rodent studies, which have examined fear memory recall across recent and remote time points, fear responses related to the training context tended to either stay stable (Wiltgen and Silva 2007;Poulos et al. 2016) or strengthen over time (Houston et al. 1999;Balogh et al. 2002;Frankland et al. 2004;Poulos et al. 2016) supporting Eysenck's hypothesis. ...
... In previous rodent studies, which have examined fear memory recall across recent and remote time points, fear responses related to the training context tended to either stay stable (Wiltgen and Silva 2007;Poulos et al. 2016) or strengthen over time (Houston et al. 1999;Balogh et al. 2002;Frankland et al. 2004;Poulos et al. 2016) supporting Eysenck's hypothesis. However, there have also been human studies where this effect was not observed (Richards and Martin 1990), and in the current study, we saw a decline in freezing over time. While we did not test fear generalization, it is possible that this decline in the conditioned response was accompanied by an increase in generalization (Wiltgen and Silva 2007). ...
Systems consolidation (SC) theory proposes that recent, contextually rich memories are stored in the hippocampus (HPC). As these memories become remote, they are believed to rely more heavily on cortical structures within the prefrontal cortex (PFC), where they lose much of their contextual detail and become schematized. Odor is a particularly evocative cue for intense remote memory recall and despite these memories being remote, they are highly contextual. In instances such as posttraumatic stress disorder (PTSD), intense remote memory recall can occur years after trauma, which seemingly contradicts SC. We hypothesized that odor may shift the organization of salient or fearful memories such that when paired with an odor at the time of encoding, they are delayed in the de-contextualization process that occurs across time, and retrieval may still rely on the HPC, where memories are imbued with contextually rich information, even at remote time points. We investigated this by tagging odor- and non-odor-associated fear memories in male c57BL/6 mice and assessed recall and c-Fos expression in the dorsal CA1 (dCA1) and prelimbic cortex (PL) 1 or 21 d later. In support of SC, our data showed that recent memories were more dCA1-dependent whereas remote memories were more PL-dependent. However, we also found that odor influenced this temporal dynamic, biasing the memory system from the PL to the dCA1 when odor cues were present. Behaviorally, inhibiting the dCA1 with activity-dependent DREADDs had no effect on recall at 1 d and unexpectedly caused an increase in freezing at 21 d. Together, these findings demonstrate that odor can shift the organization of fear memories at the systems level.
... The transsylvian approach, as described by Yaşargil, is performed by splitting the sylvian fissure, followed by a corticectomy on the polar planum of the superior temporal gyrus at the level of the limen insula. 35,[38][39][40][41][42] Disturbances of the visual field, 6,10,13,37,52,53 memory, [54][55][56][57][58] and language 7,59-62 are the most common neurological deficits after surgical exploration of the temporal horn. Variations on the classical approaches have been proposed based on anatomic considerations, 3,4,8,11,12,14,25,26,28,29 and to avoid brain retraction. ...
... While intracerebral lesions or proposed surgical treatments affect white matter arrangements, surgeons must keep in mind that interrupting the fiber tracts might cause more severe and permanent neurological deficits than cortical damage does. 60,61 Despite increasing understanding of the fiber tract functions within the temporal and limbic lobes concerning memory [54][55][56][57][58] and language, the proposed variations on surgical approaches 3,4,8,9,11,12,14,20,25,26,28,30,44,50,51 and their related anatomic studies 2,3,5,7,26,36,67-71 concentrate mostly on the fiber topography of the optic radiation and how to prevent postoperative defects in the optical field. But the literature has underestimated the damage to the superior longitudinal fasciculus, occipitofrontal fasciculus, uncinate fasciculus, anterior commissure, temporopontine, and inferior and posterior thalamic peduncle fibers on the lateral surface, as well as the inferior longitudinal fasciculus, cingulum, and fimbria fibers on the inferior surface. ...
... 61 Interruption of the uncinate fasciculus relates to disturbances of episodic context (personal experience) and semantic context (knowledge of concepts and facts). 56 Functional disturbances that are caused by lesions restricted to the anterior commissure have not been reported; however, patients harboring callosal agenesis supposedly compensate for interhemispheric visual, auditory, and somatosensory information transfers partially through the anterior commissure. 72 Disturbances strictly related to temporopontine fiber interruptions have not been reported, but, as a component of the temporoparieto-occipitopontine fibers, they are supposedly associated with an oculocephalic response to visual stimuli. ...
BACKGROUND: Surgical access to the temporal horn is necessary to treat tumors and vascular lesions, but is used mainly in patients with mediobasal temporal epilepsy. The surgical approaches to this cavity fall into 3 primary categories: lateral, inferior, and transsylvian. The current neurosurgical literature has underestimated the interruption of involved fiber bundles and the correlated clinical manifestations.
OBJECTIVE: To delineate the interruption of fiber bundles during the different approaches to the temporal horn.
METHODS: We simulated the lateral (trans-middle temporal gyrus), inferior (transparahippocampal gyrus), and transsylvian approaches in 20 previously frozen, formalin-fixed human brains (40 hemispheres). Fiber dissection was then done along the lateral and inferior aspects under the operating microscope. Each stage of dissection and its respective fiber tract interruption were defined.
RESULTS: The lateral (trans-middle temporal gyrus) approach interrupted “U” fibers, the superior longitudinal fasciculus (inferior arm), occipitofrontal fasciculus (ventral segment), uncinate fasciculus (dorsolateral segment), anterior commissure (posterior segment), temporopontine, inferior thalamic peduncle (posterior fibers), posterior thalamic peduncle (anterior portion), and tapetum fibers. The inferior (transparahippocampal gyrus) approach interrupted “U” fibers, the cingulum (inferior arm), and fimbria, and transected the hippocampal formation. The transsylvian approach interrupted “U” fibers (anterobasal region of the extreme capsule), the uncinate fasciculus (ventromedial segment), and anterior commissure (anterior segment), and transected the anterosuperior aspect of the amygdala.
CONCLUSION: White matter dissection improves our knowledge of the complex anatomy surrounding the temporal horn. Identifying the fiber bundles at risk during each surgical approach adds important information for choosing the appropriate surgical strategy.
... Other studies that have used a similar approach have similarly reported a loss of detail from all periods (Kitchener et al., 1998;Cipolotti et al., 2001;Westmacott et al., 2001;Rosenbaum et al., 2001Rosenbaum et al., , 2004. Subjects with hippocampal damage recall an equivalent (small) amount of detail about autobiographical memories from all time periods, whilst control subjects produce progressively fewer details as memories age Rosenbaum et al., 2004). ...
... However, also like episodic memory, recent evidence suggests that the spatial memory measured on standard tests may be abnormal. A recent extensive study of a severely amnesic patient reported good memory for general layout and major landmarks of the neighbourhood lived in since a child, but impairments at remembering details of landmarks and less salient features Rosenbaum et al., 2001). Thus after hippocampal damage, spatial memories might also be deficient in detail and complexity at all time periods. ...
... Additionally, the nature of the exposure that humans and non-human animals have to spatial information differs, if, for example, the recall of neighbourhoods in humans is compared with an animal's memory for platform position in a water-maze. Rosenbaum et al. (2001) found that rats that were trained pre-operatively on a maze task that encouraged the formation of multiple representations were less impaired after hippocampal lesions than those trained on an invariant version (though they performed worse than controls which performed similarly after both types of training). ...
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.
... However, this does not indicate a function. For some time it has been suggested that the hippocampus is involved in learning and memory (Wagner, 2001;Rosenbaum, et al., 2001;Nestor, et al., 2002), this belief is based on human surgical evidence, where removal / deafferentation of all or parts of the hippocampus produces impaired learning/memory (Moscovitch and McAndrews, 2002). This property is thought to be linked to the ability of the neurons, in the hippocampus, to alter their responses to a stimulus or series of stimuli, reinforcing that stimulus the next time it is received -this property is referred to as long-term potentiation (Nakic, et al., 1998;Derrick, et al., 2000). ...
... One of the problems of quantitative analysis in the brain is the sheer number of cells present in each structure. Actual cell counts are impossible, as estimates of the number of granule cells in a 30 day old male Wister rat hippocampus range &om 890 thousand to 1.2 million cells (West, et al, 1991), another study estimates there to be approximately 15 million granule cells in the human hippocampus (Rosenbaum, et al., 2001). All these estimates were obtained using stereological techniques or 'probes'; the cell counts obtained using two different probes in the hippocampus of rats in both cases of the same age, sex and strain clearly demonstrate that cell counting is highly variable (West, et al., 1991). ...
p>The aim of this thesis is to investigate the control of dentate neurogenesis, especially after seizure, and to identify the principle cells involved in these processes. I have used a combination of in vivo and in vitro techniques to investigate the mechanisms and control of seizure induced denatate neurogenesis, chemoconvulsant kainate was used to induce seizures in all seizure models, maximizing the potential for comparison between experiments.
Initial in vitro work established conditions in which cell death and proliferation could be accurately and reproducibly quantified in organotypic hippocampal slice cultures. Subsequent experiments established that in immature tissue kainate induced cell death, followed by increased neurogenesis.
In vivo experiments in adult rats using a ‘clonal; BrdU labelling technique, where a cohort of cells labelled prior to seizure induction were followed in recovery, found that the prelabelled cohort contributed less to seizure induced cell proliferation than the cohort of cells that were not dividing prior to seizures implying the recruitment of an additional dividing cell population by seizures.
Astrocytes with radial glial like morphology are putative stem cells for dentate neurogenesis. To test our recruitment hypothesis, I used transgenic mice expressing enhanced green fluorescent protein under the hGFAP promoter to readily identify a subset of the radial glial like cells, and found their proliferation was selectively increased (10 fold vs. 2.5 fold overall increase in proliferation) in response to seizures.
The data obtained suggest that seizures result in either death or inactivation of a progenitor cell population with a consequent recruitment of either quiescent or slowly dividing stem cells, which divide to replenish the progenitor cell population and restore neurogenesis. This work also identifies GFAP expressing cells with a radial glial morphology as a quiescent stem cell population selectively recruited to divide by brain injury due to seizures, and is the first report of recruitment of an identified stem cell population in the dentate after brain injury.</p
... En accord avec cette théorie, des rats placés en permanence dans un environnement complexe et riche en stimuli (multiples voies d'accès à la nourriture/eau, sur deux étages, présence de congénères, etc.) appelé « le village », ne sont pas perturbés pour retrouver la nourriture suite à une lésion de l'HPC (Winocur et al., 2005a). Ces résultats suggèrent l'établissement d'une carte cognitive corticale de l'environnement spatial liée à la familiarité de l'environnement spatial, permettant alors un maintien de certaines informations indépendamment de l'HPC (Rosenbaum et al., 2000(Rosenbaum et al., , 2001Tse et al., 2011). ...
... Ainsi, en accord avec la prédiction du modèle standard de la consolidation, la mémoire sémantique ne dépendrait de l'HPC que le temps de l'intégration de ces aspects sémantiques au réseau préexistant, période après laquelle le réseau serait dépendant uniquement des aires corticales. Plusieurs études ont été menées chez l'animal (Kim and Fanselow, 1992;Mumby and Glenn, 2000;Winocur et al., 2005b;Zola-Morgan and Squire, 1990) et chez l'Homme (Cipolotti et al., 2001;Viskontas et al., 2000) permettant d'appuyer ce modèle (pour revue, voir Nadel et al., 2007;Rosenbaum et al., 2001). Bien que la plupart des résultats concernant la mémoire sémantique vont dans le sens d'un désengagement graduel de l'HPC, ~ 30 ~ certaines études mettent en évidence des résultats contradictoires . ...
Initialement encodés dans l’hippocampe, les nouveaux souvenirs déclaratifs, aussi appelés engrammes, deviennent progressivement dépendants d’un réseau distribué de neurones corticaux au cours de leur maturation. Bien que le rôle du cortex dans le stockage de la mémoire ancienne (MA) ait été clairement démontré, plusieurs études montrent que certains réseaux corticaux pourraient être recrutés précocement, dès l’encodage, et participeraient après maturation, au stockage de la trace mnésique. Ceci a notamment été suggéré pour le cortex frontal, dans lequel des changements structuraux et fonctionnels précoces ont été observés, indiquant que la maturation de la trace corticale nécessiterait des renforcements dans la connectivité fonctionnelle entre les différentes structures dépositaires de la trace mnésique. Grâce au marqueur d’activité neuronale c-fos, nous avons étudié l’évolution temporelle, au cours de la consolidation mnésique, de la connectivité fonctionnelle des régions frontales : le Cortex PréFrontal médian (CPFm), les parties antérieure (CCa) et postérieure (CCp) du Cortex Cingulaire et le Cortex OrbitoFrontal (COF), lesquelles pourraient participer à la maturation de l’engramme. Nous avons comparé l’activité dans ces régions lors du rappel d’une mémoire olfactive associative récente (MR) ou ancienne à l’aide d’une tâche de transmission sociale de préférence alimentaire.Nous avons identifié trois régions corticales clés co-activées lors du rappel de la MA, suggérant qu’elles forment un nœud critique au sein d’un réseau cortical plus vaste, nécessaire à la formation de l’engramme. L’analyse des corrélations interrégionales des activités neuronales révèle que l’activité du CPFm et du COF est corrélée dès le rappel de la MR, bien que leur recrutement soit dépendant de l’âge de la mémoire. Cette connectivité fonctionnelle s’appuie sur une connectivité anatomique unidirectionnelle entre le CPFm et le COF. Par contraste, le CCp est activé uniquement lors du rappel d’une mémoire récente. Par une approche pharmacogénétique, nous avons sélectivement inhibé le CPFm et révélé son implication lors de la phase d’encodage, mais également dans le rappel de la MR et de la MA. L’ensemble de ces résultats suggèrent que bien que le processus de maturation de la trace mnésique au niveau cortical soit spécifique à chaque région, il requiert une connectivité fonctionnelle entre plusieurs régions corticales dont les cinétiques d’activation distinctes mais coordonnées permettent le stockage et l’expression à long terme du souvenir.Des altérations focalisées de cette connectivité, notamment lors du vieillissement, pourraient ralentir le processus d’apprentissage et/ou changer les stratégies d’apprentissage mis en place par l’animal pour résoudre une tâche complexe. À l’aide un test de discrimination spatiale, au cours de huit sessions d’apprentissage dans un labyrinthe radiaire à huit bras sur une large cohorte de souris âgées (22 mois), nous avons pu isoler deux populations : l’une avec une vitesse d’apprentissage similaire à celle d’un groupe de souris jeunes, et l’autre avec une vitesse d’apprentissage réduite. Des expériences futures permettraient de déterminer dans quelle mesure la connectivité fonctionnelle cérébrale est altérée de manière différentielle dans ces deux populations de souris âgées.
... The idea, then, is to train rats in a maze for several weeks, and once a rat has mastered, and perhaps overlearned, navigation within the maze, the hippocampus is selectively disrupted with very precise chemical lesions. In this way, researchers create a model of retrograde amnesia that is immune to individual differences in lesion size and location that are often seen in amnesic patients (Rosenbaum, Winocur, and Moscovitch 2001;Frankland and Bontempi 2005). While we have discussed some of the caveats regarding differences in human versus rat spatial navigation (see chapter 4), there is no strong reason to think familiarity itself will differ strongly between the species. ...
... Fine, detailed information about an environment, in contrast, would continue to rely on hippocampal function, similar to detailed episodic representations, regardless of how long ago that information was acquired. An important addition to MTT is that the transformed memory is not believed to replace the initial, more detailed memory but rather the two representations can coexist and even interact when the situation requires it (Rosenbaum, Winocur, and Moscovitch 2001). ...
... Finally, it has been suggested that, over time, a process of semanticisation occurs whereby episodic ABMs are transformed into less detailed, schematic memories more akin to semantic representations [23]. By this view, recent memories are more likely to encompass sensory-perceptual elements [24], whereas remote ABMs represent an abstracted or semanticised gist of the formerly evocative event [25]. Accordingly, these remote ABM schematic accounts are posited to draw heavily upon regions specialised for semantic processing in the brain [4]. ...
... This finding is consistent with the proposal that old memories undergo a process of semanticisation [78]. Over time, repeated recollection and rehearsal of remote memories facilitates abstraction of the gist of the episode, divested of its accompanying sensory-perceptual details [25]. This process of abstraction therefore produces a largely schematic or overgeneral account of the formerly evocative event [4,7]. ...
The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events.
... Patterns of preserved and impaired aspects of remote spatial memory in hippocampal amnesia support the idea that the hippocampus is not needed for representing coarse or schematic spatial representations of large-scale environments that were formed long ago, similar to semantic memory. Conversely, fine-grained details of remotely learned environments continue to rely on hippocampal function, as in the case of episodic memory (Rosenbaum et al., 2001;Moscovitch et al., 2005). Separate but complementary evidence of slow semantic memory acquisition in developmental amnesia in the context of impaired episodic memory (Gardiner et al., 2008) offers support for the view that statistical regularities of multiple episodes or learning experiences can be extracted independent of the hippocampus (McClelland et al., 1995). ...
... We have reported comparable dissociations in adult humans and rats with hippocampal lesions who show extensive, ungraded loss of remote memory acquired long before lesion onset if the memory continues to rely on its initial, detailed context, but sparing of remote memory if the memory is transformed from a contextually dependent one to one that is more semantic or schematic (Rosenbaum et al., 2001;Moscovitch et al., 2005Moscovitch et al., , 2006Winocur et al., 2005Winocur et al., , 2010a. Here, we extend this distinction to show that new spatial learning is possible when it occurs over many years, but the representations are not sufficient to support the precise placement of multiple landmarks in relation to each other when they are located in close proximity, unlike findings in adult-onset amnesic cases. ...
The hippocampus is believed to have evolved to support allocentric spatial representations of environments as well as the details of personal episodes that occur within them, whereas other brain structures are believed to support complementary egocentric spatial representations. Studies of patients with adult-onset lesions lend support to these distinctions for newly encountered places but suggest that with time and/or experience, schematic aspects of environments can exist independent of the hippocampus. Less clear is the quality of spatial memories acquired in individuals with impaired episodic memory in the context of a hippocampal system that did not develop normally. Here we describe a detailed investigation of the integrity of spatial representations of environments navigated repeatedly over many years in the rare case of H.C., a person with congenital absence of the mammillary bodies and abnormal hippocampal and fornix development. H.C. and controls who had extensive experience navigating the residential and downtown areas known to H.C. were tested on mental navigation tasks that assess the identity, location, and spatial relations among landmarks, and the ability to represent routes. H.C. was able to represent distances and directions between familiar landmarks and provide accurate, though inefficient, route descriptions. However, difficulties producing detailed spatial features on maps and accurately ordering more than two landmarks that are in close proximity to one another along a route suggest a spatial representation that includes only coarse, schematic information that lacks coherence and that cannot be used flexibly. This pattern of performance is considered in the context of other areas of preservation and impairment exhibited by H.C. and suggests that the allocentric-egocentric dichotomy with respect to hippocampal and extended hippocampal system function may need to be reconsidered.
... Spatial memory, based on the ability to form and remember allocentric spatial relationships in a complex environment, is known to be particularly vulnerable to the effects of normal aging in animals and humans (Barnes, 1979;Light, 1983;Park et al., 1983;Gallagher and Pelleymounter, 1988;Moffat et al., 2006). The loss of spatial memory in old age is related to failures in recalling contextually bound episodic events and has been attributed to changes in the hippocampus, a brain region that is functionally linked to spatial information processing (O'Keefe and Nadel, 1978;Maguire et al., 1996, Rosenbaum et al., 2001 and one of the first structures to show significant deterioration as part of the aging process (Gallagher et al., 1995;Geinisman et al., 1995;Winocur and Gagnon, 1998). ...
... Once established, and with time and experience, the core information inherent in these representations is integrated with pre-existing knowledge to form less detailed semantic or schematic memories. The same process is thought to occur with respect to spatial memory (Rosenbaum et al., 2001;Moscovitch et al., 2005). In the present study, the young rats raised in the village had the opportunity to learn the locations of various reward objects in relation to specific contextual cues, as well as to form a more schematic representation of the entire environment that was less contextually bound. ...
The effect of aging on remote spatial memory was tested in a group of 2-year-old rats (VR-O) that, as young adults, were reared for 3 months in a complex 'village' environment. The VR-O rats exhibited significant savings in finding the locations of specific reward compartments within the village, relative to a group of old rats (VNR-O) experiencing the village for the first time. The VNR-O rats were also impaired, relative to naive young rats, in learning the reward locations. Probe tests indicated that the VR-O rats retained allocentric spatial memory for the environment and were not using sensory or other non-spatial cues to guide behaviour. Overall, the results indicate that the aged rats experienced a decline in the ability to learn and remember detailed spatial relationships and that the VR-O group's successful performance on the remote spatial memory test was guided by a form of schematic memory that captured the essential features of the village environment. The potential contribution of the hippocampus to the pattern of lost and spared learning and memory observed in the aged rats was discussed.
... One plausible explanation could be that the autistic participants in these studies were predominantly in the younger age range (<20 years old), consistent with our findings indicating a reduction in the functional connectivity of the hippocampal memory network with age in autistic individuals. Given the limited understanding of vTL-based functional connectivity in ASD, our study suggests that challenges in semantic processing (Ehlen et al., 2020;Foldager et al., 2023) may be associated with reduced connections of the vTL with other brain regions such as the dorsolateral prefrontal cortex, fronto-insular cortex, and hippocampus, which play crucial roles in information encoding and retention (Rosenbaum et al., 2001;O'Reilly and Norman, 2002;Postle, 2009;Dickerson and Eichenbaum, 2010), as well as with motor-sensory regions such as the fusiform gyrus and pre/postcentral gyri, involved in processing and representing multimodal information (Rogers et al., 2005;Pulvermuller et al., 2009;Binkofski and Buxbaum, 2013;Chen and Rogers, 2015;Lambon Ralph et al., 2016;Bi, 2021). ...
Introduction
Although memory challenges in autistic individuals have been characterized recently, the functional connectivity of the hippocampus and ventral temporal lobe, two structures important for episodic and semantic memory functions, are poorly understood in autistic individuals. Moreover, age-related differences in the functional connectivity associated with these two memory networks are unrevealed.
Methods
The current study investigated age-related differences in intrinsic connectivity of the hippocampal and ventral temporal lobe (vTL) memory networks in well-matched ASD (n = 73; age range: 10.23–55.40 years old) and Non-ASD groups (n = 74; age range: 10.46–56.20 years old) from the open dataset ABIDE-I. Both theory-driven ROI-to-ROI approach and exploratory seed-based whole-brain approach were used.
Results and discussion
Our findings revealed reduced connectivity in ASD compared to Non-ASD peers, as well as an age-related reduction in the connectivity of hippocampal and vTL networks with triple networks, namely, the default mode network (DMN), the central executive network (CEN), and the salience network (SN), potentially underpinning their challenges in memory, language, and social functions. However, we did not observe reliable differences in age-related effects between the ASD and Non-ASD groups. Our study underscores the importance of understanding memory network dysfunctions in ASD across the lifespan to inform educational and clinical practices.
... Taken together, the results speak to a fundamental distinction between remote memory episodic and semantic information. Whereas detailed memory for autobiographical episodes is dependent on the medial temporal lobes for as long as the memory exists, memory for semantic information, such as famous people, is dependent on the medial temporal lobes (hippocampus and entorhinal cortex) only until the information is consolidated elsewhere, a process than can take as long as a decade in humans (Haist et al., 2001;Rosenbaum, Winocur, & Moscovitch, 2001;Westmacott et al., 2001). ...
Memory for famous individuals was assessed by the use of a recognition test in which participants first made familiarity judgments, followed by forced-choice decisions to specific probes for identity. Patients with temporal lobe epilepsy (TLE) or excisions, 12 left hemisphere and 12 right hemisphere, and 18 control participants identified famous figures across 3 decades (1970s–1990s). Only patients with right TLE were impaired at familiarity judgments of faces; this deficit was evident only for the most recent decades. Both groups of patients, however, were impaired at naming famous faces and at providing semantic information about famous people. These findings suggest the integrity of temporal structures in both hemispheres is critical for retrieval of detailed semantic information about famous individuals.
... Using a Sternberg partial report task, Lu, Neuse, Madigan, and Dosher (2005) also found MCI participants' iconic memory to decay much faster than healthy controls, e.g., having less than one-fourth of memory duration of healthy controls. Since the medial temporal lobe, especially the hippocampus, plays a key role in supporting detailed spatial memory (e.g., Moscovitch, Nadel, Winocur, Gilboa, & Rosenbaum, 2006;Rosenbaum, Winocur, & Moscovitch, 2001), both our findings (i.e., on misbinding and location precision) suggest impairments in medial temporal lobe functioning in MCI. Indeed, volumetric studies of hippocampal structure on both participants with AD and MCI reported significant abnormalities (Van Der Flier et al., 2002), which further indicated that the structure changes might be crucial for the deficits and may happen even in early stages of cognitive impairment (Alsop, Casement, de Bazelaire, Fong, & Press, 2008;Massa et al., 2020;Rodriguez et al., 2000). ...
To better understand working memory (WM) deficits in Mild Cognitive Impairment (MCI), we examined information precision and associative binding in WM in 21 participants with MCI, compared to 16 healthy controls, using an item-location delayed reproduction task. WM, along with other executive functions (i.e. Trail Making Task (TMT) and Stroop task), were measured before and after a 2-h nap. The napping manipulation was intended as an exploratory element to this study exploring potential impacts of napping on executive functions.
Compared to healthy participants, participants with MCI exhibited inferior performance not only in identifying encoded WM items but also on item-location associative binding and location precision even when only one item was involved. We also found changes on TMT and Stroop tasks in MCI, reflecting inferior attention and inhibitory control. Post-napping performance improved in most of these WM and other executive measures, both in MCI and their healthy peers.
Our study shows that associative binding and WM precision can reliably differentiate MCIs from their healthy peers. Additionally, most measures showed no differential effect of group pre- and post-napping. These findings may contribute to better understanding cognitive deficits in MCI therefore improving the diagnosis of MCI.
... /fnins. . about higher-order, associative regularities, depends on a hippocampo-neocortical dialogue, in which the hippocampus serves as a buffer, storing higher-order input configurations sufficiently long to allow build-up of extrahippocampal neural representations reflecting the regularities across temporally and spatially discontinuous inputs (Gordon Hayman et al., 1993;Rosenbaum et al., 2001;Manns et al., 2003;Bayley and Squire, 2005;Moscovitch et al., 2005;. Thus, on one hand, memories for statistical regularities, which are important for predicting behaviour in the long run, would acquire a neural representation that is relatively resistant to decay. ...
Substantial evidence suggests that sleep has a role in declarative memory consolidation. An influential notion holds that such sleep-related memory consolidation is associated with a process of abstraction. The neural underpinnings of this putative process are thought to involve a hippocampo-neocortical dialogue. Specifically, the idea is that, during sleep, the statistical contingencies across episodes are re-coded to a less hippocampus-dependent format, while at the same time losing configural information. Two previous studies from our lab, however, failed to show a preferential role of sleep in either episodic memory decontextualisation or the formation of abstract knowledge across episodic exemplars. Rather these processes occurred over sleep and wake time alike. Here, we present two experiments that replicate and extend these previous studies and exclude some alternative interpretations. The combined data show that sleep has no preferential function in this respect. Rather, hippocampus-dependent memories are generalised to an equal extent across both wake and sleep time. The one point on which sleep outperforms wake is actually the preservation of episodic detail of memories stored prior to sleep.
... Interestingly, while cortical and caudal activations increased after sleep (as compared to wake), recruitment of the hippocampus was decreased after sleep. This observation is consistent with the classical (albeit sometimes contentious) view that the hippocampus is a temporary waystation for newly acquired information before transferring it to the cortex for long-term storage (Dudai 1996;Squire and Zola-Morgan 1996;Dudai et al. 2015, but see Nadel andRosenbaum et al. 2001;Schapiro et al. 2019 for alternate and complementary views). It is thus possible that the memory trace following wake was still labile in the hippocampus, whereas following sleep or a nap, consolidation was accelerated, as reflected by reduced hippocampal recruitment at retest. ...
Sleep consolidates memory for procedural motor skills, reflected by sleep-dependent changes in the hippocampal-striatal-cortical network. Other forms of procedural skills require the acquisition of a novel strategy to solve a problem, which recruit overlapping brain regions and specialized areas including the caudate and prefrontal cortex. Sleep preferentially benefits strategy and problem-solving skills over the accompanying motor execution movements. However, it is unclear how acquiring new strategies benefit from sleep. Here, participants performed a task requiring the execution of a sequence of movements to learn a novel cognitive strategy. Participants performed this task while undergoing fMRI before and after an interval of either a full night sleep, a daytime nap, or wakefulness. Participants also performed a motor control task, which precluded the opportunity to learn the strategy. In this way, we subtracted motor execution-related brain activations from activations specific to the strategy. The sleep and nap groups experienced greater behavioral performance improvements compared to the wake group on the strategy-based task. Following sleep, we observed enhanced activation of the caudate in addition to other regions in the hippocampal-striatal-cortical network, compared to wakefulness. This study demonstrates that sleep is a privileged time to enhance newly acquired cognitive strategies needed to solve problems.
... preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this . http: //dx.doi.org/10.1101/2019.12.19.881615 doi: bioRxiv preprint first posted online Dec. 19, 2019; Rosenbaum et al., 2001;Gilboa et al., 2004;Meeter and Murre, 2004;Moscovitch et al., 2005;Rekkas and Constable, 2005). Here, remote memories retain rich contextual detail (Suzuki and Naya, 2011) as long as the trace in the HPC is dominant at the time of retrieval. ...
Systems consolidation (SC) theory proposes that recent, contextually rich memories are stored in the hippocampus (HPC). As these memories become remote, they are believed to rely more heavily on cortical structures within the prefrontal cortex (PFC), where they lose much of their contextual detail and become schematized. Odor is a particularly evocative cue for intense remote memory recall and despite these memories being remote, they are highly contextual. In instances such as post-traumatic stress disorder (PTSD), intense remote memory recall can occur years after trauma, which seemingly contradicts SC. We hypothesized that odor may shift the organization of salient or fearful memories such that when paired with an odor at the time of encoding, they are delayed in the de-contextualization process that occurs across time, and retrieval may still rely on the HPC, where memories are imbued with contextually rich information, even at remote time points. We investigated this by tagging odor- and non-odor-associated fear memories in male c57BL/6 mice and assessed recall and c-Fos expression in the dorsal CA1 (dCA1) and prelimbic cortex (PL) 1 d or 21 d later. In support of SC, our data showed that recent memories were more dCA1-dependent whereas remote memories were more PL-dependent. However, we also found that odor influenced this temporal dynamic biasing the memory system from the PL to the dCA1 when odor cues were present. Behaviorally, inhibiting the dCA1 with activity-dependent DREADDs had no effect on recall at 1 d and unexpectedly caused an increase in freezing at 21 d. Together, these findings demonstrate that odor can shift the organization of fear memories at the systems level.
... Historically, research has focused on contextual and recognition memory in rodents and primates (Frankland and Bontempi 2005;Eichenbaum et al. 2007; Wang and Morris 2010) and episodic memory in humans (Tulving and Markowitsch 1998;Squire and Wixted 2010;Moscovitch et al. 2016). Despite substantial interest in the neural circuits that support navigation, there has been little systematic investigation directly comparing consolidated spatial memories and representations of environments learned long ago ("familiar" environments) with those learned recently (Rosenbaum et al. 2001;Spiers and Maguire 2007a;Winocur et al. 2010). This dearth of research is particularly surprising considering that current theories disagree about the contribution of the hippocampus to processing spatial representations over time: the standard consolidation theory (SCT) argues that initially the hippocampus is involved in processing the spatial memories, and that over time the representations in neocortical regions are strengthened, reducing the demand on the hippocampus (Squire 1992;Squire and Zola-Morgan 1998). ...
Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (>2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation.
... Despite substantial interest in the neural circuits that support navigation, little research has explored consolidation of spatial memories and representations of environments learned months or years ago ("familiar" environments) (8)(9)(10). This dearth of research is particularly surprising considering that current theories disagree about the contribution of the hippocampus to processing spatial representations over time: the standard consolidation theory (SCT) argues that initially the hippocampus is involved in processing the spatial memories and representations, and that over time the representations in neocortical regions are strengthened, reducing the demand on the hippocampus (11,12). ...
Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (> 2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the proximity to the goal in the newly learned campus, but not in the familiar campus. By contrast retrosplenial cortex tracked the distance to the goal in the familiar campus, but not in the recently learned campus. These responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and help advance models of how neural circuits support navigation in novel and highly familiar environments.
Significance Statement
Historically, research on the hippocampal formation has focused on its role in long-term memory and navigation – often in isolation. No study to date has directly compared realistic navigation within familiar with recently learned environments, nor has it been explored how the neural substrates, along with computational codes, may change. In this study, we show for the first time, a shift from hippocampal to cortical coding of distance to a goal during active navigation. This study bridges the gap between memory consolidation and navigation, and paves the way for more functional and realistic understanding of the hippocampus.
... This was supported by a study by Fader et al. (1999) that demonstrated that estrogen improves spatial working memory, but not reference memory. Thus, although the enhancing effects of estrogen on hippocampal-dependent memory are well documented (Josselyn et al., 2015;Rosenbaum et al., 2001;Winocur et al., 2013), estrogen's effects on other types of memory are less clear. ...
The role of sex and estrous phase in the conditioning of toxin-induced disgust reactions (anticipatory nausea) to a novel context were examined in adult rats. Conditioned oral gaping responses have been shown to be a reliable index of nausea in rats. In Experiment 1 male and female rats were injected with LiCl (0, 64, 96, or 128 mg/kg) on each of 4 conditioning trials (72 h apart) and then placed in a novel context for 30 min. 72 h following the last conditioning trial each animal was re-exposed to this context in a toxin-free state for 10 min and disgust responses (gapes, forelimb flails, chin rubs, and paw treads) were scored from video records. A significant toxin dose-related monotonic increase in conditioned gaping showed a significantly greater increase in females, relative to males. In Experiment 2 female rats were conditioned, using the same paradigm, on either diestrus or proestrus days (trials 96 h apart) with LiCl (96 mg/kg) or saline control injections. Disgust responses were recorded on each of the 4 conditioning trials and a toxin-free test trial. Significant increases in conditioned disgust were obtained on proestrus relative to diestrus days on the toxin-free test trial. However no significant estrous cycle differences in disgust responding were obtained on the acquisition trials. The sex difference in conditioned gaping and the increased conditioned disgust responses in proestrus suggest that increased levels of estradiol likely enhance the strength of the association of the toxin-induced nausea with the novel context in rats.
... The 'standard' theory of consolidation proposes that autobiographical memory traces are transferred over time, via 'systems consolidation,' into neocortical locations in which they become independent of the hippocampi (e.g., Squire and Bayley, 2007). In contrast, the multiple trace theory (MTT) suggests the hippocampal complex is involved life-long in the evocation of rich autobiographical memories (e.g., Moscovitch et al., 2005;Rosenbaum et al., 2001). At first sight, the uniform impairment of autobiographical memories extending across the entire lifespan appears more in line with the predictions of MTT. ...
Transient epileptic amnesia (TEA) is characterized by brief, recurrent episodes of transient amnesia occurring as a result of epilepsy. During these episodes, declarative memory is impaired while other cognitive functions remain intact. TEA is a syndrome of mesial temporal lobe epilepsy (TLE), which typically affects middle-aged people, particularly men. The amnesic attacks often occur on waking and can be accompanied by other symptoms of TLE such as automatisms, olfactory hallucinations, and short periods of unresponsiveness. EEG may reveal interictal epileptiform activity arising from the temporal lobes. Gross structural abnormalities are rarely observed, but group studies reveal subtle volume loss in hippocampal, perirhinal, and orbitofrontal cortices. The amnesic seizures respond very well to anticonvulsant medication, though most patients (around 80%) report interictal memory problems such as accelerated long-term forgetting (ALF), autobiographical, and topographical memory loss. These often persist despite successful treatment of the epilepsy. ALF, which is reported by around 50% of patients with TEA, involves the rapid forgetting of newly acquired information, occurs within 24 h of acquisition, and is likely to reflect a deficit in early memory consolidation or subtle impairments in memory acquisition. The autobiographical memory loss, seen in around two-thirds of patients with TEA, appears to be due to a degradation of established memories, though impairments of acquisition, consolidation, and retrieval may also play a part. These interictal memory difficulties are likely to result from either subtle structural damage in the medial temporal lobes or physiological disruption of memory processing by subclinical epileptiform activity.
... There is little dispute that the hippocampus is involved in some aspects of learning and memory, however it is important to acknowledge that not all researchers agree on the degree of hippocampal involvement in learning and memory. The nuances and complexities are beyond the scope of this review and the reader is directed to many excellent reviews on the topic (Josselyn et al., 2015;Leal and Yassa, 2015;Rosenbaum et al., 2001;Winocur et al., 2013). Certainly a large amount of evidence, including the existence of place and grid cells, points to a role of the hippocampus in spatial memory (Moser et al., 2015). ...
... consolidation (Rosenbaum et al., 2001). ...
CA1 is the main source of afferents from the hippocampus, but the function of
CA1 and its perforant path (PP) input remains unclear. In this thesis, Marr’s model
of the hippocampus is used to investigate previously hypothesized functions, and also
to investigate some of Marr’s unexplored theoretical ideas. The last part of the thesis
explains the excitatory responses to PP activity in vivo, despite inhibitory responses in
vitro.
Quantitative support for the idea of CA1 as a relay of information from CA3 to the
neocortex and subiculum is provided by constraining Marr’s model to experimental
data. Using the same approach, the much smaller capacity of the PP input by comparison
implies it is not a one-shot learning network. In turn, it is argued that the
entorhinal-CA1 connections cannot operate as a short-term memory network through
reverberating activity.
The PP input to CA1 has been hypothesized to control the activity of CA1 pyramidal
cells. Marr suggested an algorithm for self-organising the output activity during
pattern storage. Analytic calculations show a greater capacity for self-organised patterns
than random patterns for low connectivities and high loads, confirmed in simulations
over a broader parameter range. This superior performance is maintained in the
absence of complex thresholding mechanisms, normally required to maintain performance
levels in the sparsely connected networks. These results provide computational
motivation for CA3 to establish patterns of CA1 activity without involvement from the
PP input.
The recent report of CA1 place cell activity with CA3 lesioned (Brun et al., 2002.
Science, 296(5576):2243-6) is investigated using an integrate-and-fire neuron model
of the entorhinal-CA1 network. CA1 place field activity is learnt, despite a completely
inhibitory response to the stimulation of entorhinal afferents. In the model, this is
achieved using N-methyl-D-asparate receptors to mediate a significant proportion of
the excitatory response. Place field learning occurs over a broad parameter space. It is
proposed that differences between similar contexts are slowly learnt in the PP and as a
result are amplified in CA1. This would provide improved spatial memory in similar
but different contexts.
... En effet, elle comprend les informations relatives aux composantes « quoi » et « où » qui, associées au contexte temporel (le « quand »), définissent un souvenir de type épisodique OKeefe et Nadel, 1978 ;Burgess et al. 2002). Une analogie entre la mémoire humaine et animale a ainsi été proposée par Rosenbaum et al., pour qui les mémoires ooteetuelles hez laaial et pisodiue hez lHooe seeaiet oopaables (Rosenbaum et al. 2001). Il a également été suggéré que les représentations spatiales détaillées (associées à une expérience ihe e dtails su leeiooeeet) soient des analogues de la mémoire épisodique et e uel ue soit lâge du soueei oocerné), tandis que des représentations spatiales sshatiues, ooespoodat à u eseeele didies et de caractéristiques moins spécifiques, seraient des analogues de la mémoire sémantique chez lHooe (rev. ...
This thesis aimed to investigate the role of a circuit encompassing the hippocampus (Hip), the medial prefrontal cortex (mPFC) and the reuniens and rhomboid nuclei (ReRh) of the thalamus in cognitive processes underlying spatial memory in rats. We first showed that ReRh nuclei may be involved in systemic consolidation, a mechanism necessary for memory persistence and requiring hippocampal-cortical interactions. We confirmed these findings in a second study showing that mPFC neuronal activity during recall of a remote spatial memory depends on ReRh thalamic nuclei. We also showed the involvement of the ReRh nuclei in a mnemonic task requiring the use of both spatial information (dependent on the Hip) and behavioral flexibility (involving the mPFC). Finally, we found a role of the mPFC in the recall of recent spatial memory. Taken together, these results highlight the importance of a hippocampo-cortico-thalamic circuit in the processing and persistence of spatial information in the Rat.
... Remote spatial memories are represented by a larger number of traces and so can be more accessible than recently acquired memories. According to a later version of this model (Nadel & Bohbot, 2001;Rosenbaum et al., 2001), this multiple-trace theory applies particularly to "contextually rich" memories but not those that are context-free. ...
Spatial navigation is a complex function requiring the combination of external and self-motion cues to build a coherent representation of the external world and drive optimal behaviour directed towards a goal. This multimodal integration suggests that a large network of cortical and subcortical structures interacts with the hippocampus, a key structure in navigation. I have studied navigation in mice through this global approach and have focused on one particular type of navigation, which consists in remembering a sequence of turns, named sequence-based navigation or sequential egocentric strategy. This navigation specifically relies on the temporal organization of movements at spatially distinct choice points. We first showed that sequence-based navigation learning required the hippocampus and the dorsomedial striatum. Our aim was to identify the functional network underlying sequence-based navigation using Fos imaging and computational approaches. The functional networks dynamically changed across early and late learning stages. The early stage network was dominated by a highly inter-connected cortico-striatal cluster. The hippocampus was activated alongside structures known to be involved in self-motion processing (cerebellar cortices), in mental representation of space manipulations (retrosplenial, parietal, entorhinal cortices) and in goal-directed path planning (prefrontal-basal ganglia loop). The late stage was characterized by the emergence of correlated activity between the hippocampus, the cerebellum and the cortico-striatal structures. Conjointly, we explored whether path integration, model-based or model-free reinforcement learning algorithms could explain mice’s learning dynamics. Only the model-free system, as long as a retrospective memory component was added to it, was able to reproduce both the group learning dynamics and the individual variability observed in the mice. These results suggest that a unique model-free reinforcement learning algorithm was sufficient to learn sequence-based navigation and that the multiple structures this learning required adapted their functional interactions across learning.
... As previously described, the Transformation Hypothesis implies a role for the hippocampus in forming contextually bound detailed representations, whether spatial or non-spatial. The Transformation Hypothesis stemmed from K.C.'s difficulty representing detailed features of a well-known environment that he was otherwise able to navigate (Rosenbaum et al., 2000Rosenbaum et al., , 2001Rosenbaum et al., , 2005). Similar findings in healthy older individuals and other cases of hippocampal amnesia have substantiated these claims (Maguire et al., 2006; Rosenbaum et al., 2012). ...
... Retrograde amnesia is the loss of memories for events or information that was gained prior to the lesion. Both the existence and the duration of retrograde amnesia after hippocampal lesions has been hotly debated (Rosenbaum et al., 2001;Nestor et al., 2002). Haist et al. (2001) have used fMRI and the famous faces task to generate data indicating that the hippocampus proper may be involved only in the retrieval of memories that go back a few years. ...
This chapter focuses on the functional organization of the human hippocampal formation. It first discusses the gross anatomy of the hippocampal formation. The gross anatomical features of the hippocampal formation are taking on increasing importance as landmarks in neuroimaging studies. The chapter also deals with the cytoarchitetonic organization of the hippocampus with a comparison to the rodent and nonhuman primate. Next section deals with the connectivity of the hippocampal formation. Furthermore, the chapter presents an overview of normal development of the human hippocampal formation, followed by the discussion of pathological conditions that have a direct impact on human hippocampal formation. It necessarily provides an overview of this area because there has been an extensive research, both at the basic and clinical levels, dealing with topics such as Alzheimer's disease and the hippocampus. Finally, the last section surveys the results obtained with modern neuroimaging techniques and how they have influenced thinking about the function of the hippocampal formation.
... Chronic ethanol consumption can negatively affect central nervous system function and produce learning and memory impairment in animals and humans (1)(2)(3). The hippocampus, a region important for memory function, can recover from memory dysfunction caused by prolonged ethanol intake (4)(5)(6)(7). Electrophysiological, morphological and behavioral studies have shown that changes in the hippocampus can be induced by chronic alcohol intake (8,9). For the age group 15-64 years in the European Union, 3.4% of women and 15.3% of men are heavy drinkers, 1.5% of women and 5.4% of men have alcohol dependence, and 1 in 13 deaths in women and 1 in 7 deaths in men are caused by alcohol consumption (10). ...
Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.
... For example, hippocampal lesions studies showed impairment in a contextual fear-conditioning task for recently acquired fear whereas no deficit was observed for a conditioning to unimodal stimuli (a tone, this task involved mainly amygdala not the dorsal hippocampus) or to remotely acquired fear (Kim and Fanselow, 1992). Rosenbaum and colleagues (2001) argued that tests dependent on relational context like the contextual fear conditioning task (analogous to episodic memories in humans) are impaired by hippocampal lesions whereas, tests that are less dependent on relational context like the tone-shock association (analogous to semantic memories in humans) are not disrupted (Rosenbaum et al., 2001). ...
For many years, scientists have been investigating the neural bases of memory. However, a key question remains unanswered: how does the brain distinguish information important enough to be consolidated into long-term memory from information required only temporarily, and that needs to be cleared away for not saturating our cognitive resources. In contrast to the popular view considering forgetting as deleterious to our ability to remember, forgetting might be an essential adaptive process allowing the filtering of non-essential information. Surprisingly, very little is known on the cellular and molecular bases of adaptive forgetting. The work presented in this thesis aims to find a way to determine such bases of adaptive forgetting, in particular in the context of Working Memory processing. With this thesis, we thus showed that the dentate gyrus is a critical node in processing the forgetting of irrelevant information, an essential process allowing optimal use of cognitive resources. Our work sheds light not only on the question of how the brain responds to interferences, but also on the mechanisms of "forgetting" what should be forgotten
... The prefrontal cortex and hippocampus are mostly associated with age-related cognitive decline in human and primates (Paulesu et al. 1993;Levy and Goldman-Rakic 1999). Moreover, the hippocampus is the brain structure known to change first during normal aging (Geinisman et al. 1995;Winocur and Gagnon 1998), which has been observed behaviorally as a change in hippocampus-dependent cognitive performance in rodents and humans (Rapp et al. 1997;Maguire and Cipolotti 1998;Rosenbaum et al. 2001). ...
Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed. In the present study, we have examined the age-related changes in the expression of these proteins in cerebral cortex and hippocampus of 10-, 30-, 50-, and 80-week-old male mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated that messenger RNA (mRNA) level of Nrxn1 and Nlgn3 significantly increased from 10 to 30 weeks and then decreased at 50 weeks in both the regions. However, in 80-week-old mice, Nrxn1 and Nlgn3 were further downregulated in cerebral cortex while Nrxn1 was downregulated and Nlgn3 was upregulated in hippocampus. These findings were corroborated by immunoblotting and immunofluorescence results. When the expression of Nrxn1 and Nlgn3 was correlated with presynaptic density marker synaptophysin, it was found that synaptophysin protein expression in cerebral cortex was high at 10 weeks and decreased gradually up to 80 weeks, whereas in hippocampus, it decreased until 50 weeks and then increased remarkably at 80 weeks. Furthermore, Pearson's correlation analysis showed that synaptophysin had a strong relation with Nrxn1 and Nlgn3 in cerebral cortex and with Nlgn3 in hippocampus. Thus, these findings showed that Nrxn1 and Nlgn3 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during aging.
... Moreover, although the amnesic cases' prospective narratives were relatively impoverished, other than K.C., they were not at floor and retained sparse, gist-like content. In this sense, episodic prospection in amnesia mirrors amnesic individuals' abilities in episodic or spatial memories in which detail and specificity are compromised, whereas broad, gist-like representations tend to be better preserved (see Rosenbaum et al., 2001). Thus, it is possible that presentation of future event cues activates gist representations of future experiences that are sufficient to modulate decisions regarding the future, even in the absence of detailed event construction. ...
How does the ability to imagine detailed future experiences (i.e., episodic prospection) contribute to choices between immediate and delayed rewards? Individuals with amnesia do not show abnormally steep discounting in intertemporal choice, suggesting that neither medial temporal lobe (MTL) integrity nor episodic prospection is required for the valuation of future rewards (Kwan et al., 2012, 2013). However, hippocampally mediated episodic prospection in healthy adults reduces the discounting of future rewards (Peters and Büchel, 2010; Benoit et al., 2011), raising the possibility that MTL damage causes more subtle impairments to this form of decision-making than noted in previous patient studies. Intertemporal choice appears normal in amnesic populations, yet they may be unable to use episodic prospection to adaptively modulate the value assigned to future rewards. To investigate how the extended hippocampal system, including the hippocampus and related MTL structures, contributes to the valuation of future rewards, we compared the performance of six amnesic cases with impaired episodic prospection to that of 20 control participants on two versions of an intertemporal choice task: a standard discounting task, and a cued version in which cues prompted them to imagine specific personal future events temporally contiguous with the receipt of delayed rewards. Amnesic individuals' intertemporal choices in the standard condition were indistinguishable from those of controls, replicating previous findings. Surprisingly, performance of the amnesic cases in the cued condition indicates that amnesia does not preclude flexible modulation of choices in response to future event cues, even in the absence of episodic prospection. Cueing the personal future to modulate decisions appears to constitute a less demanding or a qualitatively different (e.g., personal semantic) form of prospection that is not as sensitive to MTL damage as prospective narrative generation. This article is protected by copyright. All rights reserved.
© 2015 Wiley Periodicals, Inc.
In two freestanding volumes, the Textbook of Neural Repair and Rehabilitation provides comprehensive coverage of the science and practice of neurological rehabilitation. Revised throughout, bringing the book fully up to date, this volume, Neural Repair and Plasticity, covers the basic sciences relevant to recovery of function following injury to the nervous system, reviewing anatomical and physiological plasticity in the normal central nervous system, mechanisms of neuronal death, axonal regeneration, stem cell biology, and research strategies targeted at axon regeneration and neuron replacement. New chapters have been added covering pathophysiology and plasticity in cerebral palsy, stem cell therapies for brain disorders and neurotrophin repair of spinal cord damage, along with numerous others. Edited and written by leading international authorities, it is an essential resource for neuroscientists and provides a foundation for the work of clinical rehabilitation professionals.
Autobiographical memory represents a defining feature of human cognition, enabling us to vividly re‐experience salient events from the personal past. By mentally traversing different temporal contexts, humans can maintain an enduring sense of who we are as individuals, as well as envisaging our future goals and behaviors. The relative ease with which we engage in these endeavors, however, belies the remarkable complexity of the autobiographical memory system. Dementia syndromes offer compelling insights into the cognitive neuroarchitecture of autobiographical memory in the face of progressive neural insult to large‐scale brain networks. Importantly, the atrophy profiles of many neurodegenerative disorders follow coordinated and predictable trajectories, affecting key regions implicated in episodic and semantic memory. A wealth of evidence suggests that autobiographical memory disruption is a transdiagnostic feature of dementia, yet this impairment takes many forms and arises due to differential neurocognitive disturbances. This review aims to provide a comprehensive overview of the literature on autobiographical memory in typical and atypical presentations of Alzheimer's disease, as well as younger‐onset dementia syndromes such as frontotemporal dementia and primary progressive aphasia. I will demonstrate how the systematic study of autobiographical memory across dementia syndromes can constrain and inform our fundamental understanding of memory function and, in turn, stimulate new directions in how we conceptualize and assess these cognitive capacities. Consideration will further be given to clinical implications of autobiographical memory dysfunction with a view to developing targeted interventions to better support the person living with dementia.
This article is categorized under: Psychology > Memory
Neuroscience > Clinical Neuroscience
Psychology > Brain Function and Dysfunction
La théorie standard de la consolidation postule que l’information est initialement encodée dans le réseau hippocampo-cortical, créant une trace mnésique au sein de l’hippocampe (HIP). Au cours du temps, la trace est transférée au cortex préfrontal médian (CPFm), et notamment au cortex cingulaire antérieur (CCA). À la suite de lésion des noyaux reuniens et rhomboide (ReRh), réciproquement connectés à l’HIP et au CPFm, le souvenir spatial se forme normalement mais ne persiste pas dans le temps. Ainsi, nous avons évalué l’impact de la lésion ReRh sur la plasticité structurale sous-tendant la persistance du souvenir spatial. Des rats lésés ReRh ont été entraînés en piscine de Morris et testés pour un rappel récent (5j) ou ancien (25j). La plasticité structurale a été évaluée par coloration de Golgi dans l’HIP et le CPFm. La lésion ReRh n'avait aucun effet sur l’apprentissage et le souvenir récent, mais a altéré celui du souvenir ancien. Dans le CA1 des rats Sham, le nombre d'épines dendritiques a été augmenté aux deux délais (5 et 25j) post-acquisition comparé au niveau basal. Après la lésion, cette augmentation n’a pas persisté entre 5 et 25j. Dans le CCA des rats Sham, le nombre d'épines dendritiques a été augmenté uniquement à 25j comparé au niveau de base, une modification non observée chez les rats lésés. Ainsi, à la lésion des noyaux ReRh perturbe la plasticité structurale sous-tendant le souvenir spatial ancien indiquant un rôle crucial de ces noyaux dans l’établissement d’un souvenir persistant.
Kent Cochrane (K.C.) has been investigated by researchers for nearly three decades after intracranial trauma from a motorcycle accident at age 30 resulted in a striking profile of amnesia. K.C. suffered severe anterograde amnesia in both verbal and non-verbal domains which was accompanied by selective retrograde amnesia for personal events experienced prior to the time of his injury (episodic memory), with relative preservation of memory for personal and world facts (semantic memory), and of implicit memory. This pattern of spared and impaired memory extended to spatial memory for large-scale environments and beyond memory to future imagining and decision-making. Post-mortem brain findings at age 62 included moderate diffuse atrophy, left orbitofrontal contusion, left posterior cerebral artery infarct, and left anterior frontal watershed infarct. Notably, there was severe neuronal loss and gliosis of the hippocampi bilaterally. The left hippocampus was severely affected anteriorly and posteriorly, but CA2, CA4, and the dentate gyrus (DG) were focally spared. There was associated degeneration of the left fornix. The right hippocampus showed near complete destruction anteriorly, with relative preservation posteriorly, mainly of CA4 and DG. Bilateral parahippocampal gyri and left anterior thalamus also showed neuron loss and gliosis. There was no evidence of co-existing neurodegenerative phenomena on beta-amyloid, phosphorylated tau, or TDP-43 immunostaining. The extent of damage to medial temporal lobe structures is in keeping with K.C.'s profound anterograde and retrograde amnesia, with the exception of the unexpected finding of preserved CA2/CA4 and DG. K.C.'s case demonstrates that relatively clean functional dissociations are still possible following widespread brain damage, with structurally compromised brain regions unlikely to be critical to cognitive functions found to be intact. In this way, the findings presented here add to K.C.'s significant contributions to our understanding of clinical-anatomical relationships in memory.
Cognitive control refers to brain processes involved in regulating behavior according to internal goals or plans. This study examines whether hippocampal connectivity with sensorimotor cortex during paced movements shows a pattern of spatial and temporal selectivity required for cognitive control. Functional magnetic resonance imaging activity was recorded from thirteen right-handed subjects during a paced, non-mnemonic (repetitive tapping) motor task. Connectivity was examined from psychophysiological interactions in hippocampal activity during two analyses: the first identified motor interactions relative to rest, whereas the second identified differential motor activity between adjacent fingers. Connectivity was observed in both pre- and postcentral gyrus, but only postcentral connectivity was topographical, coincident with finger representations identified in a previous study. Differences in the magnitude of connectivity were observed between finger representations, representing spatial selectivity for the target of movements; the postcentral representation of the moving finger invariably showed greater connectivity than adjacent fingers. Furthermore, the magnitude of connectivity within a pre- or postcentral finger representation was largest when its finger moved, representing temporal selectivity for movement. While the hippocampus is known to be sensitive to spatial and temporal features of the environment, consistent with its role in learning and memory, the pattern of spatial and temporal selectivity of hippocampal connectivity observed in this study occurred during volitional movements in the absence of motor learning or recall. Spatial and temporal selectivity of connectivity during volitional movements meets the criteria for cognitive control adapted from oculomotor studies, suggesting a role for the hippocampus in motor control.
Memories are complex and dynamic, continuously transforming with time and experience. In this paper, we review evidence of the neural basis of memory transformation for events and environments with emphasis on the role of hippocampal–neocortical interactions. We argue that memory transformation from detail-rich representations to gist-like and schematic representation is accompanied by corresponding changes in their neural representations. These changes can be captured by a model based on functional differentiation along the long-axis of the hippocampus, and its functional connectivity to related posterior and anterior neocortical structures, especially the ventromedial prefrontal cortex (vmPFC). In particular, we propose that perceptually detailed, highly specific representations are mediated by the posterior hippocampus and neocortex, gist-like representations by the anterior hippocampus, and schematic representations by vmPFC. These representations can co-exist and the degree to which each is utilized is determined by its availability and by task demands.
Much of the richness in human life derives from episodic memory, mental representations of detailed experiences from our personal pasts. To make sense of those experiences, knowledge about the world and oneself must also exist in a form that is free of context – known as semantic memory. This chapter revisits and builds on Tulving's distinction between episodic and semantic memory, with a focus on their differences, similarities, and interactions, informed by cognitive, neuropsychological, and neuroimaging studies. Extensions of this distinction into spatial memory, and beyond memory into future thinking, are considered in the context of process views of memory organization.
Functions of the different cortical parts of the brain are mediated by the widespread white matter networks that connect the different parts of the brain. With the advent of diffusion tensor imaging (DTI), it is now possible to visualize the larger of these white matter tracts.
Generalization of fear responses is a symptom of many anxiety disorders and we have previously demonstrated that female rats generalize fear to a neutral context at a faster rate compared to males. This effect is due in part, to activation of ER and modulation of memory retrieval mechanisms resulting in fear generalization. Given that the effects of estradiol on fear generalization required approximately 24 h, our data suggested possible genomic actions on fear generalization. To determine whether these actions were due to cytosolic versus membrane bound receptors, female rats were given infusions of ICI 182,780, a cytosolic estrogen receptor antagonist, into the lateral ventricle or dorsal hippocampus simultaneously with estradiol treatment or with an ER agonist (DPN). Infusions of ICI into the lateral ventricle or the dorsal hippocampus blocked fear generalization induced by peripheral or central treatment with estradiol or DPN, suggesting that estradiol acts through cytosolic ERβ receptors. In further support of these findings, intracerebroventricular or intra-hippocampal infusions of bovine serum conjugated estradiol (E2-BSA), activating membrane-bound estrogen receptors only, did not induce fear generalization. Moreover, rats receiving intra-hippocampal infusions of the ERK/MAPK inhibitor, U0126, continued to display estradiol-induced generalization, again suggesting that membrane-bound estrogen receptors do not contribute to fear generalization. Overall, these data suggest that estradiol-induced enhancements in fear generalization are mediated through activation of cytosolic/nuclear ER within the dorsal hippocampus. This region seems to be an important locus for the effects of estradiol on fear generalization although additional neuroanatomical regions have yet to be identified.
Mastering the Morris water maze (MWM) requires the animal to consolidate, retain and retrieve spatial localizations of relevant visual cues. However, it is necessary to investigate whether a reorganization of the neural networks takes place when part of the spatial information is removed. We conducted four experiments using the MWM. A classical reference memory procedure was performed over five training days, RM5 (n=7), and eight days, RM8 (n=7), with the whole room and all the spatial cues presented. Another group of animals were trained in the same protocol, but they received an additional day of training with only partial cues, PC (n=8). Finally, a third group of animals performed the classical task, followed by an overtraining with partial cues for four more days, OPC (n=8). After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. In addition, c-Fos positive cells were measured in the RM5, RM8, PC and OPC groups. No significant differences were found among the four groups in escape latencies or time spent in the target quadrant. CO revealed involvement of the prefrontal and parietal cortices, dorsal and ventral striatum, CA1 and CA3 subfields of the dorsal hippocampus, basolateral and lateral amygdala, and mammillary nuclei in the PC group, compared to the RM group. In the OPC group, involvement of the ventral striatum and anteroventral thalamus and the absence of amygdala involvement were revealed, compared to the PC group. C-Fos results highlighted the role of the prefrontal cortex, dorsal striatum, anterodorsal thalamus and CA3 in the PC group, compared to the OPC, RM5 and RM8 groups. The animals were able to find the escape platform even when only a portion of the space where the cues were placed was available. Although the groups did not differ behaviorally, energetic brain metabolism and immediate early gene expression revealed the engagement of different neural structures in the groups that received more training without the entire surrounding space.
Copyright © 2015. Published by Elsevier B.V.
Amnesia is a neurobehavioral syndrome characterized by a selective impairment in memory in the context of preserved intelligence and other cognitive abilities. Permanent amnesia can be caused by a range of etiologies that damage neural structures in the limbic system or the basal forebrain. Amnesic patients are impaired at acquiring new information (anterograde amnesia) and can also be impaired at retrieving information acquired prior to the onset of amnesia (retrograde amnesia). The clinical features of anterograde and retrograde amnesia are an important source of information about the cognitive and neural architecture of memory systems.
Although investigations into the functional and anatomical organization of language within the human brain began centuries ago, it is recent advanced imaging techniques including functional magnetic resonance imaging and diffusion tensor imaging that have helped propel our understanding forward at an unprecedented rate. Important cortical brain regions and white matter tracts in language processing subsystems including semantic, phonological, and orthographic functions have been identified. An understanding of functional and dysfunctional language anatomy is critical for practicing radiologists. This knowledge can be applied to routine neuroimaging examinations as well as to more advanced examinations such as presurgical brain mapping.
Copyright © 2015 Elsevier Inc. All rights reserved.
Neurodegenerative disorders offer a compelling view of the cognitive architecture of the brain when specific neural systems break down in a coordinated fashion. The study of neurodegenerative cohorts can therefore provide important insights into the underlying mechanisms supporting episodic memory. In this chapter, we examine the systematic and progressive degeneration of episodic memory processes in the most common subtypes of dementia, namely Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We discuss behavioral and neuroimaging studies of anterograde and retrograde episodic memory deficits in these dementia subtypes, as well as recent advances in which the ability to imagine the future is posited to represent a key expression of the episodic memory system.
Memory formation is a protracted process in which recently acquired events are consolidated to produce stable and specific associations. Initially, newly acquired information undergoes cellular consolidation in the hippocampus, which transiently supports the storage of recently acquired memories. In contrast, remote, or "old" memories are maintained in the cortex and show almost complete independence from the hippocampus. Memories are transferred from the hippocampus to the cortex through a process termed systems consolidation. Emerging evidence suggests that recurrent activation, or "training" of the cortex by the hippocampus is vital to systems consolidation. This process involves prolonged waves of memory-related gene activity in the hippocampus and cortex long after the learning event has terminated. Indeed, molecular events occurring within hours and days of fear conditioning are essential for stabilizing and eventually transitioning the memory to the cortex. It is increasingly evident that molecular mechanisms that exhibit a capacity for prolonged activation may underlie systems consolidation. Processes that have the capacity to control protein abundance over long time scales, such as epigenetic modifications, are prime candidates for the molecular mechanism of systems consolidation. Indeed, recent work has established two types of epigenetic modifications as integral for systems consolidation. First, localized nucleosomal histone variant exchange and histone modifications are integral for early stages of systems consolidation, whereas DNA methylation appears to be utilized to form stable marks that support memory maintenance. Since systems consolidation also requires discrete and time sensitive changes in protein abundance, additional mechanisms, such as protein degradation, need also be considered, although their role in systems consolidation has yet to be investigated. Here, we discuss the role of molecular mechanisms in systems consolidation and their implications for understanding how memories persist over time.
Copyright © 2015. Published by Elsevier Ltd.
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.
Two patients with presumed hippocampal formation lesions and two patients with more extensive temporal lobe damage, all of whom became amnesic in a known year, were given tests of anterograde and retrograde memory function. The two patients with hippocampal formation lesions had moderately severe anterograde amnesia and limited retrograde amnesia for facts and events that affected, at most, the decade preceding the onset of amnesia. Content analysis could not distinguish the autobiographical recollections of the patients from the recollections of control subjects. The two patients with more extensive temporal lobe damage had severe anterograde amnesia and extensive retrograde memory loss for both facts and events. The results suggest that whether retrograde amnesia is temporally limited or very extensive depends on whether the damage is restricted to the hippocampal formation or also involves additional temporal cortex.
During the past 100 years clinical studies of amnesia have linked memory impairment to damage of the hippocampus. Yet the damage in these cases has not usually been confined to the hippocampus, and the status of memory functions has often been based on incomplete neuropsychological information. Thus, the human cases have until now left some uncertainty as to whether lesions limited to the hippocampus are sufficient to cause amnesia. Here we report a case of amnesia in a patient (R.B.) who developed memory impairment following an ischemic episode. During the 5 years until his death, R.B. exhibited marked anterograde amnesia, little if any retrograde amnesia, and showed no signs of cognitive impairment other than memory. Thorough histological examination revealed a circumscribed bilateral lesion involving the entire CA1 field of the hippocampus. Minor pathology was found elsewhere in the brain (e.g., left globus pallidus, right postcentral gyrus, left internal capsule), but the only damage that could be reasonably associated with the memory defect was the lesion in the hippocampus. To our knowledge, this is the first reported case of amnesia following a lesion limited to the hippocampus in which extensive neuropsychological and neuropathological analyses have been carried out.
Studies of patients and animals with brain lesions have implicated the hippocampal formation in
spatial, declarative/relational and episodic types of memory. These and other types of memory consist
of a series of interdependent but potentially dissociable memory processes—encoding, storage,
consolidation and retrieval. To identify whether hippocampal activity contributes to these processes
independently, we used a novel method of inactivating synaptic transmission using a water-soluble
antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and
two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal
hippocampus of rats at appropriate times during or after training in a water maze. Our findings
indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial
memory and for either trace consolidation or long-term storage.
Memory consolidation refers to the idea that neurophysiological processes occurring after the initial registration of information contribute to the permanent storage of memory. This idea has been supported by the phenomenon of temporally graded (or temporally limited) retrograde amnesia, in which information acquired recently is more affected than information acquired longer ago. It is an important, yet open issue at present, how memory consolidation occurs in the brain. Retrograde amnesia (RA), the inability to retrieve information acquired prior to the onset of brain damage, is sometimes extensive enough to cover a patient's whole lifetime, or sometimes temporally limited. Typically, RA is caused by damage to the medial temporal lobe, the diencephalon, and the basal forebrain. As far as the temporal lobe is concerned, however, RA results from damage not only to medial temporal regions, but also to other regions in the temporal lobe with or without damage to the medial temporal region. To gain a better understanding of memory consolidation processes and RA after damage to the temporal lobe, we will review studies on amnesia after temporal lobe lesions in terms of lesion profile and the nature/extent of RA. In this chapter, we first review data on RA after damage to the temporal lobe in humans. Then, we review the relevant literature from the study of memory consolidation in animal models. Finally, we propose a possible model of memory consolidation based on the data available to date. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Conducted 4 experiments to assess autobiographical memory in 5 normal Ss (mean age 53.8 yrs) and in 5 memory-impaired patients (47–65 yrs old), all of whom had become amnesic on a known date. The patients were unable to produce autobiographical recollections in as much detail as the normal Ss could. Impairment was especially noticeable when single-word cues were used to elicit memories and when Ss were asked to recollect events from any past time period. Amnesic patients performed better when they restricted their recollections to childhood or adolescence. Patients who had the most difficulty recollecting also exhibited the most severe and extensive retrograde amnesia on fact-memory tests. Findings do not support the view that amnesia especially affects episodic, as compared with semantic, memory. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
A recent report by Cipolotti et al. demontrates that the hippocampus and perhaps the parahippocampal area are essential for retrieval of remote episodic memory and important for remote semantic memory. This report, along with other recent findings, re-opens the debate about the role of these medial temporal lobe structures, indicating that their role extends much further than traditional theory had suggested.
For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.
Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.
This article reviews recent studies of memory systems in humans and nonhuman primates. Three major conclusions from recent work are that (i) the capacity for nondeclarative (nonconscious) learning can now be studied in a broad array of tasks that assess classification learning, perceptuomotor skill learning, artificial grammar learning, and prototype abstraction; (ii) cortical areas adjacent to the hippocampal formation, including entorhinal, perirhinal, and parahippocampal cortices, are an essential part of the medial temporal lobe memory system that supports declarative (conscious) memory; and (iii) in humans, bilateral damage limited to the hippocampal formation is nevertheless sufficient to produce severe anterograde amnesia and temporally graded retrograde amnesia covering as much as 25 years.
Emotional responses such as fear are rapidly acquired through classical conditioning. This report examines the neural substrate
underlying memory of acquired fear. Rats were classically conditioned to fear both tone and context through the use of aversive
foot shocks. Lesions were made in the hippocampus either 1, 7, 14, or 28 days after training. Contextual fear was abolished
in the rats that received lesions 1 day after fear conditioning. However, rats for which the interval between learning and
hippocampal lesions was longer retained significant contextual fear memory. In the same animals, lesions did not affect fear
response to the tone at any time. These results indicate that fear memory is not a single process and that the hippocampus
may have a time-limited role in associative fear memories evoked by polymodal (contextual) but not unimodal (tone) sensory
stimuli.
This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans--which has sometimes seemed to proceed independently in 3 separate literatures--is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.
Rabbits (Oryctolagus cuniculus) with lesions to either the hippocampus or overlying neocortex and unoperated controls underwent acquisition of the classically conditioned nictitating membrane response to a tone conditioned stimulus and an air puff unconditioned stimulus until they reached a criterion of 8 conditioned responses in any block of 10 trials. They were then returned to their cages. On the next day, they were either placed in the same context in which they underwent initial conditioning or switched to a new context that distinctly differed along olfactory, visual, and tactile dimensions. In relation to unswitched controls, rabbits with lesions to the neocortex and unoperated controls showed a disruption of conditioning when contexts were switched. In contrast, rabbits with lesions to the hippocampus performed at the same levels as unswitched controls. The results are discussed in terms of the possible role of hippocampus in coding context in classical conditioning.
The role of the hippocampus in associative learning was investigated in 3 experiments with rats as subjects. Hippocampal rats were impaired in the acquisition of conditioned responding both when food was signaled by the insertion of a lever (Experiment 1) and when the presentation of auditory or visual events served as the conditioned stimuli (Experiment 2). Experiment 2 also evaluated the suggestion that deficits in the acquisition of conditioned responding reflect the failure of hippocampal subjects to use contextual cues to retrieve associative information. This experiment showed that hippocampal rats were impaired in learning that a given stimulus was reinforced in Context A but nonreinforced in Context B. Experiment 3 demonstrated that hippocampal rats were unimpaired in learning a simple Pavlovian contextual discrimination. This pattern of results suggests that the hippocampus is involved in a higher order contextual retrieval process.
Clinical and experimental studies have shown that the hippocampal formation and related structures in the medial temporal
lobe are important for learning and memory. Retrograde amnesia was studied prospectively in monkeys to understand the contribution
of the hippocampal formation to memory function. Monkeys learned to discriminate 100 pairs of objects beginning 16, 12, 8,
4, and 2 weeks before the hippocampal formation was removed (20 different pairs at each time period). Two weeks after surgery,
memory was assessed by presenting each of the 100 object pairs again for a single-choice trial. Normal monkeys exhibited forgetting;
that is, they remembered recently learned objects better than objects learned many weeks earlier. Monkeys with hippocampal
damage were severely impaired at remembering recently learned objects. In addition, they remembered objects learned long ago
as well as normal monkeys did and significantly better than they remembered objects learned recently. These results show that
the hippocampal formation is required for memory storage for only a limited period of time after learning. As time passes,
its role in memory diminishes, and a more permanent memory gradually develops independently of the hippocampal formation,
probably in neocortex.
Recent single-case studies have attempted to identify the cognitive processes contributing to autobiographical amnesia (and more generally to retrograde amnesia) by contrasting preserved and impaired functions. They have contributed to support and question the episodic/semantic distinction as well as the episodic/semantic interpretation of amnesia. They suggest that autobiographical memories (and also public knowledge) are composed of different types of information that can be accessed through different routes. They also corroborate data from studies on normal subjects which showed that autobiographical factual knowledge might be associated with semantic knowledge and that public knowledge might intersect with personal memories
Recent single-case studies have attempted to identify the cognitive processes contributing to autobiographical amnesia (and more generally to retrograde amnesia) by contrasting preserved and impaired functions. They have contributed to support and question the episodic/semantic distinction as well as the episodic/semantic interpretation of amnesia. They suggest that autobiographical memories (and also public knowledge) are composed of different types of information that can be accessed through different routes. They also corroborate data from studies on normal subjects which showed that autobiographical factual knowledge might be associated with semantic knowledge and that public knowledge might intersect with personal memories.
Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.
It has often been assumed that memory depends upon the total action of the brain rather than upon some specialized intracerebral neuron mechanism. There is recent evidence, however, in support of the view that the recording of experience is localizable in the same sense that sensory functions and speech functions are localizable. Obviously, none of these subdivisions is separable from the work of the brain as a whole.
The following study shows that the capacity to record the daily current of conscious experience may be lost when there is bilateral destruction of a man's hippocampus and hippocampal gyrus. Functional paralysis of this recording mechanism does not, however, interfere with the patient's intellectual performance in other psychological tests not dependent on recent memory. Skills, language, and all those things which have already been learned are not lost.
This inability to record new experience is not found in cases of strictly unilateral
Reports an error in the original article by L. R. Squire (Psychological Review, 1992[Apr], Vol 99[2], 195–231). The caption for Figure 7 was incorrect. The corrected caption is given. (The following abstract of this article originally appeared in record 1992-26428-001.) Considers the role of the hippocampus in memory function. A central thesis involving work with rats, monkeys, and humans (which has sometimes seemed to proceed independently in 3 separate literatures) is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented that proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in the neocortex that together represent a whole memory. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline dience- phalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experi- mental studies with amnesic patients of fact and event learning, remember- ing and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.
Gave 98 undergraduates a list of 20 common English nouns. Ss were told to inspect each word until a specific episodic memory associated with it came to mind, and to write a few words to identify that memory. After finishing the list, they were asked to go back and to date the episodic memories as accurately as they could. The frequency of memories as a function of their age was log log linear, with the frequency inversely related to the age of memory. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Examined whether lesions of the hippocampus (HIP), entorhinal cortex (EC), or parietal cortex in rats produce retrograde amnesia for spatial 2-choice discriminations in an 8-arm radial maze. In 2 experiments, 37 male rats were trained successively on 2 single-pair discriminations before lesions were performed. After recovery, Ss were tested for retention of the discriminations. Results indicate that the HIP lesions produced a retention deficit that could be interpreted to reflect either a retrograde and/or an anterograde amnesic effect. Ss with HIP lesions were impaired in retention and reacquisition of spatial discriminations in either successive or concurrent testing procedures. Ss with HIP lesions were impaired in learning a new 2-pair concurrent spatial discrimination. Lesions of the EC produced a retention deficit that might be interpreted to reflect a retrograde amnesic effect. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Assessed retrograde amnesia associated with lesions of the hippocampus, amygdala, and overlying allocortex in 8 cynomolgus monkeys (
Macaca fascicularis) trained on 2-choice object discriminations 2–32 wks prior to surgery. Six weeks prior to surgery, Ss were trained on a motor skill task. Three weeks after surgery, nonlesioned controls performed as well on object pairs they had last seen 9 mo earlier as they did on object pairs learned a few weeks earlier. Lesioned Ss performed at or near chance on object pairs from the 5 preoperative periods, indicating a profound memory loss that persisted in retention tests during the following 8 mo. Retention of the preoperatively learned motor skill was excellent in both groups. While learning of new object pairs was impaired after surgery, new motor skills were acquired at a normal rate. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
In a series of radial-arm maze experiments to investigate the behavioral functions of the hippocampal system in rats, both the type of stimulus to be remembered (extramaze stimuli with a constant topological relationship or intramaze stimuli with a changing topological relationship) and the type of memory procedure (working memory procedure or reference memory procedure) were manipulated independently. Results provide no support for spatial or cognitive mapping ideas of hippocampal function; a deficit was found in nonspatial versions of the maze, and a dissociation of performance was found in a spatial version. Thus, the important dimension for predicting the effects of hippocampal damage was the type of memory required and not the type of stimulus to be remembered. Peer commentary by 38 researchers and the author's reply are appended. (7 p ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation. Hippocampus 2001;11:707–714. © 2001 Wiley-Liss, Inc.
The report attempts to delineate certain residual learning capacities of H.M., a young man who became amnesic in 1953 following a bilateral removal in the hippocampal zone. In addition to being able to acquire new motor skills (CORKIN [2]), this patient shows some evidence of perceptual learning. He also achieves some retention of very simple visual and tactual mazes in which the sequence of required turns is short enough to fit into his immediate memory span; even then, the rate of acquisition is extremely slow. These vestigial abilies, which have their occasional parallels in the patient's everyday life, are assessed against the background of his continuing profound amnesia for most on-going events, an amnesia that persists in spite of above-average intelligence and superior performance on many perceptual tasks.
Rats with hippocampal lesions and control animals were tested for spontaneous alternation behavior in a modified T-maze under three different stimulus conditions. When intra-maze stimuli (alley brightness) and spatial direction could be used simultaneously as cues for alternation, both groups alternated at rates significantly higher than chance. However, when intra-maze stimuli were opposed to spatial direction cues, the rats with hippocampal lesions alternated at chance levels while the controls continued to alternate spatial direction. The complexity of the phenomenon of spontaneous alternation itself and the locus and extent of the lesions employed were discussed as possible sources of the discrepancy between the results of this study and others investigating the role of hippocampus in spontaneous alternation behavior.
The case of a 36-year-old man who suffers dense retrograde and anterograde amnesia as a result of closed-head injury that caused extensive damage to his left frontal-parietal and right parieto-occipital lobes is described. Patient K.C. has normal intelligence and relatively well-preserved perceptual, linguistic, short-term memory, and reasoning abilities. He possesses some fragmentary general knowledge about his autobiographical past, but he does not remember a single personal event or happening from any time of his life. He has some preserved expert knowledge related to the work he did for 3 years before the onset of amnesia, although he has no personal recollections from that period. Some features of K.C.'s retrograde amnesia can be interpreted in terms of the distinction between episodic and semantic memory, and in terms of the distinction between episodic and semantic autobiographical knowledge. K.C.'s semantic knowledge, but not his episodic knowledge, showed progressive improvement, or priming, in the course of the investigation.
Eleven alcoholic patients with Korsakoff's disease and 15 control subjects were given three tests of retrograde amnesia. The first consisted of photographs of famous faces from the past, the second was a recall test of famous people and events, and the third was a multiple-choice questionnaire. To determine whether previously reported temporal gradients (ie, preservation of remote events) were related to item difficulty, half of the questions dealt with events of transient fame while half concerned subjects that continued to receive public attention for many years. The findings indicate that alcoholic patients with Korsakoff's disease have a marked retrograde amnesia that is characterized by a steep temporal gradient, and that this gradient is not an artifact due to the difficulty of the questions or the method of testing.
Two experiments are reported in which a stimulus reminder technique was used in an attempt to compensate for the disruptive effects of hippocampal lesions on passive avoidance (PA) conditioning. Groups of hippocampal, cortical and operated control rats were trained to run down an alley for water reward. When the approach response had stabilized, shock was introduced in the goal-box, resulting in increased running times in the control groups and the characteristic PA impairment in the hippocampal group. A recall test was administered 24 hr later but 2 hr before the test, animals were reminded of the previous treatment by being exposed to: (1) shock and related stimuli, (2) related stimuli only, or (3) neutral stimuli. The PA performance of the hippocampus groups in the recall test improved to the level of controls following conditions 1 or 2; there was no effect of condition on Treatment 3. Performance of control groups was virtually unaffected by any of the reminder conditions. The similarities were noted between these results and those of partial cueing studies involving human amnesics with known or suspected damage to the hippocampal system.
A newly designed remote memory test has been used to assess the temporal dimension of prolonged retrograde amnesia. Patients given a course of electroconvulsive treatments for relief of depressive illness exhibited a temporal gradient of retrograde amnesia after five treatments. Memories acquired up to about 3 years before treatment were impaired, but memories acquired 4 to 17 yearss before treatment were not affected. The results suggest that the neural substrate of memory gradually changes with the passage of time after learning and that resistance to amnesic treatment can continue to develop for years.
Patients with anterograde amnesia, including the case H.M. and a group of alcoholic Korsakov cases, were tested for their prompted and unprompted recognition of public figures who had become famous at various points in time from the 1920's to the 1960's. The comparisons between prompted and unprompted recognition for figures from before and after the onsets of the patients' amnesic syndromes were discussed in relation to competing theories of anterograde amnesia. The results were interpreted as not favoring the strong versions of either a faulty-storage or a faulty-retrieval theory.
Five experiments were conducted to compare the contribution of the hippocampal formation and amygdala to mnemonic processes. The performance of rats with damage to the hippocampal formation or amygdala was examined in tests of visual and olfactory non-matching-to-sample with familiar items, cross-modal association, gustatory neophobia, topographical memory, autonomic conditioning to context, and configural discriminations. Neither lesion affects non-matching-to-sample performance. An intact hippocampal formation, but not amygdala, is necessary for cross-modal association between vision and olfaction, topographical memory, conditioning to context, and configural discrimination learning. Amygdala damage disrupted gustatory neophobia and may have impaired learning an association between an auditory cue and food reward.
The present research was concerned with anterograde and retrograde memory for a socially transmitted food preference in rats with lesions to the dorsal hippocampus or dorsomedial thalamus, and operated controls. In Expt. 1, food-preference training was administered postoperatively and memory was tested following various delays. Both lesioned groups acquired the preference normally, but rats with hippocampal lesions displayed a rapid rate of forgetting that indicated significant anterograde amnesia. In Expt. 2, the food preference was acquired at different times preoperatively and retrograde memory was tested postoperatively. Both lesioned groups exhibited loss of memory when training immediately preceded surgery, but only rats with hippocampal lesions displayed a temporally-graded retrograde amnesia. The results confirmed the differential effects of hippocampal and thalamic lesions on memory performance. It was suggested that memory loss following thalamic lesions was related to factors associated with original learning, whereas the pattern of hippocampal amnesia reflected disruption at a later stage in the learning process.