Biomedical subjects

Inah Lee

Publications and source records attributed to Inah Lee.

14 recordsLinked to original sources

PubMed2006

Gradual translocation of spatial correlates of neuronal firing in the hippocampus toward prospective reward locations.

In a continuous T-maze alternation task, CA1 complex-spike neurons in the hippocampus differentially fire as the rat traverses overlapping segments of the maze (i.e., the stem) repeatedly via alternate routes. The temporal dynamics of this phenomenon were further investigated in the current study. Rats learned the alternation task from the first day of acquisition and the differential firing pattern in the stem was observed accordingly. More importantly, we report a phenomenon in which spatial correlates of CA1 neuronal ensembles gradually changed from their original firing locations, shifting toward prospective goal locations in the continuous T-maze alternation task. The relative locations of simultaneously recorded firing fields, however, were preserved within the ensemble spatial representation during this shifting. The within-session shifts in preferred firing locations in the absence of any changes in the environment suggest that certain cognitive factors can significantly alter the location-bound coding scheme of hippocampal neurons.

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PubMed2006

Hippocampal place cells: parallel input streams, subregional processing, and implications for episodic memory.

The hippocampus is thought to be involved in episodic memory in humans. Place cells of the rat hippocampus offer a potentially important model system to understand episodic memory. However, the difficulties in determining whether rats have episodic memory are profound. Progress can be made by considering the hippocampus as a computational device that presumably performs similar transformations on its inputs in both rats and in humans. Understanding the input/output transformations of rat place cells can thus inform research on the computational basis of human episodic memory. Two examples of different transformations in the CA3 and CA1 regions are presented. In one example, CA3 place fields are shown to maintain a greater degree of population coherence than CA1 place fields after a rearrangement of the salient landmarks in an environment, in agreement with computational models of CA3 as an autoassociative network. In the second example, CA3 place field appears to store information about the spatiotemporal sequences of place fields, starting with the first exposure to a cue-altered environment, whereas CA1 place fields store this information only on a temporary basis. Finally, recordings of hippocampal afferents from the lateral and medial entorhinal cortex (EC) suggest that these two regions convey fundamentally different representations to the hippocampus, with spatial information conveyed by the medial EC and nonspatial information conveyed by the lateral EC. The dentate gyrus and CA3 regions may create configural object+place (or item+context) representations that provide the spatiotemporal context of an episodic memory.

Action Potentials↗

PubMed2005

Patterns of hippocampal cell loss based on subregional lesions of the hippocampus.

It is widely accepted that the hippocampus plays an essential role in memory. Furthermore, studies have suggested that subregions within the hippocampus contribute differentially to specific behavioral components of memory. These studies typically rely on lesions produced by localized injections of neurotoxins (e.g., ibotenic acid or colchicine) into targeted subregions of the hippocampus. In the present study, the specificity of ibotenic acid lesions into areas CA1 and CA3 and colchicine lesions into the dorsal dentate gyrus (DG) was tested. Specifically, the effects of lesions within the dorsal hippocampus, the ventral hippocampus, and areas outside the hippocampus (e.g., lateral septum and entorhinal cortex) were evaluated using Fluoro-Jade, a histofluorescent stain for degenerating neurons. The results show that cell loss is relatively uniform after ibotenic acid injections into areas CA1 and CA3 and variable after colchicine injections into DG. CA1 and CA3 lesions appeared mostly localized to those relative subregions, and DG lesions appeared highly localized to the DG. Using these lesion procedures, little cell loss was apparent in the ventral hippocampus, and no cell loss was apparent in the entorhinal cortex. It is suggested that the lesion procedures described in this study produce relatively selective lesions of neurons within specific subregions of the hippocampus and should be useful for studies examining possible differential contributions of hippocampal subregions to memory processes.

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PubMed2005

Major dissociation between medial and lateral entorhinal input to dorsal hippocampus.

Hippocampal place cells are a model system of how the brain constructs cognitive representations and of how these representations support complex behavior, learning, and memory. There is, however, a lack of detailed knowledge about the properties of hippocampal afferents. We recorded multiple single units from the hippocampus and the medial and lateral entorhinal areas of behaving rats. Although many medial entorhinal neurons had highly specific place fields, lateral entorhinal neurons displayed weak spatial specificity. This finding demonstrates a fundamental dissociation between the information conveyed to the hippocampus by its major input streams, with spatial information represented by the medial and nonspatial information represented by the lateral entorhinal cortex.

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PubMed2005

Disruption of delayed memory for a sequence of spatial locations following CA1- or CA3-lesions of the dorsal hippocampus.

Axon-sparing neurotoxic lesions of CA1 or CA3 were produced in the dorsal hippocampus to test dissociative lesion effects on spatial working memory for sequential items. Rats were required to remember four different sections sequentially presented on a newly devised maze (i.e., Tulum maze) during a study phase. Each section was cued by a unique object that was specifically associated with each location within the section during the study phase. Following a 15-s delay and during the test phase, rats were required to revisit the location within a section randomly chosen among the previously visited sections in the absence of the cued object. Both CA1 and CA3 lesions similarly disrupted accurate relocation of a previously visited place. However, differential effects of the CA1 and CA3 lesions were observed in serial position curves. CA3-lesions disrupted performance for the first three serial positions, but did not disrupt performance for the last serial position (recency). In contrast, CA1-lesions disrupted performance for all serial positions. The results suggest that temporal separation of spatial memory may depend on the conjoint function of CA1 and CA3 of the hippocampus with a disruption of a spatial pattern completion process following CA3 lesions and a disruption of a temporal pattern separation process following a CA1 lesion.

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PubMed2005

The role of hippocampal subregions in detecting spatial novelty.

Previous literature suggests that the hippocampus subserves processes associated with the encoding of novel information. To investigate the role of different subregions of the hippocampus, the authors made neurotoxic lesions in different subregions of the dorsal hippocampus (i.e., CA1, dentate gyrus [DG], or CA3) of rats, followed by tests using a spontaneous object exploration paradigm. All lesion groups explored normally an object newly introduced in a familiar location. However, when some of the familiar objects were moved to novel locations, both DG and CA3 lesion groups were severely impaired in reexploring the displaced objects, whereas the CA1 lesion group was only mildly impaired in reexploration. The results suggest that the DG-CA3 network is essential in detecting novelty for spatial, but not for individual object, information.

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PubMed2004

Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3.

The hippocampus, a critical brain structure for navigation, context-dependent learning and episodic memory, is composed of anatomically heterogeneous subregions. These regions differ in their anatomical inputs as well as in their internal circuitry. A major feature of the CA3 region is its recurrent collateral circuitry, by which the CA3 pyramidal cells make excitatory synaptic contacts on each other. In contrast, pyramidal cells in the CA1 region are not extensively interconnected. Although these differences have inspired numerous theoretical models of differential processing capacities of these two regions, there have been few reports of robust differences in the firing properties of CA1 and CA3 neurons in behaving animals. The most extensively studied of these properties is the spatially selective firing of hippocampal 'place cells'. Here we report that in a dynamically changing environment, in which familiar landmarks on the behavioural track and along the wall are rotated relative to each other, the population representation of the environment is more coherent between the original and cue-altered environments in CA3 than in CA1. These results demonstrate a functional heterogeneity between the place cells of CA3 and CA1 at the level of neural population representations.

Action Potentials↗

PubMed2004

A double dissociation between hippocampal subfields: differential time course of CA3 and CA1 place cells for processing changed environments.

Computational theories have suggested different functions for the hippocampal subfields (e.g., CA1 and CA3) in memory. However, it has been difficult to find dissociations relevant to these hypothesized functions in investigations of the hippocampal correlates of space ("place fields") in freely behaving animals. The current study demonstrates a double dissociation between the shifts in the center of mass (COM) of the place fields that were simultaneously recorded in CA1 and CA3 when familiar cue configurations were dynamically changed over days. The COM of CA3 place fields shifted backward in the first experience of the cue-changed environment, whereas the COM of CA1 place fields did not display the backward shift until the next day. These results support the hypothesis that CA3 plays a key role in the rapid formation of representations of new spatiotemporal sequences, whereas CA1 may be more important for comparing currently experienced sequence information with stored sequences in the CA3 network.

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PubMed2004

Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus.

The hippocampus is an essential neural structure for spatial memory. Computational models suggest that the CA3 subregion of the hippocampus plays an essential role in encoding and retrieval of spatial memory. The perforant path (PPCA3) and dentate gyrus (DG)-mediated mossy fibers (MFs) compose major afferent inputs into CA3. A possible functional dissociation between these afferent inputs was attempted using a simple navigation test (i.e., the modified Hebb-Williams maze). Behavioral testing was combined with electrolytic lesions of PPCA3 or neurotoxic lesions of the DG, to eliminate each afferent input into CA3. Lesions in either afferent input into CA3 affected learning of an effective navigational path on the maze. The contributions of the two CA3 afferent inputs, however, were different regarding encoding and retrieval of memory measured based on indices operationally defined for the behavioral paradigm (i.e., encoding, the number of errors reduced within a day; retrieval, the number of errors reduced between days). The DG-lesioned animals exhibited deficits regarding the encoding index, but not the retrieval index, whereas the PPCA3-lesioned rats displayed deficits regarding the retrieval index, but not the encoding index. The results suggest that the two major afferent inputs of CA3 may contribute differentially to encoding and retrieval of spatial memory.

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PubMed2004

Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear-conditioning.

The hippocampus is an essential neural structure in developing contextual memory in a situation in which rapid development of associative learning should occur. We tested a subregion-specific contribution in the hippocampus to memory acquisition and retrieval, using the contextual fear-conditioning paradigm. The current results suggest that all three subregions (i.e., CA3, CA1, and dentate gyrus) of the hippocampus contribute to rapid acquisition of contextual memory in the initial phase of acquisition. The involvement of CA3 seems to be important at the earliest stage of acquisition, presumably for developing instant representation of a context. The role of CA3, however, was minimal in retrieving contextual memory after a long time period (i.e., 24 h), whereas the other subregions (i.e., CA1 and dentate gyrus) were critically involved. The results indicate time-dependent differential contributions of the hippocampal subregions to memory acquisition and retrieval in contextual fear-conditioning.

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PubMed2004

A behavioral assessment of hippocampal function based on a subregional analysis.

The purpose of this review is to determine whether specific subregions (dentate gyrus [DG], CA3, and CA1) of the hippocampus provide unique contributions to specific processes associated with intrinsic information processing exemplified by novelty detection, encoding, pattern separation, pattern association, pattern completion, retrieval, short-term memory and intermediate-term memory. Based on anatomical neural network organization, electrophysiology of cellular activity, lesions, early gene activation, and computational modeling, it can be shown that there exists extensive cooperation among the three subregions of the hippocampus, but there also exists reliable specificity of function for each of the subregions of the hippocampus. The primary process supported by the DG subregion of the hippocampus can be characterized by orthogonalization of sensory inputs to create a metric spatial representation. Furthermore the DG participates in conjunction with CA3 in supporting spatial pattern separation. The CA3 subregion of the hippocampus supports processes associated with spatial pattern association, spatial pattern completion, novelty detection, and short-term memory. The CA1 subregion of the hippocampus supports processes associated with temporal pattern association, temporal pattern completion, and intermediate-term memory. Furthermore, the CA3 in conjunction with CA1 supports temporal pattern separation. All the above-mentioned processes are assumed to reflect intrinsic processing of information within the hippocampus. The diversity of functions associated with the different subregions of the hippocampus suggests that one should not treat the hippocampus as a single entity, but rather that one should concentrate on elucidating further the functions of both dorsal and ventral subregions of the hippocampus and pathways that directly connect each of the subregions as well as their connections with the entorhinal cortex.

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PubMed2003

Time-dependent relationship between the dorsal hippocampus and the prefrontal cortex in spatial memory.

The prefrontal cortex and the dorsal hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.

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PubMed2003

Differential roles of dorsal hippocampal subregions in spatial working memory with short versus intermediate delay.

In order to determine the role of subregions of the hippocampus in spatial working memory, this study combined selective neurotoxic lesions of the hippocampal subregions with a simple delayed nonmatching-to-place task on a radial maze in rats. Lesions of the dentate gyrus or the CA3, but not the CA1, subregion of the hippocampus induced a deficit in the acquisition of the task with short-term delays (i.e., 10 sec) and impaired performance of the task in a novel environment. All subregional lesions produced sustained impairment in performing the task with intermediate-term delays (i.e., 5 min) when rats were tested in a familiar environment. The results suggest a dynamic interaction among the dorsal hippocampal subregions in processing spatial working memory, with the time window (i.e., delay) of a task recognized as an essential controlling factor.

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PubMed2002

Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory.

N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity in the mammalian hippocampus is essential for learning and memory. Although computational models and anatomical studies have emphasized functional differences among hippocampal subregions, subregional specificity of NMDA receptor function is largely unknown. Here we present evidence that NMDA receptors in CA3 are required in a situation in which spatial representation needs to be reorganized, whereas the NMDA receptors in CA1 and/or the dentate gyrus are more involved in acquiring memory that needs to be retrieved after a delay period exceeding a short-term range. Our data, with data from CA1-specific knockout mice, suggest the possibility of heterogeneous mnemonic function of NMDA receptors in different subregions of the hippocampus.

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