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The hippocampal dentate gyrus (DG) is thought to orthogonalize inputs from the entorhinal cortex (pattern separation) and relay this information to the CA3 region. In turn, attractor dynamics in CA3 perform a pattern completion or error correction operation before sending its output to CA1. In a mouse model of congenital hypoplasia of the DG, a deficiency in the Wntless (Wls) gene, specifically in cells expressing Gfap-Cre, which targets neuronal progenitors, led to an almost total absence of dentate granule cells and modestly impaired performance in spatial tasks. Here, we investigated the physiological consequences of granule cell loss in these mice by conducting in vivo calcium imaging from CA1 principal cells during behavior. The spatial selectivity of these cells was preserved without the DG. On a linear track, place fields in mutant mice were more likely to be near track terminals and to encode the distance from the start point in each running direction. In an open box, CA1 cells in mutant mice exhibited reductions in the percentage of place cells, in spatial information, and in place field stability. The reduction in place field stability across repeated exposures to the same environment resulted in a reduction in the differential representations of two different contexts in mutant mice compared to wild-type mice. These results suggest that DG helps to stabilize CA1 spatial representations, especially in 2-D environments, and that the lack of stability across similar environments may play a key role in the deficits of animals with DG dysfunction in discriminating different environments. [ABSTRACT FROM AUTHOR]

Vector coding is a major mechanism by which neural systems represent an animal's location in both global and local, item-based reference frames. Landmark vector cells (LVCs) in the hippocampus complement classic place cells by encoding vector relationships between the organism and specific landmarks. How these place- and vector-coding properties interact is not known. We recorded place cells and LVCs using calcium imaging of the CA1 region of freely moving rats during cue-card rotation studies. Place fields rotated around the center of the platform to follow the cue rotation, whereas the fields of simultaneously recorded LVCs rotated by the same amount around the nearby landmarks. Some neurons demonstrated conjunctive coding of both classic place field properties and LVC properties. These results demonstrate that CA1 neurons employ a common directional input, presumably provided by the head direction cell system, to encode animals' locations in both world-centered and landmark-centered reference frames. How directional information is integrated into classic place coding and landmark vector coding within the hippocampus remain not fully understood. Here authors show that, both place cells and landmark vector cells (LVCs) receive identical directional inputs, yet the firing fields of place cells and LVCs rotated by similar degrees relative to the center of the environment and relative to the nearby landmark, respectively. [ABSTRACT FROM AUTHOR]

The hippocampal formation is vulnerable to the process of normal aging. In humans, the extent of this age‐related deterioration varies among individuals. Long–Evans rats replicate these individual differences as they age, and therefore they serve as a valuable model system to study aging in the absence of neurodegenerative diseases. In the Morris water maze, aged memory‐unimpaired (AU) rats navigate to remembered goal locations as effectively as young rats and demonstrate minimal alterations in physiological markers of synaptic plasticity, whereas aged memory‐impaired (AI) rats show impairments in both spatial navigation skills and cellular and molecular markers of plasticity. The present study investigates whether another cognitive domain is affected similarly to navigation in aged Long–Evans rats. We tested the ability of young, AU, and AI animals to recognize novel object‐place‐context (OPC) configurations and found that performance on the novel OPC recognition paradigm was significantly correlated with performance on the Morris water maze. In the first OPC test, young and AU rats, but not AI rats, successfully recognized and preferentially explored objects in novel OPC configurations. In a second test with new OPC configurations, all age groups showed similar OPC associative recognition memory. The results demonstrated similarities in the behavioral expression of associative, episodic‐like memory between young and AU rats and revealed age‐related, individual differences in functional decline in both navigation and episodic‐like memory abilities. [ABSTRACT FROM AUTHOR]

Entorhinal cortex is the major gateway between the neocortex and the hippocampus and thus plays an essential role in subserving episodic memory and spatial navigation. It can be divided into the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), which are commonly theorized to be critical for spatial (context) and non‐spatial (content) inputs, respectively. Consistent with this theory, LEC neurons are found to carry little information about allocentric self‐location, even in cue‐rich environments, but they exhibit egocentric spatial information about external items in the environment. The superficial and deep layers of LEC are believed to mediate the input to and output from the hippocampus, respectively. As earlier studies mainly examined the spatial firing properties of superficial‐layer LEC neurons, here we characterized the deep‐layer LEC neurons and made direct comparisons with their superficial counterparts in single unit recordings from behaving rats. Because deep‐layer LEC cells received inputs from hippocampal regions, which have strong selectivity for self‐location, we hypothesized that deep‐layer LEC neurons would be more informative about allocentric position than superficial‐layer LEC neurons. We found that deep‐layer LEC cells showed only slightly more allocentric spatial information and higher spatial consistency than superficial‐layer LEC cells. Egocentric coding properties were comparable between these two subregions. In addition, LEC neurons demonstrated preferential firing at lower speeds, as well as at the boundary or corners of the environment. These results suggest that allocentric spatial outputs from the hippocampus are transformed in deep‐layer LEC into the egocentric coding dimensions of LEC, rather than maintaining the allocentric spatial tuning of the CA1 place fields. [ABSTRACT FROM AUTHOR]

Age-related memory deficits are correlated with neural hyperactivity in the CA3 region of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from young and aged, male, Long–Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite, decreasing trend, in that CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared with young (Y) rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus (DG), the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote abnormal, bistable representations under certain conditions. [ABSTRACT FROM AUTHOR]

The complementary processes of pattern completion and pattern separation are thought to be essential for successful memory storage and recall. The dentate gyrus (DG) and proximal CA3 (pCA3) regions have been implicated in pattern separation, in part through extracellular recording studies of these areas. However, the DG contains two types of excitatory cells: granule cells of the granule layer and mossy cells of the hilus. Little is known about the firing properties of mossy cells in freely moving animals, and it is unclear how their activity may contribute to the mnemonic functions of the hippocampus. Furthermore, tetrodes in the dentate granule layer and pCA3 pyramidal layer can also record mossy cells, thus introducing ambiguity into the identification of cell types recorded. Using a random forests classifier, we classified cells recorded in DG (Neunuebel and Knierim, 2014) and pCA3 (Lee et al., 2015) of 16 male rats and separately examined the responses of granule cells, mossy cells, and pCA3 pyramidal cells in a local/global cue mismatch task. All three cell types displayed low correlations between the population representations of the rat's position in the standard and cue-mismatch sessions. These results suggest that all three excitatory cell types within the DG/pCA3 circuit may act as a single functional unit to support pattern separation. [ABSTRACT FROM AUTHOR]

Hippocampal place cells are spatially tuned neurons that serve as elements of a 'cognitive map' in the mammalian brain1. To detect the animal's location, place cells are thought to rely upon two interacting mechanisms: sensing the position of the animal relative to familiar landmarks2,3 and measuring the distance and direction that the animal has travelled from previously occupied locations4-7. The latter mechanism—known as path integration—requires a finely tuned gain factor that relates the animal's self-movement to the updating of position on the internal cognitive map, as well as external landmarks to correct the positional error that accumulates8,9. Models of hippocampal place cells and entorhinal grid cells based on path integration treat the path-integration gain as a constant9-14, but behavioural evidence in humans suggests that the gain is modifiable15. Here we show, using physiological evidence from rat hippocampal place cells, that the path-integration gain is a highly plastic variable that can be altered by persistent conflict between self-motion cues and feedback from external landmarks. In an augmented-reality system, visual landmarks were moved in proportion to the movement of a rat on a circular track, creating continuous conflict with path integration. Sustained exposure to this cue conflict resulted in predictable and prolonged recalibration of the path-integration gain, as estimated from the place cells after the landmarks were turned off. We propose that this rapid plasticity keeps the positional update in register with the movement of the rat in the external world over behavioural timescales. These results also demonstrate that visual landmarks not only provide a signal to correct cumulative error in the path-integration system4,8,16-19, but also rapidly fine-tune the integration computation itself. Evidence from hippocampal place cells shows that path-integration gain, previously thought to be a constant factor in the computation of location, is flexible and can be rapidly fine-tuned. [ABSTRACT FROM AUTHOR]

Path integration is a straightforward concept with varied connotations that are important to different disciplines concerned with navigation, such as ethology, cognitive science, robotics and neuroscience. In studying the hippocampal formation, it is fruitful to think of path integration as a computation that transforms a sense of motion into a sense of location, continuously integrated with landmark perception. Here, we review experimental evidence that path integration is intimately involved in fundamental properties of place cells and other spatial cells that are thought to support a cognitive abstraction of space in this brain system. We discuss hypotheses about the anatomical and computational origin of path integration in the wellcharacterized circuits of the rodent limbic system. We highlight how computational frameworks for map-building in robotics and cognitive science alike suggest an essential role for path integration in the creation of a new map in unfamiliar territory, and how this very role can help us make sense of differences in neurophysiological data from novel versus familiar and small versus large environments. Similar computational principles could be at work when the hippocampus builds certain non-spatial representations, such as time intervals or trajectories defined in a sensory stimulus space. [ABSTRACT FROM AUTHOR]

The encoding of time and its binding to events are crucial for episodic memory, but how these processes are carried out in hippocampal-entorhinal circuits is unclear. Here we show in freely foraging rats that temporal information is robustly encoded across time scales from seconds to hours within the overall population state of the lateral entorhinal cortex. Similarly pronounced encoding of time was not present in the medial entorhinal cortex or in hippocampal areas CA3-CA1. When animals’ experiences were constrained by behavioural tasks to become similar across repeated trials, the encoding of temporal flow across trials was reduced, whereas the encoding of time relative to the start of trials was improved. The findings suggest that populations of lateral entorhinal cortex neurons represent time inherently through the encoding of experience. This representation of episodic time may be integrated with spatial inputs from the medial entorhinal cortex in the hippocampus, allowing the hippocampus to store a unified representation of what, where and when. Temporal information that is useful for episodic memory is encoded across a wide range of timescales in the lateral entorhinal cortex, arising inherently from its representation of ongoing experience. [ABSTRACT FROM AUTHOR]

Hippocampal place cells exhibit spatially modulated firing, or place fields, which can remap to encode changes in the environment or other variables. Unique among hippocampal subregions, the dentate gyrus (DG) has two excitatory populations of place cells, granule cells and mossy cells, which are among the least and most active spatially modulated cells in the hippocampus, respectively. Previous studies of remapping in the DG have drawn different conclusions about whether granule cells exhibit global remapping and contribute to the encoding of context specificity. By recording granule cells and mossy cells as mice foraged in different environments, we found that by most measures, both granule cells and mossy cells remapped robustly but through different mechanisms that are consistent with firing properties of each cell type. Our results resolve the ambiguity surrounding remapping in the DG and suggest that most spatially modulated granule cells contribute to orthogonal representations of distinct spatial contexts. [Display omitted] • Machine-learning-based classifier for granule cell and mossy cell recordings • Granule cells and mossy cells remapped to a similar degree overall • Sparsely firing granule cells often remapped through different active populations • Highly active mossy cells often remapped through spatially decorrelated place fields Kim et al. show cell-type-specific properties of spatial firing in the dentate gyrus by recording from single cells as mice freely explored distinct environments. These findings support the role of both granule cells and mossy cells in global remapping and orthogonalization (pattern separation) of spatial representations in dentate gyrus. [ABSTRACT FROM AUTHOR]

ABSTRACT A longstanding debate in hippocampus research has revolved around how to reconcile spatial mapping functions of the hippocampus with the global amnesia produced by hippocampal damage in humans. Is the hippocampus primarily a cognitive map used to support spatial learning, or does it support more general types of learning necessary for declarative memory? In recent years, a general consensus has emerged that the hippocampus receives both spatial and nonspatial inputs from the entorhinal cortex. The hippocampus creates representations of experience in a particular spatial and temporal context. This process allows the individual components of experience to be stored in such a way that they can be retrieved together as a conscious recollection. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, somatic hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, somatic hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. [ABSTRACT FROM AUTHOR]

The hippocampus is thought to have a critical role in episodic memory by incorporating the sensory input of an experience onto a spatial framework embodied by place cells. Although the formation and stability of place fields requires exploration, the interaction between discrete exploratory behaviors and the specific, immediate and persistent modifications of neural representations required by episodic memory has not been established. We recorded place cells in rats and found that increased neural activity during exploratory head-scanning behaviors predicted the formation and potentiation of place fields on the next pass through that location, regardless of environmental familiarity and across multiple testing days. These results strongly suggest that, during the attentive behaviors that punctuate exploration, place cell activity mediates the one-trial encoding of ongoing experiences necessary for episodic memory. [ABSTRACT FROM AUTHOR]

The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between 'where' versus 'what' needs revision. We propose a refinement of this model, which is more complex than the simple spatial-non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience. [ABSTRACT FROM AUTHOR]

Manipulation of spatial reference frames is a common experimental tool to investigate the nature of hippocampal information coding and to investigate high-order processes, such as cognitive coordination. However, it is unknown how the hippocampus afférents represent the local and global reference frames of an environment. To address these issues, single units were recorded in freely moving rats with multi-tetrode arrays targeting the superficial layers of the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two primary cortical inputs to the hippocampus. Rats ran clockwise laps around a circular track partitioned into quadrants covered by different textures (the local reference frame). The track was centered in a circular environment with distinct landmarks on the walls (the global reference frame). Here we demonstrate a novel dissociation between MEC and LEC in that the global frame controlled the MEC representation and the local frame controlled the LEC representation when the reference frames were rotated in equal, but opposite, directions. Consideration of the functional anatomy of the hippocampal circuit and popular models of attractor dynamics in CA3 suggests a mechanistic explanation of previous data showing a dissociation between the CA3 and CAI regions in their responses to this local-global conflict. Furthermore, these results are consistent with a model of the LEC providing the hippocampus with the external sensory content of an experience and the MEC providing the spatial context, which combine to form conjunctive codes in the hippocampus that form the basis of episodic memory. [ABSTRACT FROM AUTHOR]

The hippocampus is thought to represent nonspatial information in the context of spatial information. An animal can derive both spatial information as well as nonspatial information from the objects (landmarks) it encounters as it moves around in an environment. In this article, correlates of both object-derived spatial as well as nonspatial information in the hippocampus of rats foraging in the presence of objects are demonstrated. A new form of CA1 place cells, called landmark-vector cells, that encode spatial locations as a vector relationship to local landmarks is described. Such landmark vector relationships can be dynamically encoded. Of the 26 CA1 neurons that developed new fields in the course of a day's recording sessions, in eight cases, the new fields were located at a similar distance and direction from a landmark as the initial field was located relative to a different landmark. In addition, object-location memory in the hippocampus is also described. When objects were removed from an environment or moved to new locations, a small number of neurons in CA1 and CA3 increased firing at the locations where the objects used to be. In some neurons, this increase occurred only in one location, indicating object + place conjunctive memory; in other neurons, the increase in firing was seen at multiple locations where an object used to be. Taken together, these results demonstrate that the spatially restricted firing of hippocampal neurons encode multiple types of information regarding the relationship between an animal's location and the location of objects in its environment. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The medial temporal lobe (MTL) is involved in mnemonic processing. The perirhinal cortex (PRC) plays a role in object recognition memory, while the hippocampus is required for certain forms of spatial memory and episodic memory. The lateral entorhinal cortex (LEC) receives direct projections from PRC and is one of the two major cortical inputs to the hippocampus. The transformations that occur between PRC and LEC neural representations are not well understood. Here, we show that PRC and LEC had similarly high proportions of neurons with object-related activity (PRC 52/94; LEC 72/153), as expected from their locations in the 'what' pathway into the hippocampus. However, LEC unit activity showed more spatial stability than PRC unit activity. A minority of LEC neurons showed stable spatial firing fields away from objects; these firing fields strongly resembled hippocampal place fields. None of the PRC neurons showed this place-like firing. None of the PRC or LEC neurons demonstrated the high firing rates associated with interneurons in hippocampus or medial entorhinal cortex, further dissociating this information processing stream from the path-integration based, movement-related processing of the medial entorhinal cortex and hippocampus. These results provide evidence for nonspatial information processing in the PRC-LEC pathway, as well as showing a functional dissociation between PRC and LEC, with more purely nonspatial representations in PRC and combined spatial-nonspatial representations in LEC. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Attractor networks are a popular computational construct used to model different brain systems. These networks allow elegant computations that are thought to represent a number of aspects of brain function. Although there is good reason to believe that the brain displays attractor dynamics, it has proven difficult to test experimentally whether any particular attractor architecture resides in any particular brain circuit. We review models and experimental evidence for three systems in the rat brain that are presumed to be components of the rat's navigational and memory system. Head-direction cells have been modeled as a ring attractor, grid cells as a plane attractor, and place cells both as a plane attractor and as a point attractor. Whereas the models have proven to be extremely useful conceptual tools, the experimental evidence in their favor, although intriguing, is still mostly circumstantial. [ABSTRACT FROM AUTHOR]

Insight into the processing dynamics and other neurophysiological properties of different hippocampal subfields is critically important for understanding hippocampal function. In this study, we compared shifts in the center of mass (COM) of CA3 and CA1 place fields in a familiar and completely novel environment. Place fields in CA1 and CA3 were simultaneously recorded as rats ran along a closed loop track in a familiar room followed by a session in a completely novel room. This process was repeated each day over a 4-day period. CA3 place fields shifted backward (opposite to the direction of motion of the rat) only in novel environments. This backward shift gradually diminished across days, as the novel environment became more familiar with repeated exposures. Conversely, CA1 place fields shifted backward across all days in both familiar and novel environments. Prior studies demonstrated that CA1 place fields on average do not exhibit a backward shift during the first exposure to an environment in which the familiar cues are rearranged into a novel configuration, although CA3 place fields showed a strong backward shift. Under the completely novel conditions of the present study, no dissociation was observed between CA3 and CA1 during the first novel session (although a strong dissociation was observed in the familiar sessions and the later novel sessions). In summary, this is the first study to use simultaneous recordings in CA1 and CA3 to compare place field COM shift and other associated properties in truly novel and familiar environments. This study further demonstrates functional differentiation between CA1 and CA3 as the plasticity of CA1 place fields is affected differently by exposure to a completely novel environment in comparison to an altered, familiar environment, whereas the plasticity of CA3 place fields is affected similarly during both types of environmental novelty. [ABSTRACT FROM AUTHOR]

The dentate gyrus (DG) occupies a key position in information flow through the hippocampus. Its principal cell, the granule cell, has spatially selective place fields. However, the behavioral correlates of cells located in the hilus of the rat dentate gyrus are unknown. We report here that cells below the granule layer show spatially selective firing that consists of multiple subfields. Other cells recorded from the DG had single place fields. Compared with cells with multiple fields, cells with single fields fired at lower rates during sleep were less bursty, and were more likely to be recorded simultaneously with large populations of neurons that were active during sleep and silent during behavior. We propose that cells with single fields are likely to be mature granule cells that use sparse encoding to potentially disambiguate input patterns. Furthermore, we hypothesize that cells with multiple fields might be cells of the hilus or newborn granule cells. These data are the first demonstration, based on physiological criteria, that single- and multiple-field cells constitute at least two distinct cell classes in the DG. Because of the heterogeneity of firing correlates and cell types in the DG, understanding which cell types correspond to which firing patterns, and how these correlates change with behavioral state and between different environments, are critical questions for testing long-standing computational theories that theDGperforms a pattern separation function using a very sparse coding strategy. [ABSTRACT FROM AUTHOR]

The hippocampus is a brain region that is critical for spatial learning, context-dependent memory, and episodic memory. It receives major inputs from the medial entorhinal cortex (MEC) and the lateral EC (LEC). MEC neurons show much greater spatial firing than LEC neurons in a recording chamber with a single, salient landmark. The MEC cells are thought to derive their spatial tuning through path integration, which permits spatially selective firing in such a cue-deprived environment. In accordance with theories that postulate two spatial mapping systems that provide input to the hippocampus-an internal, path-integration system and an external, landmark-based system-it was possible that LEC neurons can also convey a spatial signal, but that the signal requires multiple landmarks to define locations, rather than movement integration. To test this hypothesis, neurons from the MEC and LEC were recorded as rats foraged for food in cue-rich environments. In both environments, LEC neurons showed little spatial specificity, whereas many MEC neurons showed a robust spatial signal. These data strongly support the notion that the MEC and LEC convey fundamentally different types of information to the hippocampus, in terms of their spatial firing characteristics, under various environmental and behavioral conditions. © 2010 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article discusses the neural representation of frames of reference and their function in spatial navigation. It mentions the use of navigation tasks, such as Morris water task, in behavioral test for hippocampus-dependent spatial learning and memory. It states the behavior of animals in such task is controlled by a local-apparatus frame of reference than distal cues. The significance of navigational tasks in studies of neurobiological mechanisms underlying performance is mentioned.

The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network. [ABSTRACT FROM AUTHOR]

The medial entorhinal cortex (MEC) is thought to create and update a dynamical representation of the animal's spatial location. Most suggestive of this process are grid cells, whose firing locations occur periodically in space. Prior studies in small environments were ambiguous as to whether all spatially modulated cells in MEC were variants of grid cells or whether a subset resembled classic place cells of the hippocampus. Recordings from the dorsal and ventral MEC were performed as four rats foraged in a small square box centered inside a larger one. After 6 min, without removing the rat from the enclosure, the walls of the small box were quickly removed, leaving the rat free to continue foraging in the whole area enclosed by the larger box. The rate-responses of most recorded cells (70 out of 93 cells, including 15 of 16 putative interneurons) were considered spatially modulated based on information-theoretic analysis. A number of cells that resembled classic hippocampal place cells in the small box were revealed to be grid cells in the larger box. In contrast, other cells that fired along the boundaries or corners of the small box did not show grid-cell firing in the large box, but instead fired along the corresponding locations of the large box. Remapping of the spatial response in the area corresponding to the small box after the removal of its walls was prominent in most spatially modulated cells. These results show that manipulation of local boundaries can exert a powerful influence on the spatial firing patterns of MEC cells even when the manipulations leave global cues unchanged and allow uninterrupted, self-motion-based localization. Further, they suggest the presence of landmark-related information in MEC, which might prevent cumulative drift of the spatial representation or might reset it to a previously learned configuration in a familiar environment. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Anatomical and physiological evidence suggests that hippocampal place cells derive their spatial firing properties from the medial entorhinal cortex (MEC) and other parahippocampal areas that send spatial and directional input to the MEC. MEC neurons fire in a precise, geometric pattern, forming a hexagonal grid that tessellates the surface of environments. Similar to place cells and head direction cells, the orientation of grid cell firing patterns can be controlled by visual landmarks, but the cells maintain their firing patterns even in the dark. Place cells and head direction cells can also completely decouple from external landmarks in the light, but it is not known whether the MEC and parahippocampal regions exhibit similar properties or are more explicitly tied to external landmarks. We recorded neurons in the MEC, parasubiculum, and CA1 and head direction cells of the anterior thalamus as the rat's internal direction sense was pitted against a salient visual landmark by slowly rotating the rat in a covered bucket while counter-rotating the visual cue. In different sessions, spatial firing rate maps and head direction tuning curves either rotated their preferred firing locations/directions by the same amount as the bucket rotation or maintained their preferences in the external laboratory framework. In few cases, the firing preferences rotated with the cue card. When cells from different regions were recorded simultaneously, the dominant response in one area almost always matched the response of the other areas. Although dominant responses were consistent throughout the recording regions, CA1 ensembles exhibited a greater degree of response heterogeneity than other regions, which nearly all exhibited internally consistent responses. Thus, the parahippocampal and MEC input to the hippocampus can be controlled by the animal's internal direction sense (presumably reflected in the firing of head direction cells) and become completely decoupled from external sensory input, yet maintain internal coherence with each other and in general with the place cell system of the hippocampus. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Place cells of the hippocampal formation encode a spatial representation of the environment, and the orientation of this representation is apparently governed by the head direction cell system. The representation of a well explored environment by CA1 place cells can be split when there is conflicting information from salient proximal and distal cues, because some place fields rotate to follow the distal cues, whereas others rotate to follow the proximal cues (Knierim, 2002a). In contrast, the CA3 representation is more coherent than CA1, because the place fields in CA3 tend to rotate in the same direction (Lee et al., 2004). The present study tests whether the head direction cell network produces a split representation or remains coherent under these conditions by simultaneously recording both CA1 place cells and head direction cells from the thalamus. In agreement with previous studies, split representations of the environment were observed in ensembles of CA1 place cells in ∼75% of the mismatch sessions, in which some fields followed the counterclockwise rotation of proximal cues and other fields followed the clockwise rotation of distal cues. However, of 225 recording sessions, there was not a single instance of the head direction cell ensembles revealing a split representation of head direction. Instead, in most of the mismatch sessions, the head direction cell tuning curves rotated as an ensemble clockwise (94%) and in a few sessions rotated counterclockwise (6%). The findings support the notion that the head direction cells may be part of an attractor network bound more strongly to distal landmarks than proximal landmarks, even under conditions in which the CA1 place representation loses its coherence. [ABSTRACT FROM AUTHOR]

Hippocampal place cells are selectively active when a rat occupies restricted locations in an environment, and head direction cells fire selectively when the rat’s head is pointed in a particular direction in allocentric space. Both place cells and head direction cells are usually coupled, and they are controlled by a complex interaction between external landmarks and idiothetic cues. Most studies have investigated this interaction by rotating the landmarks in the environment. In contrast, a recent study translated the apparatus relative to the landmarks in an environment and found that most place cells maintained the same preferred location on the apparatus regardless of the location of the apparatus in the room. Because head direction cells are insensitive to the rat’s location in an environment, the distal landmarks may influence the place field firing locations primarily by controlling the bearing of the head direction cell system. To address this question, ensembles of CA1 place cells and head direction cells of the anterior thalamus were recorded simultaneously, as a rectangular or circular track was moved to different locations in a room with distinct visual landmarks. Most place cells maintained their firing fields relative to the track when the track was translated, and head direction cells maintained the same preferred firing direction. When the distal landmarks were rotated around the track, the firing fields of place cells and the preferred directions of head direction cells rotated with the cues. These results suggest that the precise firing locations of place cells are controlled by an interaction between local and idiothetic cues, and the orientation of the CA1 ensemble representation relative to the distal landmarks may be controlled indirectly by the distal landmarks’ influence over the bearing of the head direction cell system. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hippocampal neurons are selectively active when a rat occupies restricted locations in an environment. These place cells derive their specificity from a multitude of sources, including idiothetic cues and sensory input derived from both distal and local landmarks. Most experiments have attempted to dissociate the relative strengths and roles played by these sources by rotating one set against the other. Few studies have addressed the effects of relative translation of the local cue set versus salient distal landmarks. To address this question, ensembles of place cells were recorded as a rectangular or circular track was moved to different locations in a room with controlled visual landmarks. Place cells primarily maintained their firing fields relative to the track (i.e., occupying new locations relative to the distal landmarks), even though the track could occupy completely nonoverlapping regions of the room. When the distal landmarks were rotated around the circular track, however, the place fields rotated with the landmarks, demonstrating that the cues were perceptible to the rat. These results suggest that, under these conditions, the spatial tuning of place cells may derive from an interaction between local and idiothetic cues, which define the precise firing locations of the cells and the relationships between them, and distal landmarks, which set the orientation of the ensemble representation relative to the external environment. Hippocampus 2003;13:604-617. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

An artificial-intelligence technique called deep learning has now been used to model spatial navigation. The system develops a representation of space similar to that of the grid cells found in the mammalian brain. [ABSTRACT FROM AUTHOR]

In a surface-dwelling animal like the rat, experimental strategies for investigating the hippocampal correlates of three-dimensional space appear inevitably complicated by the interplay of global versus local reference frames. We discuss the impact of the resulting confounds on present and future empirical analysis of the “bicoded map” hypothesis by Jeffery and colleagues. [ABSTRACT FROM PUBLISHER]

The article presents a study on brain regions that process information in vertical and horizontal axes producing anisotropy in the representation of three-dimensional outer space conducted by Hayman and colleagues in the U.S. It notes that the findings of the study reveal that the three-dimensional spatial encoding was found in the hippocampus cells and grid cells of the medial entorhinal cortex (MEC). These cells have potential involvement in the three-dimensional representation of the space.

‘Place’ cells of the hippocampus and ‘head-direction’ (HD) cells of the thalamus and limbic cortex derive their spatial and directional specificity from a combination of idiothetic (self-motion) cues and external landmarks, which normally reinforce each other to generate a robust neural code for location and direction. In weightlessness, however, three-dimensional navigation can cause the idiothetic and landmark cues to conflict. Nonetheless, neural recordings on the space shuttle demonstrated that the hippocampus can create a robust spatial code for three orthogonal surfaces in the weightless environment of space flight. [ABSTRACT FROM AUTHOR]