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There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

Hippocampal place cells are spatially tuned neurons that serve as elements of a 'cognitive map' in the mammalian brain.sup.1. 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 landmarks.sup.2,3 and measuring the distance and direction that the animal has travelled from previously occupied locations.sup.4-7. 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 accumulates.sup.8,9. Models of hippocampal place cells and entorhinal grid cells based on path integration treat the path-integration gain as a constant.sup.9-14, but behavioural evidence in humans suggests that the gain is modifiable.sup.15. 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 system.sup.4,8,16-19, 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., Author(s): Ravikrishnan P. Jayakumar [sup.1] , Manu S. Madhav [sup.2] , Francesco Savelli [sup.2] , Hugh T. Blair [sup.3] , Noah J. Cowan [sup.1] [sup.4] , James J. Knierim [sup.2] [...]

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]

Subfields of the hippocampus display differential dynamics in processing a spatial environment, especially when changes are introduced to the environment. Specifically, when familiar cues in the environment are spatially rearranged, place cells in the CA3 subfield tend to rotate with a particular set of cues (e.g., proximal cues), maintaining a coherent spatial representation. Place cells in CA1, in contrast, display discordant behaviors (e.g., rotating with different sets of cues or remapping) in the same condition. In addition, on average, CA3 place cells shift their firing locations (measured by the center of mass, or COM) backward over time when the animal encounters the changed environment for the first time, but not after that first experience. However, CA1 displays an opposite pattern, in which place cells exhibit the backward COM-shift only from the second day of experience, but not on the first day. Here, we examined the relationship between the environment-representing behavior (i.e., rotation vs. remapping) and the COM-shift of place fields in CA1 and CA3. Both in CA1 and CA3, the backward (as well as forward) COM-shift phenomena occurred regardless of the rotating versus remapping of the place cell. The differential, daily time course of the onset/offset of backward COM-shift in the cue-altered environment in CA1 and CA3 (on day 1 in CA1 and from day 2 onward in CA3) stems from different population dynamics between the subfields. The results suggest that heterogeneous, complex plasticity mechanisms underlie the environment-representating behavior (i.e., rotate/remap) and the COM-shifting behavior of the place cell.

Place cells of the rat hippocampus are a dominant model system for understanding the role of the hippocampus in learning and memory at the level of single-unit and neural ensemble responses. A complete understanding of the information processing and computations performed by the hippocampus requires detailed knowledge about the properties of the representations that are present in hippocampal afferents and efferents in order to decipher the transformations that occur to these representations in the hippocampal circuitry. Neural recordings in behaving rats have revealed a number of brain areas that contain place-related firing properties in the parahippocampal regions and in other brain regions that are thought to interact with the hippocampus in certain behavioral tasks. Although investigators have just begun to scratch the surface in terms of understanding these properties, differences in the precise nature of the spatial firing between the hippocampus and these other regions promise to reveal important clues regarding the exact role of the hippocampus in learning and memory and the nature of its interactions with other brain systems to support adaptive behavior.

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.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., Author(s): Francesco Savelli, James J. KnierimAuthor Affiliations:AI mimics brain codes for navigation Deep-learning networks can be taught how to process inputs to achieve a particular output -- for instance, learning [...]

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]