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The hippocampus (HPC) and retrosplenial cortex (RSC) are key components of the brain's memory and navigation systems. Lesions of either region produce profound deficits in spatial cognition and HPC neurons exhibit well‐known spatial firing patterns (place fields). Recent studies have also identified an array of navigation‐related firing patterns in the RSC. However, there has been little work comparing the response properties and information coding mechanisms of these two brain regions. In the present study, we examined the firing patterns of HPC and RSC neurons in two tasks which are commonly used to study spatial cognition in rodents, open field foraging with an environmental context manipulation and continuous T‐maze alternation. We found striking similarities in the kinds of spatial and contextual information encoded by these two brain regions. Neurons in both regions carried information about the rat's current spatial location, trajectories and goal locations, and both regions reliably differentiated the contexts. However, we also found several key differences. For example, information about head direction was a prominent component of RSC representations but was only weakly encoded in the HPC. The two regions also used different coding schemes, even when they encoded the same kind of information. As expected, the HPC employed a sparse coding scheme characterized by compact, high contrast place fields, and information about spatial location was the dominant component of HPC representations. RSC firing patterns were more consistent with a distributed coding scheme. Instead of compact place fields, RSC neurons exhibited broad, but reliable, spatial and directional tuning, and they typically carried information about multiple navigational variables. The observed similarities highlight the closely related functions of the HPC and RSC, whereas the differences in information types and coding schemes suggest that these two regions likely make somewhat different contributions to spatial cognition. [ABSTRACT FROM AUTHOR]

The proximal and distal segments of CA1 are thought to perform distinct computations. Neurons in proximal CA1 are reciprocally connected with the medial entorhinal cortex (MEC) and exhibit precise spatial firing. In contrast, cells in distal CA1 communicate with the lateral entorhinal cortex (LEC), exhibit more diffuse spatial firing and are affected by the presence of objects in the environment. To determine if these segments make unique contributions to memory retrieval, we examined cellular activity along the proximodistal axis of CA1 using transgenic reporter mice. Neurons tagged during context learning in proximal CA1 were more likely to be reactivated during testing than those in distal CA1. This was true following context fear conditioning and after exposure to a novel environment. Reactivation was also higher in brain regions connected to proximal CA1 (MEC, distal CA3) than those connected to the distal segment (LEC, proximal CA3). To examine contributions to memory retrieval, we performed neurotoxic lesions of proximal or distal CA1 after training. Lesions of the proximal segment significantly impaired memory retrieval while damage to distal CA1 had no effect. These data suggest that context memories are retrieved by a hippocampal microcircuit that involves the proximal but not distal segment of CA1. © 2016 Wiley Periodicals, Inc.

Previous studies across species have established that the aging process adversely affects certain memory-related brain regions earlier than others. Behavioral tasks targeted at the function of vulnerable regions can provide noninvasive methods for assessing the integrity of particular components of memory throughout the lifespan. The present study modified a previous task designed to separately but concurrently test detailed memory for object identity and spatial location. Memory for objects or items is thought to rely on perirhinal and lateral entorhinal cortices, among the first targets of Alzheimer's related neurodegeneration. In line with prior work, we split an aged adult sample into "impaired" and "unimpaired" groups on the basis of a standardized word-learning task. The "impaired" group showed widespread difficulty with memory discrimination, whereas the "unimpaired" group showed difficulty with object, but not spatial memory discrimination. These findings support the hypothesized greater age-related impacts on memory for objects or items in older adults, perhaps even with healthy aging. © 2015 Wiley Periodicals, Inc.

Watermaze tests of place learning and memory in rodents and corresponding reverse‐translated human paradigms in real or virtual environments are key tools to study hippocampal function. In common variants, the animal or human participant has to find a hidden goal that remains in the same place over many trials, allowing for incremental learning of the place with reference to distal cues surrounding the circular, featureless maze. Although the hippocampus is involved in incremental place learning, rodent studies have shown that the delayed‐matching‐to‐place (DMP) watermaze test is a more sensitive assay of hippocampal function. On the DMP test, the goal location changes every four trials, requiring the rapid updating of place memory. Here, we developed a virtual DMP test reverse‐translated from the rat watermaze DMP paradigm. In two replications, participants showed 1‐trial place learning, evidenced by marked latency and path length savings between Trials 1 and 2 to the same goal location, and by search preference for the vicinity of the goal when Trial 2 was run as probe trial (during which the goal was removed). The performance was remarkably similar to rats' performance on the watermaze DMP test. In both replications, male participants showed greater savings and search preferences compared to female participants. Male participants also showed better mental rotation performance, although mental rotation scores did not consistently correlate with DMP performance measures, pointing to distinct neurocognitive mechanisms. The remarkable similarity between rodent and human DMP performance suggests similar underlying neuro‐psychological mechanisms, including hippocampus dependence. The new virtual DMP test may, therefore, provide a sensitive tool to probe human hippocampal function. [ABSTRACT FROM AUTHOR]

Although the hippocampus experiences age-related anatomical and functional deterioration, the effects of aging vary across hippocampal-dependent cognitive processes. In particular, whether or not the hippocampus is known to be required for a spatial memory process is not an accurate predictor on its own of whether aging will affect performance. Therefore, the primary objective of this study was to compare the effects of healthy aging on a test of spatial pattern separation and a test of spatial relational processing, which are two aspects of spatial memory that uniquely emphasize the use of multiple hippocampal-dependent processes. Spatial pattern separation supports spatial memory by preserving unique representations for distinct locations. Spatial relational processing forms relational representations of objects to locations or between objects and other objects in space. To test our primary objective, 30 young (18-30 years; 21F) and 30 older participants (60-80 years; 21F) all completed a spatial pattern separation task and a task designed to require spatial relational processing through spatial reconstruction. To ensure aging effects were not due to inadequate time to develop optimal strategies or become comfortable with the testing devices, a subset of participants had extended practice across three sessions on each task. Results showed that older adults performed more poorly than young on the spatial reconstruction task that emphasized the use of spatial relational processing, and that age effects persisted even after controlling for pattern separation performance. Further, older adults performed more poorly on spatial reconstruction than young adults even after three testing sessions each separated by 7-10 days, suggesting effects of aging are resistant to extended practice and likely reflect genuine decline in hippocampal memory abilities. [ABSTRACT FROM AUTHOR]

ABSTRACT Human navigation studies show that landmarks are used for orientation, whereas objects contribute to the contextual representation of an environment. What constitutes a landmark? Classic rodent studies show that hippocampal place fields are controlled by distal, polarizing cues. Place fields, however, are also influenced by local cues. One difficulty in examining mechanisms by which distal and local cues influence the activity of hippocampal cells is that distant cues are necessarily processed visually, whereas local cues are generally multimodal. Here, we compared the effects of 90° rotations under different cue conditions in which cues were restricted to the visual modality. Three two-dimensional visual cue conditions were presented in a square open field: a large vertical cue on one wall, a large floor cue in a corner abutting two walls, and a smaller complex floor cue in a corner adjacent to two walls. We show that rotations of large distal cues, whether on the wall or floor, were equally effective in controlling place fields. Rotations of the smaller floor cues were significantly more likely to result in remapping, whether or not animals were also exposed to the distal polarizing cues. Responses of distal and local cues were affected differently by extended experience. Our data provide evidence that hippocampal place cell responses to visual cues are influenced by perspective, salience of the cue, and prior experience. The hippocampus processes visual cues either as stable landmarks useful for orientation and navigation or as nonstationary objects or features of the local environment available for associative learning or binding items in context. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT As first demonstrated in the patient H.M., the hippocampus is critically involved in forming episodic memories, the recall of 'what' happened 'where' and 'when.' In rodents, the clearest functional correlate of hippocampal primary neurons is the place field: a cell fires predominantly when the animal is in a specific part of the environment, typically defined relative to the available visuospatial cues. However, rodents have relatively poor visual acuity. Furthermore, they are highly adept at navigating in total darkness. This raises the question of how other sensory modalities might contribute to a hippocampal representation of an environment. Rodents have a highly developed olfactory system, suggesting that cues such as odor trails may be important. To test this, we familiarized mice to a visually cued environment over a number of days while maintaining odor cues. During familiarization, self-generated odor cues unique to each animal were collected by re-using absorbent paperboard flooring from one session to the next. Visual and odor cues were then put in conflict by counter-rotating the recording arena and the flooring. Perhaps surprisingly, place fields seemed to follow the visual cue rotation exclusively, raising the question of whether olfactory cues have any influence at all on a hippocampal spatial representation. However, subsequent removal of the familiar, self-generated odor cues severely disrupted both long-term stability and rotation to visual cues in a novel environment. Our data suggest that odor cues, in the absence of additional rule learning, do not provide a discriminative spatial signal that anchors place fields. Such cues do, however, become integral to the context over time and exert a powerful influence on the stability of its hippocampal representation. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT There is ample evidence from human and animal models that sleep contributes to the consolidation of newly learned information. The precise role of sleep for integrating information into interconnected memory representations is less well understood. Building on prior findings that following sleep (as compared to wakefulness) people are better able to draw inferences across learned associations in a simple hierarchy, we ask how sleep helps consolidate relationships in a more complex representational space. We taught 60 subjects spatial relationships between pairs of buildings, which (unknown to participants) formed a two-dimensional grid. Critically, participants were only taught a subset of the many possible spatial relations, which allowed them to potentially infer the remainder. After a 12 h period that either did or did not include a normal period of sleep, participants returned to the lab. We examined the quality of each participant's map of the two-dimensional space, and their knowledge of relative distances between buildings. After 12 h with sleep, subjects could more accurately map the full space than subjects who experienced only wakefulness. The incorporation of untaught, but inferable, associations was particularly improved. We further found that participants' distance judgment performance related to self-reported navigational style, but only after sleep. These findings demonstrate that consolidation over a night of sleep begins to integrate relations into an interconnected complex representation, in a way that supports spatial relational inference. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The hippocampus is involved in encoding and integrating contextual information. Recently, it has been suggested that the dorsal dentate gyrus (dDG) hippocampal subregion may mediate the formation of contextual representations of the spatial environment through a conjunctive encoding process whereby incoming multimodal information is integrated into a single higher-order representation. Despite anatomical evidence in support of this claim, behavioral evidence is limited. Therefore, a contextual associative learning paradigm was used to determine whether the dDG supports the formation of integrated contextual representations. Male Long-Evans rats were randomly assigned as controls or to receive bilateral intracranial infusions of colchicine into the dDG. Following recovery from surgery, each rat was tested on an appetitive task that required animals to form an association between a cue (odor) and a context to receive a food reward. Each rat received 10 trials per day and was tested for 10 consecutive days. Upon completion of testing, animals were tested on an additional two-choice olfactory and contextual discrimination task. The testing order was counterbalanced across animals. Results showed that control animals successfully acquired the contextual associative learning task for olfactory stimuli as indicated by improved performance across the 10 testing days. In contrast, animals with dDG lesions were impaired in the ability to acquire the odor-context associations. Results from follow-up odor and context discrimination tests indicated that both groups acquired the discriminations at similar rates. Therefore, it is unlikely that deficits in performance on the contextual associative learning task were due to an inability to discriminate between odors or contexts. The present findings provide further support for DG involvement in the formation of conjunctive contextual representations. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cover legend: This cover image is based on the Research Article. A new human delayed‐matching‐to‐place test in a virtual environment reverse‐translated from the rodent watermaze paradigm: characterization of performance measures and sex differences, by Matthew G. Buckley and Tobias Bast, DOI: 10.1002/hipo.22992. [ABSTRACT FROM AUTHOR]