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Objective: Head direction cell and place cell spatially tuned firing is often anchored to salient visual landmarks on the periphery of a recording environment. What is less well understood is whether structural features of an environment, such as orientation of a maze sub‐compartment or a polarizing barrier, can likewise control spatial firing. Method: We recorded from 54 head direction cells in the medial entorhinal cortex and subicular region of male Lister Hooded rats while they explored an apparatus with four parallel or four radially arranged compartments (Experiment 1). In Experiment 2, we recorded from 130 place cells (in Lister‐ and Long‐Evans Hooded rats) and 30 head direction cells with 90° rotations of a cue card and a barrier in a single environment (Experiment 2). Results: We found that head direction cells maintained a similar preferred firing direction across four separate maze compartments even when these faced different directions (Experiment 1). However, in an environment with a single compartment, we observed that both a barrier and a cue card exerted comparable amounts of stimulus control over head direction cells and place cells (Experiment 2). Conclusion: The maintenance of a stable directional orientation across maze compartments suggests that the head direction cell system has the capacity to provide a global directional reference that allows the animal to distinguish otherwise similar maze compartments based on the compartment's orientation. A barrier is, however, capable of controlling spatially tuned firing in an environment in which it is the sole polarizing feature. [ABSTRACT FROM AUTHOR]

• Damage to the head direction circuit produces only modest impairments in spatial behavior. • Head direction cells predict spatial behavior in some tasks, but not others. • New evidence suggests that there are different kinds of head direction cells. • Different head direction cells may underlie different spatial abilities. The head direction cell system is an interconnected set of brain structures containing neurons whose firing is directionally tuned. The robust representation of allocentric direction by head direction cells suggests that they provide a neural compass for the animal. However, evidence linking head direction cells and spatial behavior has been mixed. Whereas damage to the hippocampus yields profound deficits in a range of spatial tasks, lesions to the head direction cell system often yield milder impairments in spatial behavior. In addition, correlational approaches have shown a correspondence between head direction cells and spatial behavior in some tasks, but not others. These mixed effects may be explained in part by a new view of the head direction cell system arising from recent demonstrations of at least two types of head direction cells: 'traditional' cells, and a second class of 'sensory' cells driven by polarising features of an environment. The recognition of different kinds of head direction cells now allows a nuanced assessment of this system's role in guiding navigation. [ABSTRACT FROM AUTHOR]

Hippocampal place cells fire at different rates when a rodent runs through a given location on its way to different destinations. However, it is unclear whether such firing represents the animal's intended destination or the execution of a specific trajectory. To distinguish between these possibilities, Lister Hooded rats (n = 8) were trained to navigate from a start box to three goal locations via four partially overlapping routes. Two of these led to the same goal location. Of the cells that fired on these two routes, 95.8% showed route-dependent firing (firing on only one route), whereas only two cells (4.2%) showed goal-dependent firing (firing similarly on both routes). In addition, route-dependent place cells over-represented the less discriminable routes, and place cells in general over-represented the start location. These results indicate that place cell firing on overlapping routes reflects the animal's route, not its goals, and that this firing may aid spatial discrimination. [ABSTRACT FROM AUTHOR]

The head direction system is composed of neurons found in a number of connected brain areas that fire in a sharply tuned, directional way. The function of this system, however, has not been fully established. To assess this, we devised a novel spatial landmark task, comparable to the paradigms in which stimulus control has been assessed for spatially tuned neurons. The task took place in a large cylinder and required rats to dig in a specific sand cup, from among 16 alternatives, to obtain a food reward. The reinforced cup was in a fixed location relative to a salient landmark, and probe sessions confirmed that the landmark exerted stimulus control over the rats' cup choices. To assess the contribution of the head direction cell system to this memory task, half of the animals received ibotenic acid infusions into the lateral mammillary nuclei (LMN), an essential node in the head direction network, while the other received sham lesions. No differences were observed in performance of this task between the 2 groups. Animals with LMN lesions were impaired, however, in reversal learning on a water maze task. These results suggest that the LMN, and potentially the head direction cell system, are not essential for the use of visual landmarks to guide spatial behavior. [ABSTRACT FROM AUTHOR]

The article discusses the various neuroscience studies using bats on the hippocampal place cells or neurons that fire based on where an animal is located in its environment. Also cited are the presence of said cells in mammalian species like bats, humans, and mice, how the individual place cells in the brain's CA1 fire in multiple, irregularly spaced locations, and the multiscale coding mechanism in bats.

ABSTRACT The discovery of place cells by John O'Keefe in the early 1970s was a breakthrough not just for systems neuroscience, but also for psychology: place fields provided a clear neural substrate for the notion of a cognitive map, a construct devised to explain rat learning and spatial cognition. However, is the robust location-related firing of place cells still best conceptualised as a cognitive map? In this commentary, we reassess this view of hippocampus function in light of subsequent findings on place cells. We argue that as place fields encode local space, and as they are modulated by ongoing behavior, the representation they provide may be more cognitive than map-like. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT The chances of developing psychiatric disorders in adulthood are increased when stress is experienced early in life. In particular, stress experienced in the childhood or 'prepubertal' phase is associated with the later development of disorders such as depression, anxiety, post-traumatic stress disorder, and psychosis. Relatively little is known about the biological basis of this effect, but one hypothesis is that prepubertal stress produces long-lasting changes in brain development, particularly in stress sensitive regions such as the hippocampus, leaving an individual vulnerable to disorders in adulthood. In this study, we used an animal model of prepubertal stress to investigate the hypothesis that prepubertal stress induces alterations in hippocampal function in adulthood. Male and female rats were exposed to a brief, variable prepubertal stress protocol (postnatal days 25-27), and their performance in two distinct hippocampal-dependent tasks (contextual fear and spatial navigation) was compared with controls in adulthood. Prepubertal stress significantly impaired contextual fear responses in males and enhanced performance in spatial navigation in females. These results demonstrate that exposure to a brief period of stress in the prepubertal phase alters hippocampal-dependent behaviors in adulthood in a sex-specific manner. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The postsubiculum is a structure of interest because it projects to the hippocampal formation and contains head direction cells, grid cells, and border cells. The aim of the current experiment was to test whether the postsubiculum is necessary for homing by path integration. Rats were trained on a homing task on a large circular platform. After exhibiting stable homing, one group of animals (n = 6) received ibotenic acid lesions of the postsubiculum, and a second (n = 5) underwent a control surgery. After recovery, animals with postsubiculum lesions homed as accurately as the control animals. Subsequent testing on a delayed alternation T maze task showed that the lesioned animals were significantly worse than the control animals at delays of 5-, 30-, and 60-s. These findings suggest that the postsubiculum is necessary for memory and avoidance of previously visited locations but is not necessary for homing. [ABSTRACT FROM AUTHOR]

The hippocampus is thought to be required for the associative recognition of objects together with the spatial or temporal contexts in which they occur. However, recent data showing that rats with fornix lesions perform as well as controls in an object-place task, while being impaired on an object-place-context task (Eacott and Norman () J Neurosci 24:1948-1953), suggest that not all forms of context-dependent associative recognition depend on the integrity of the hippocampus. To examine the role of the hippocampus in context-dependent recognition directly, the present study tested the effects of large, selective, bilateral hippocampus lesions in rats on performance of a series of spontaneous recognition memory tasks: object recognition, object-place recognition, object-context recognition and object-place-context recognition. Consistent with the effects of fornix lesions, animals with hippocampus lesions were impaired only on the object-place-context task. These data confirm that not all forms of context-dependent associative recognition are mediated by the hippocampus. Subsequent experiments suggested that the object-place task does not require an allocentric representation of space, which could account for the lack of impairment following hippocampus lesions. Importantly, as the object-place-context task has similar spatial requirements, the selective deficit in object-place-context recognition suggests that this task requires hippocampus-dependent neural processes distinct from those required for allocentric spatial memory, or for object memory, object-place memory or object-context memory. Two possibilities are that object, place, and context information converge only in the hippocampus, or that recognition of integrated object-place-context information requires a hippocampus-dependent mode of retrieval, such as recollection. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Detailed memories for unique episodes from an individual's past can be triggered, often effortlessly, when that individual is exposed to a stimulus that was present during the original event. The aim of Kesner et al. (2008) is to understand the neural basis of memory encoding that supports this cued recall of episodic memories. Kesner and colleagues make novel use of an object-place paired-associate task for rats to provide evidence for a critical role of dorsal CA3 in certain aspects of episodic memory encoding. Using one-trial cued recall versions of the task they show that when rats are cued with an object stimulus, they can be trained to revisit the location in which the object appeared previously. Conversely, when rats are cued with a location, they can learn to choose the object with which it was associated. Rats with dorsal CA3 lesions are severely impaired at these tasks. These data are consistent with the theory that the autoassociative network in CA3 supports the rapid formation of novel associations and may allow pattern completion―the phenomenon whereby a subset of the cues present at an encoding event triggers recall of the whole event. Although flexible recall of arbitrary associations is not fully demonstrated, the study contributes 2 novel behavioral tasks to the previously limited repertoire for studying paired associate recall in rats. It also builds on previous data to specify the role of the hippocampal CA3 subregion in cued recall―a critical aspect of episodic memory. [ABSTRACT FROM AUTHOR]

It has been proposed that declarative memories can be dependent on both an episodic and a semantic memory system. While the semantic system deals with factual information devoid of reference to its acquisition, the episodic system, characterized by mental time travel, deals with the unique past experience in which an event took place. Episodic memory is characteristically hippocampus-dependent. Place cells are recorded from the hippocampus of rodents and their firing reflects many of the key characteristics of episodic memory. For example, they encode information about 'what' happens 'where,' as well as temporal information. However, when these features are expressed during an animal's behavior, the neuronal activity could merely be categorizing the present situation and could therefore reflect semantic memory rather than episodic memory. We propose that mental time travel is the key feature of episodic memory and that it should take a form, in the awake animal, similar to the replay of behavioral patterns of activity that has been observed in hippocampus during sleep. Using tasks designed to evoke episodic memory, one should be able to see memory reactivation of behaviorally relevant sequences of activity in the awake animal while recording from hippocampus and other cortical structures. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To examine whether the hippocampus is required for memory for unique experiences independent of their spatial or temporal context, the authors devised a novel task that requires rats to remember odor-reward associations formed within a single training trial. Unlike previous tests of l-trial memory, in this task new associations with otherwise familiar stimuli must be formed, and accurate judgments cannot be based on relative familiarity or recency of the stimuli. The authors show that intact rats performed well on this novel test of event memory. Furthermore, rats with lesions of the hippocampus showed no impairments, even over long retention intervals. These data suggest that the hippocampus is not required for event-specific stimulus-reward associations and that other brain structures mediate this aspect of episodic memory. [ABSTRACT FROM AUTHOR]

Reports data from an rat study which supports the view that the hippocampus has a general role in memory. Activity of hippocampal neurons in rats performing an odor-memory task; Dependence of rats on a non-spatial olfactory memory to feed themselves; Variated experiments; Discovery that cells were more likely to have non-spatial than spatial determinants; Indication that hippocampal neurons are equally available to process spatial and non-spatial data.

Focuses on an experiment which seeks to solve a paradox relating to injuries of the hippocampus region in rats. Explanation of paradox; Details of experiments; Effects of injuries to hippocampus region on memory; Listing of related studies; Possible damage resulting from Postischemic processes.

Examines short and long-term modification of reflex function during learning and metamorphosis in Manduca. Neural mechanisms of behavior; Neural circuit mediating defensive withdrawal reflex on the larval proleg of Manduca; Modification of reflex function; Forms of plasticity.

Presents information about a study that shows that young animals switch between cues more easily than aged animals and also perform better on a spatial learning task. Comparison of hippocampal cognitive maps and spatial behavior in young adult and aged rodents; Reason for the older hippocampal being slower to switch between maps; Experiment that draws a direct linkbetween a particular property of hippocampal place cell firing and spatial performance in both old and young animals.

In this commentary, we highlight a difficulty for metric navigation arising from recent data with grid and place cells: the integration of piecemeal representations of space in environments with repeated boundaries. Put simply, it is unclear how place and grid cells might provide a global representation of distance when their fields appear to represent repeated boundaries within an environment. One implication of this is that the capacity for spatial inferences may be limited. [ABSTRACT FROM PUBLISHER]

A fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham‐lesioned mice (n = 6) following 90° rotations of either distal landmarks or proximal cues in a cue‐ controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham‐lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway. [ABSTRACT FROM AUTHOR]

Hippocampal place cells support spatial cognition and are thought to form the neural substrate of a global "cognitive map." A widely held view is that parts of the hippocampus also underlie the ability to separate patterns or to provide different neural codes for distinct environments. However, a number of studies have shown that in environments composed of multiple, repeating compartments, place cells and other spatially modulated neurons show the same activity in each local area. This repetition of firing fields may reflect pattern completion and may make it difficult for animals to distinguish similar local environments. In this review we 1) highlight some of the navigation difficulties encountered by humans in repetitive environments, 2) summarize literature demonstrating that place and grid cells represent local and not global space, and 3) attempt to explain the origin of these phenomena. We argue that the repetition of firing fields can be a useful tool for understanding the relationship between grid cells in the entorhinal cortex and place cells in the hippocampus, the spatial inputs shared by these cells, and the propagation of spatially related signals through these structures. [ABSTRACT FROM AUTHOR]

Background: Fragile X syndrome (FXS) is a common single gene cause of intellectual disability and autism spectrum disorder. Cognitive inflexibility is one of the hallmarks of FXS with affected individuals showing extreme difficulty adapting to novel or complex situations. To explore the neural correlates of this cognitive inflexibility, we used a rat model of FXS (Fmr1−/y). Methods: We recorded from the CA1 in Fmr1−/y and WT littermates over six 10-min exploration sessions in a novel environment—three sessions per day (ITI 10 min). Our recordings yielded 288 and 246 putative pyramidal cells from 7 WT and 7 Fmr1−/y rats, respectively. Results: On the first day of exploration of a novel environment, the firing rate and spatial tuning of CA1 pyramidal neurons was similar between wild-type (WT) and Fmr1−/y rats. However, while CA1 pyramidal neurons from WT rats showed experience-dependent changes in firing and spatial tuning between the first and second day of exposure to the environment, these changes were decreased or absent in CA1 neurons of Fmr1−/y rats. These findings were consistent with increased excitability of Fmr1−/y CA1 neurons in ex vivo hippocampal slices, which correlated with reduced synaptic inputs from the medial entorhinal cortex. Lastly, activity patterns of CA1 pyramidal neurons were dis-coordinated with respect to hippocampal oscillatory activity in Fmr1−/y rats. Limitations: It is still unclear how the observed circuit function abnormalities give rise to behavioural deficits in Fmr1−/y rats. Future experiments will focus on this connection as well as the contribution of other neuronal cell types in the hippocampal circuit pathophysiology associated with the loss of FMRP. It would also be interesting to see if hippocampal circuit deficits converge with those seen in other rodent models of intellectual disability. Conclusions: In conclusion, we found that hippocampal place cells from Fmr1−/y rats show similar spatial firing properties as those from WT rats but do not show the same experience-dependent increase in spatial specificity or the experience-dependent changes in network coordination. Our findings offer support to a network-level origin of cognitive deficits in FXS. [ABSTRACT FROM AUTHOR]

Background: Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3. Methods: This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3−/y rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3−/y rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM). Results: We observed that, unlike the wildtype, Nlgn3−/y rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3−/y rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3−/y than wildtype rats, indicating the functional impact of the increased cellular excitability. Limitations: Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life. Conclusions: We describe altered fear responses in Nlgn3−/y rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD. [ABSTRACT FROM AUTHOR]

Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders. [ABSTRACT FROM PUBLISHER]

ABSTRACT In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Previous results suggest that directional information from the head direction cell circuit may inform hippocampal place cell firing when an animal is confronted with visually identical environments. To investigate whether such information might also be essential for spatial behavior, we tested adult, male Lister Hooded rats that had received either bilateral lateral mammillary nuclei (LMN) lesions or sham lesions on a four-way, conditional odor-location discrimination in compartments arranged at 60° to one another. We found that significantly fewer rats in the LMN lesion group were able to learn the task compared to the Sham group. We also found that the extent of the behavioral impairment was highly correlated with the degree of tissue loss in the LMN resulting from the lesion. Animals with LMN lesions were also impaired in a nonmatching-to-sample task in a T maze, and the extent of impairment likewise depended on the extent of the lesion. Performance in the odor-location and T -maze tasks was not affected by tissue loss in the medial mammillary nuclei. Together, these results indicate that the LMN, a key node in the head direction circuit, is critical for solving a spatial task that requires a directional discrimination. [ABSTRACT FROM AUTHOR]

Neurons in the retrohippocampal cortices play crucial roles in spatial memory. Many retrohippocampal neurons have firing fields that are selectively active at specific locations, with memory for rewarded locations associated with reorganization of these firing fields. Whether this is the sole strategy for representing spatial memories is unclear. Here, we demonstrate that during a spatial memory task retrohippocampal neurons encode location through ramping activity that extends across segments of a linear track approaching and following a reward, with the rewarded location represented by offsets or switches in the slope of the ramping activity. Ramping representations could be maintained independently of trial outcome and cues marking the reward location, indicating that they result from recall of the track structure. When recorded in an open arena, neurons that generated ramping activity during the spatial memory task were more numerous than grid or border cells, with a majority showing spatial firing that did not meet criteria for classification as grid or border representations. Encoding of rewarded locations through offsets and switches in the slope of ramping activity also emerged in recurrent neural network models trained to solve a similar spatial memory task. Impaired performance of model networks following disruption of outputs from ramping neurons is consistent with this coding strategy supporting navigation to recalled locations of behavioral significance. Our results suggest that encoding of learned spaces by retrohippocampal networks employs both discrete firing fields and continuous ramping representations. We hypothesize that retrohippocampal ramping activity mediates readout of learned models for goal-directed navigation. [Display omitted] • Neurons in the retrohippocampal cortex use ramping activity to encode location • Ramping activity is consistent with recall of learned models of the environment • Neurons with ramping activity are observed more frequently than grid or border cells • Ramping emerges in artificial recurrent neural networks that learn a similar task The retrohippocampal cortices are crucial for spatial memory. Tennant et al. show that neurons in the retrohippocampal cortices represent learned environments through ramping activity profiles. These profiles are distinct from well-studied discrete spatial firing fields and may be well suited to readout learned models of space. [ABSTRACT FROM AUTHOR]

Recent studies have shown that place cells in the hippocampus possess firing fields that repeat in physically similar, parallel environments. These results imply that it should be difficult for animals to distinguish parallel environments at a behavioral level. To test this, we trained rats on a novel odor-location task in an environment with four parallel compartments which had previously been shown to yield place field repetition. A second group of animals was trained on the same task, but with the compartments arranged in different directions, an arrangement we hypothesised would yield less place field repetition. Learning of the odorlocation task in the parallel compartments was significantly impaired relative to learning in the radially arranged compartments. Fewer animals acquired the full discrimination in the parallel compartments compared to those trained in the radial compartments, and the former also required many more sessions to reach criterion compared to the latter. To confirm that the arrangement of compartments yielded differences in place cell repetition, in a separate group of animals we recorded from CA1 place cells in both environments. We found that CA1 place cells exhibited repeated fields across four parallel local compartments, but did not do so when the same compartments were arranged radially. To confirm that the differences in place field repetition across the parallel and radial compartments depended on their angular arrangement, and not incidental differences in access to an extra-maze visual landmark, we repeated the recordings in a second set of rats in the absence of the orientation landmark. We found, once again, that place fields showed repetition in parallel compartments, and did not do so in radially arranged compartments. Thus place field repetition, or lack thereof, in these compartments was not dependent on extra-maze cues. Together, these results imply that place field repetition constrains spatial learning. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood-brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies. [ABSTRACT FROM AUTHOR]

The laterodorsal nucleus (LDN) of the thalamus provides a prominent afferent projection to the postsubiculum (dorsal presubiculum). To characterize synaptic transmission in this pathway, we placed stimulating electrodes in the LDN and recorded fEPSPs elicited in the postsubiculum of urethane-anesthetized rats. LDN stimulation elicited a source-sink dipole between the deep and superficial layers of the postsubiculum, respectively, consistent with anatomical evidence for the termination of thalamic afferents in the superficial layers of the structure, and the existence of deep layer neurons with apical dendrites extending into these layers. Postsubicular fEPSPs were typically 0.5-1.0 mV in amplitude, with a peak latency of approximately 6 ms. Consistent with anatomical observations, the short onset latency of fEPSPs elicited by LDN stimulation, and their ability to follow a 60-Hz train of stimulation, indicate that the projection is monosynaptic. Paired-pulse stimulation revealed pronounced paired-pulse depression that was maximal at 100 ms, suggesting that initial release probabilities are high at LDN-postsubiculum synapses, in common with many neocortical pathways. A conventional tetanus protocol that yields LTP in hippocampal pathways had no effect on postsubicular fEPSPs, but long-term depression could be induced by 60-Hz stimulation. Drug infusion studies revealed that synaptic transmission in the LDN-postsubiculum projection is predominantly AMPA-receptor mediated. Rats were implanted with indwelling infusion cannulae targeting the postsubiculum, and, after a recovery period, were anaesthetized withurethane, and implanted with stimulating and recording electrodes. Infusion of CNQX almost completely abolished postsubicular fEPSPs, whereas D-AP5 had little effect. However, 60-Hz LTD was blocked by D-AP5 infusion, revealing that this form of synaptic plasticity is NMDA-receptor dependent. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Visual landmarks exert stimulus control over spatial behavior and the spatially tuned firing of place, head-direction, and grid cells in the rodent. However, the neural site of convergence for representations of landmarks and representations of space has yet to be identified. A potential site of plasticity underlying associations with landmarks is the postsubiculum. To test this, we blocked glutamatergic transmission in the rat postsubiculum with CNQX, or NMDA receptor-dependent plasticity with D-AP5. These infusions were sufficient to block evoked potentials from the lateral dorsal thalamus and long-term depression following tetanization of this input to the postsubiculum, respectively. In a second experiment, CNQX disrupted the stability of rat hippocampal place cell fields in a familiar environment. In a novel environment, blockade of plasticity with D-AP5 in the postsubiculum did not block the formation of a stable place field map following a 6 h delay. In a final behavioral experiment, postsubicular infusions of both compounds blocked object-location memory in the rat, but did not affect object recognition memory. These results suggest that the postsubiculum is necessary for the recognition of familiar environments, and that NMDA receptor-dependent plasticity in the postsubiculum is required for the formation of new object-place associations that support recognition memory. However, plasticity in the postsubiculum is not necessary for the formation of new spatial maps. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) is a powerful method for exploring emotional and cognitive brain responses in humans. However rodent fMRI has not previously been applied to the analysis of learned behaviour in awake animals, limiting its use as a translational tool. Here we have developed a novel paradigm for studying brain activation in awake rats responding to conditioned stimuli using fMRI. Using this method we show activation of the amygdala and related fear circuitry in response to a fear-conditioned stimulus and demonstrate that the magnitude of fear circuitry activation is increased following early life stress, a rodent model of affective disorders. This technique provides a new translatable method for testing environmental, genetic and pharmacological manipulations on emotional and cognitive processes in awake rodent models. [ABSTRACT FROM AUTHOR]

Myelinated axons have a distinct protein architecture essential for action potential propagation, neuronal communication, and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, contributes to age-related cognitive decline. We sought to determine early alterations in the protein architecture of myelinated axons and potential mechanisms after hypoperfusion. Using a mouse model of hypoperfusion, we assessed changes in proteins critical to the maintenance of paranodes, nodes of Ranvier, axon- glial integrity, axons, and myelin by confocal laser scanning microscopy. As early as 3 d after hypoperfusion, the paranodal septate-like junctions were damaged. This was marked by a progressive reduction of paranodal Neurofascin signal and a loss of septate-like junctions. Concurrent with paranodal disruption, there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. Disruption of axon- glial integrity was also determined after hypoperfusion by changes in the spatial distribution of myelin-associated glycoprotein staining. These nodal/paranodal changes were more pronounced after 1 month of hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Neurofascin 186 were unchanged and there were no overt changes in axonal and myelin integrity with hypoperfusion. A microarray analysis of white matter samples indicated that there were significant alterations in 129 genes. Subsequent analysis indicated alterations in biological pathways, including inflammatory responses, cytokinecytokine receptor interactions, blood vessel development, and cell proliferation processes. Our results demonstrate that hypoperfusion leads to a rapid disruption of key proteins critical to the stability of the axon- glial connection that is mediated by a diversity of molecular events. [ABSTRACT FROM AUTHOR]

Abstract: The hippocampus is hypothesised to be critical for episodic memory in humans and episodic-like memory in animals. Human data regarding the roles of the various subregional networks within the hippocampus is difficult to obtain. In this article we examine the current rodent literature on episodic-like memory and associative recognition and review the roles of the hippocampal subregions in these behavioural tasks. We focus on the large amount of recent data reporting roles for CA3 and CA1 in allocentric spatial and temporal associative memory respectively. Our own recent data are then presented detailing critical roles for CA3 and CA1 in an associative recognition task which does not require allocentric spatial or temporal processing. These data support more generic roles for CA3 and CA1 in episodic-like memory, based on anatomical and theoretical literature on hippocampal function. We also present a novel analysis of our data in which we suggest that the encoding of object, place and context information is unaffected by lesions of the hippocampus and therefore infer that it may be the storage or retrieval phase of this associative memory which is critically dependent on hippocampal function. In conclusion however, more specific anatomically and temporally controlled methods are needed to fully define the role of hippocampal subregions in episodic-like memory. [Copyright &y& Elsevier]

Path integration, the ability to maintain a representation of location and direction on the basis of internal cues, is thought to be important for navigation and the learning of spatial relationships. Representations of location and direction in the brain, such as head direction cells, grid cells, and place cells in the limbic system, are thought to underlie navigation by path integration. While this idea is generally consistent with lesion studies, the relationship between such neural activity and behavior has not been studied on a task where animals demonstrably use a path integration strategy. Here we report the development of such a task in rats: by slowly rotating rats before their return to a trial-unique home base, we could show subjects relied on internal cues only to navigate. To illustrate how this task can be combined with recording, we show examples of simultaneously recorded head direction cells in which neural activity is closely related to rats' homing direction. These results support the notion that rats can navigate by path integration, that this ability depends on head direction cells, and suggest a convenient behavioral paradigm for investigating the neural basis of navigation. [ABSTRACT FROM AUTHOR]

In a continuous T-maze spatial alternation task, CA1 place cells fire differentially on the stem of the maze as rats are performing left- and right-turn trials (Wood et al. () Neuron 27:623-633). This context-dependent hippocampal activity provides a potential mechanism by which animals could solve the alternation task, as it provides a cue that could prime the appropriate goal choice. The aim of this study was to examine the relationship between context-dependent hippocampal activity and spatial alternation behavior. We report that rats with complete lesions of the hippocampus learn and perform the spatial alternation task as well as controls if there is no delay between trials, suggesting that the observed context-dependent hippocampal activity does not mediate alternation behavior in this task. However lesioned rats are significantly impaired when delays of 2 or 10 s are interposed. Recording experiments reveal that context-dependent hippocampal activity occurs in both the delay and no-delay versions of the task, but that in the delay version it occurs during the delay period, and not on the stem of the maze. These data are consistent with a role for context-dependent hippocampal activity in delayed spatial alternation, but suggest that, according to specific task demands and memory load, the activity may be generated by different mechanisms and/or in different brain structures. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation. [ABSTRACT FROM AUTHOR]

Abstract: Studies examining the effects of hippocampal lesions on object recognition memory in rats have produced conflicting results. The present study investigated how methodological differences and lesion size may have contributed to these discrepancies. In Experiment 1 we compared rats with complete, partial (septal) and sham hippocampal lesions on a spontaneous object recognition task, using a protocol previously reported to result in deficits following large hippocampal lesions . Rats with complete and partial hippocampal lesions were unimpaired, suggesting the hippocampus is not required for object recognition memory. However, rats with partial lesions showed relatively poor performance raising the possibility that floor effects masked a deficit on this group. In Experiment 2, we used a second spontaneous object recognition protocol similar to that used by the two other studies that have reported deficits following hippocampal lesions . Rats with complete hippocampal lesions were significantly impaired, whereas rats with partial lesions were unimpaired. However, the complete lesion group showed less object exploration during the sample phase. Thus, the apparent recognition memory deficit in Experiment 2 may be attributable to differential encoding. Together, these findings suggest that the hippocampus is not required for intact spontaneous object recognition memory. These findings suggest that levels of object exploration during the sample phase may be a critical issue, and raise the possibility that previous reports of object recognition deficits may be due to differences in object exploration rather than deficits in object recognition per se. [Copyright &y& Elsevier]

Summary A central tenet of systems neuroscience is that the mammalian hippocampus provides a cognitive map of the environment. This view is supported by the finding of place cells, neurons whose firing is tuned to specific locations in an animal’s environment, within this brain region. Recent work, however, has shown that these cells repeat their firing fields across visually identical maze compartments [ 1, 2 ]. This repetition is not observed if these compartments face different directions, suggesting that place cells use a directional input to differentiate otherwise similar local environments [ 3, 4 ]. A clear candidate for this input is the head direction cell system. To test this, we disrupted the head direction cell system by lesioning the lateral mammillary nuclei and then recorded place cells as rats explored multiple, connected compartments, oriented in the same or in different directions. As shown previously, we found that place cells in control animals exhibited repeated fields in compartments arranged in parallel, but not in compartments facing different directions. In contrast, the place cells of animals with lesions of the head direction cell system exhibited repeating fields in both conditions. Thus, directional information provided by the head direction cell system appears essential for the angular disambiguation by place cells of visually identical compartments. [ABSTRACT FROM AUTHOR]