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Showing papers on "Spatial memory published in 2018"


Journal ArticleDOI
09 Nov 2018-Science
TL;DR: It is argued that spatial-processing principles in the hippocampalentorhinal region provide a geometric code to map information domains of cognitive spaces for high-level cognition and discuss recent evidence for this proposal.
Abstract: The hippocampal formation has long been suggested to underlie both memory formation and spatial navigation. We discuss how neural mechanisms identified in spatial navigation research operate across information domains to support a wide spectrum of cognitive functions. In our framework, place and grid cell population codes provide a representational format to map variable dimensions of cognitive spaces. This highly dynamic mapping system enables rapid reorganization of codes through remapping between orthogonal representations across behavioral contexts, yielding a multitude of stable cognitive spaces at different resolutions and hierarchical levels. Action sequences result in trajectories through cognitive space, which can be simulated via sequential coding in the hippocampus. In this way, the spatial representational format of the hippocampal formation has the capacity to support flexible cognition and behavior.

360 citations


Journal ArticleDOI
TL;DR: Support is found for the involvement of replay in disparate processes, including the maintenance of hippocampal memories and decision making, and it is proposed that the function of replay changes dynamically according to task demands placed on an organism and its current level of arousal.

240 citations


Journal ArticleDOI
TL;DR: This work provides the first evidence for separable scales of representation along the human hippocampal anteroposterior axis by showing greater similarity among voxel time courses and higher temporal autocorrelation in anterior hippocampus (aHPC) relative to posterior hippocampus (pHPC), the human homologs of ventral and dorsal rodent hippocampus.

175 citations


Journal ArticleDOI
TL;DR: It is shown that sustained voltages in human EEG recordings contain fine-grained information about the orientation of an object being held in memory, consistent with a memory storage signal.
Abstract: In human scalp EEG recordings, both sustained potentials and alpha-band oscillations are present during the delay period of working memory tasks and may therefore reflect the representation of information in working memory. However, these signals may instead reflect support mechanisms rather than the actual contents of memory. In particular, alpha-band oscillations have been tightly tied to spatial attention and may not reflect location-independent memory representations per se. To determine how sustained and oscillating EEG signals are related to attention and working memory, we attempted to decode which of 16 orientations was being held in working memory by human observers (both women and men). We found that sustained EEG activity could be used to decode the remembered orientation of a stimulus, even when the orientation of the stimulus varied independently of its location. Alpha-band oscillations also carried clear information about the location of the stimulus, but they provided little or no information about orientation independently of location. Thus, sustained potentials contain information about the object properties being maintained in working memory, consistent with previous evidence of a tight link between these potentials and working memory capacity. In contrast, alpha-band oscillations primarily carry location information, consistent with their link to spatial attention.SIGNIFICANCE STATEMENT Working memory plays a key role in cognition, and working memory is impaired in several neurological and psychiatric disorders. Previous research has suggested that human scalp EEG recordings contain signals that reflect the neural representation of information in working memory. However, to conclude that a neural signal actually represents the object being remembered, it is necessary to show that the signal contains fine-grained information about that object. Here, we show that sustained voltages in human EEG recordings contain fine-grained information about the orientation of an object being held in memory, consistent with a memory storage signal.

168 citations


Journal ArticleDOI
TL;DR: It is argued that space and time serve as a primary scaffold to break up experiences into specific contexts, and to organize multimodal input that is to be associated within a context.
Abstract: In recent years, the field has reached an impasse between models suggesting that the hippocampus is fundamentally involved in spatial processing and models suggesting that the hippocampus automatically encodes all dimensions of experience in the service of memory. Here, we consider key conceptual issues that have impeded progress in our understanding of hippocampal function, and we review findings that establish the scope and limits of hippocampal involvement in navigation and memory. We argue that space and time serve as a primary scaffold to break up experiences into specific contexts, and to organize multimodal input that is to be associated within a context. However, the hippocampus is clearly capable of incorporating additional dimensions into the scaffold if they are determined to be relevant in the event-defined context. Conceiving of the hippocampal representation as constrained by immediate task demands-yet preferring axes that involve space and time-helps to reconcile an otherwise disparate set of findings on the core function of the hippocampus.

162 citations


Journal ArticleDOI
TL;DR: fMRI activity in human entorhinal cortex is modulated by eye-movement direction with 60° periodicity, implicating a grid cell-like code in mapping visual space and suggesting a role for entorHinal grid coding in cognition beyond spatial navigation.
Abstract: Entorhinal grid cells map the local environment, but their involvement beyond spatial navigation remains elusive. We examined human functional MRI responses during a highly controlled visual tracking task and show that entorhinal cortex exhibited a sixfold rotationally symmetric signal encoding gaze direction. Our results provide evidence for a grid-like entorhinal code for visual space and suggest a more general role of the entorhinal grid system in coding information along continuous dimensions.

153 citations


Journal ArticleDOI
TL;DR: It is suggested that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition, with oscillations in the left increasing when successfully learning object–location pairs and in the right during spatial navigation.
Abstract: The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1–3-Hz “low theta” band increases when viewing subsequently remembered object–location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

124 citations


Journal ArticleDOI
21 Nov 2018-Neuron
TL;DR: It is found that inhibiting SOM, but not PV, interneurons during the encoding phase of the task impaired working memory accuracy, suggesting that interneuron dysfunction may contribute to cognitive deficits associated with schizophrenia by disrupting long-range synchrony between the HPC and PFC.

117 citations


Journal ArticleDOI
TL;DR: The current state of the art of the division of labour within this complex ‘navigation system’ is reviewed, with special focus on how subcortical cholinergic inputs may regulate various aspects of spatial learning, memory and navigation.
Abstract: Spatial learning, including encoding and retrieval of spatial memories as well as holding spatial information in working memory generally serving navigation under a broad range of circumstances, relies on a network of structures. While central to this network are medial temporal lobe structures with a widely appreciated crucial function of the hippocampus, neocortical areas such as the posterior parietal cortex and the retrosplenial cortex also play essential roles. Since the hippocampus receives its main subcortical input from the medial septum of the basal forebrain (BF) cholinergic system, it is not surprising that the potential role of the septo-hippocampal pathway in spatial navigation has been investigated in many studies. Much less is known of the involvement in spatial cognition of the parallel projection system linking the posterior BF with neocortical areas. Here we review the current state of the art of the division of labour within this complex 'navigation system', with special focus on how subcortical cholinergic inputs may regulate various aspects of spatial learning, memory and navigation.

88 citations


Journal ArticleDOI
TL;DR: The results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.
Abstract: Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.

88 citations


Journal ArticleDOI
16 May 2018-Neuron
TL;DR: It is found that DG place fields do not remap across spatial tasks that require DG-dependent memory discrimination, and these findings indicate that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.

Journal ArticleDOI
TL;DR: It is proposed that a fundamental event boundary detection mechanism enables navigation in both the spatial and episodic domains, and serves to form cohesive representations that can be used to predict and guide future behavior.

Journal ArticleDOI
TL;DR: It is concluded that impaired grid cell function may play a key role in age-related decline of specific higher-order cognitive functions, such as spatial navigation.

Journal ArticleDOI
TL;DR: A new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment, which shows that the mice indeed accumulate evidence and is a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.
Abstract: The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.

Journal ArticleDOI
TL;DR: It is suggested that a critical direction for navigation research is to further characterize how hippocampal and striatal subdivisions interact in different navigational contexts.
Abstract: Decades of research have established the importance of the hippocampus for episodic and spatial memory. In spatial navigation tasks, the role of the hippocampus has been classically juxtaposed with the role of the dorsal striatum, the latter of which has been characterized as a system important for implementing stimulus-response and action-outcome associations. In many neuroimaging paradigms, this has been explored through contrasting way finding and route-following behavior. The distinction between the contributions of the hippocampus and striatum to spatial navigation has been supported by extensive literature. Convergent research has also underscored the fact that these different memory systems can interact in dynamic ways and contribute to a broad range of navigational scenarios. For example, although familiar routes may often be navigable based on stimulus-response associations, hippocampal episodic memory mechanisms can also contribute to egocentric route-oriented memory, enabling recall of context-dependent sequences of landmarks or the actions to be made at decision points. Additionally, the literature has stressed the importance of subdividing the striatum into functional gradients-with more ventral and medial components being important for the behavioral expression of hippocampal-dependent spatial memories. More research is needed to reveal how networks involving these regions process and respond to dynamic changes in memory and control demands over the course of navigational events. In this Perspective article, we suggest that a critical direction for navigation research is to further characterize how hippocampal and striatal subdivisions interact in different navigational contexts.

Journal ArticleDOI
TL;DR: It is argued that visuospatial working memory (VSWM) is a fundamental component of the eye movement system and is finely tuned to meet the challenges of active vision.
Abstract: Humans make frequent movements of the eyes (saccades) to explore the visual environment. Here we argue that visuo-spatial working memory (VSWM) is a fundamental component of the eye movement system. Memory representations in VSWM are functionally integrated at all stages of orienting, from selection of the target, to maintenance of visual features across the saccade, to processes supporting the experience of perceptual continuity after the saccade, to the correction of gaze when the eyes fail to land on the intended object. VSWM is finely tuned to meet the challenges of active vision.

Journal ArticleDOI
TL;DR: The cognitive and neural mechanisms that underlie the ability to recover one's bearings when lost are reviewed, with the aim of linking together previously disparate findings from animal behavior, human psychology, electrophysiology, and cognitive neuroscience.

Journal ArticleDOI
TL;DR: Data are inconsistent with the notion that children under 7 do not engage in any attempts to remember, and are most consistent with proposals that children's style of remembering shifts around age 7 from reactive cue-driven methods to proactive, covert methods, which may include cumulative rehearsal.
Abstract: The emergence of strategic verbal rehearsal at around 7 years of age is widely considered a major milestone in descriptions of the development of short‐term memory across childhood. Likewise, rehearsal is believed by many to be a crucial factor in explaining why memory improves with age. This apparent qualitative shift in mnemonic processes has also been characterized as a shift from passive visual to more active verbal mnemonic strategy use, but no investigation of the development of overt spatial rehearsal has informed this explanation. We measured serial spatial order reconstruction in adults and groups of children 5–7 years old and 8–11 years old, while recording their eye movements. Children, particularly the youngest children, overtly fixated late‐list spatial positions longer than adults, suggesting that younger children are less likely to engage in covert rehearsal during stimulus presentation than older children and adults. However, during retention the youngest children overtly fixated more of the to‐be‐remembered sequences than any other group, which is inconsistent with the idea that children do nothing to try to remember. Altogether, these data are inconsistent with the notion that children under 7 do not engage in any attempts to remember. They are most consistent with proposals that children's style of remembering shifts around age 7 from reactive cue‐driven methods to proactive, covert methods, which may include cumulative rehearsal.

Journal ArticleDOI
TL;DR: The summary of this literature suggests that the retrosplenial-parietal circuitry does not represent a strict hierarchical parcellation of function between the two regions but instead a heterogeneous mixture of egocentric-allocentric coding and integration across frames of reference.
Abstract: The retrosplenial cortex is anatomically positioned to integrate sensory, motor, and visual information and is thought to have an important role in processing spatial information and guiding behavior through complex environments. Anatomical and theoretical work has argued that the retrosplenial cortex participates in spatial behavior in concert with input from the parietal cortex. Although the nature of these interactions is unknown, a central position is that the functional connectivity is hierarchical with egocentric spatial information processed in the parietal cortex and higher-level allocentric mappings generated in the retrosplenial cortex. Here, we review the evidence supporting this proposal. We begin by summarizing the key anatomical features of the retrosplenial-parietal network, and then review studies investigating the neural correlates of these regions during spatial behavior. Our summary of this literature suggests that the retrosplenial-parietal circuitry does not represent a strict hierarchical parcellation of function between the two regions but instead a heterogeneous mixture of egocentric-allocentric coding and integration across frames of reference. We also suggest that this circuitry should be represented as a gradient of egocentric-to-allocentric information processing from parietal to retrosplenial cortices, with more specialized encoding of global allocentric frameworks within the retrosplenial cortex and more specialized egocentric and local allocentric representations in parietal cortex. We conclude by identifying the major gaps in this literature and suggest new avenues of research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Journal ArticleDOI
TL;DR: The results suggest that nucleus reuniens may be a potential target in the treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity disorder, addiction, and obsessive‐compulsive disorder, whose symptoms are defined by hippocampal‐prefrontal dysfunctions.
Abstract: The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral midline thalamus is an important anatomical link between the HF and mPFC, and as such is crucially involved in SWM functions that recruit both structures. Little is known, however, regarding the role of RE in other behaviors mediated by this circuit. In the present study, we examined the role of RE in spatial working memory and executive functioning following reversible inactivation of RE with either muscimol or procaine. Rats were implanted with an indwelling cannula targeting RE and trained in a delayed nonmatch to sample spatial alternation T-maze task. For the task, sample and choice runs were separated by moderate or long delays (30, 60, and 120 s). Following asymptotic performance, rats were tested following infusions of drug or vehicle. Muscimol infused into RE impaired SWM at all delays, whereby procaine only impaired performance at the longest delays. Furthermore, RE inactivation with muscimol produced a failure in win-shift strategy as well as severe spatial perseveration, whereby rats persistently made re-entries into incorrect arms during correction trials, despite the absence of reward. This demonstrated marked changes in behavioral flexibility and response strategy. These results strengthen the role of nucleus reuniens as a pivotal link between hippocampus and prefrontal cortex in cognitive and executive functions and suggest that nucleus reuniens may be a potential target in the treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity disorder, addiction, and obsessive-compulsive disorder, whose symptoms are defined by hippocampal-prefrontal dysfunctions.

Journal ArticleDOI
TL;DR: The results using single and multiplexed DREADDS suggest that excitatory activity in the DH and mPFC, alone or in combination, is required for the successful consolidation of object recognition and spatial memories.

Journal ArticleDOI
TL;DR: A novel mental imagery paradigm and high-resolution functional MRI are used to compare accounts of hippocampal function that emphasize associative processes with a theory that proposes scene construction as a primary role and conclude that a greater emphasis on characterizing how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.
Abstract: The hippocampus is known to be important for a range of cognitive functions, including episodic memory, spatial navigation, and thinking about the future. However, researchers have found it difficult to agree on the exact nature of this brain structure's contribution to cognition. Some theories emphasize the role of the hippocampus in associative processes. Another theory proposes that scene construction is its primary role. To directly compare these accounts of hippocampal function in human males and females, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high-resolution functional MRI. The results were striking in showing that different parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or nonscene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing, or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favor one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasize the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterizing how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.SIGNIFICANCE STATEMENT The hippocampus is known to be important for a range of cognitive functions, including episodic memory, spatial navigation, and thinking about the future. However, researchers have found it difficult to agree on the exact nature of this brain structure's contribution to cognition. Here we used a novel mental imagery paradigm and high-resolution functional MRI to compare accounts of hippocampal function that emphasize associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that different parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or nonscene-evoking associative processing. We conclude that a greater emphasis on characterizing how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.

Journal ArticleDOI
TL;DR: Data suggest that early experiences continue to shape the development of memory, learning, and executive functioning processes in preadolescence, which may explain broader cognitive and learning difficulties commonly associated with severe early life neglect.
Abstract: We examined visual recognition memory and executive functioning (spatial working memory [SWM], spatial planning, rule learning, and attention shifting) in 12-year-olds (n = 150) who participated in the Bucharest Early Intervention Project, a randomized controlled trial of foster care for institutionally reared children. Similar to prior reports at 8 years of age, institutionally reared children showed significant deficits in visual recognition memory and SWM. Deficits in attention shifting and rule learning were also apparent at this time point. These data suggest that early experiences continue to shape the development of memory, learning, and executive functioning processes in preadolescence, which may explain broader cognitive and learning difficulties commonly associated with severe early life neglect.

Journal ArticleDOI
TL;DR: In this paper, the authors analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries.
Abstract: Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one's own body.SIGNIFICANCE STATEMENT Spatial computations using environmental boundaries are an integral part of the brain's spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to functional neuroimaging studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions, we identified a neural marker of boundary representation in the human subiculum.

Journal ArticleDOI
TL;DR: A functional link between genetically distinct neurons in the LCN and cognitive behaviors is demonstrated, which suggests an evolutionarily conserved population of dopamine-receptive neurons in this region.

Journal ArticleDOI
TL;DR: These studies suggest that the human medial temporal lobe is equipped with a population of place and grid cells similar to that previously observed in the rodent brain, and that the functional overlap of spatial and declarative memory in the MTL calls for a unified theory of MTL function.
Abstract: While extensive research on the neurophysiology of spatial memory has been carried out in rodents, memory research in humans had traditionally focused on more abstract, language-based tasks. Recent studies have begun to address this gap using virtual navigation tasks in combination with electrophysiological recordings in humans. These studies suggest that the human MTL is equipped with a population of place and grid cells similar to that previously observed in the rodent brain. Furthermore, theta oscillations have been linked to spatial navigation and, more specifically, to the encoding and retrieval of spatial information. While some studies suggest a single navigational theta rhythm which is of lower frequency in humans than rodents, other studies advocate for the existence of two functionally distinct delta-theta frequency bands involved in both spatial and episodic memory. Despite the general consensus between rodent and human electrophysiology, behavioral work in humans does not unequivocally support the use of a metric Euclidean map for navigation. Formal models of navigational behavior, which specifically consider the spatial scale of the environment and complementary learning mechanisms, may help to better understand different navigational strategies and their neurophysiological mechanisms. Finally, the functional overlap of spatial and declarative memory in the MTL calls for a unified theory of MTL function. Such a theory will critically rely upon linking task-related phenomena at multiple temporal and spatial scales. Understanding how single cell responses relate to ongoing theta oscillations during both the encoding and retrieval of spatial and non-spatial associations appears to be key towards developing a more mechanistic understanding of memory processes in the MTL.

Journal ArticleDOI
TL;DR: Depression-like mice have deficits in working memory and contextual fear memory, and ketamine treatment attenuated the memory impairment, and increased the density of NR2B and the amplitude of LTP and NMDA receptor-mediated EPSCs in the hippocampus of depression- like mice.
Abstract: Depression is a common mental disorder that is associated with memory dysfunction. Ketamine has recently been demonstrated to be a rapid antidepressant. The mechanisms underlying how depression induces memory dysfunction and how ketamine relieves depressive symptoms remain poorly understood. This work compared three groups of male C57BL/6J mice: mice exposed to chronic social defeat stress (CSDS) to induce a depression-like phenotype, depression-like mice treated with ketamine, and control mice that were not exposed to CSDS or treated with ketamine. Spatial working memory and long term memory were assessed by spontaneous alternation Y-maze and fear conditioning tests, respectively. We used western blot to analyze the density of N-methyl-D-aspartate receptor (NMDAR) subunits in the hippocampus. We recorded long term potentiation (LTP) and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices. We observed that compared with control mice, depression-like mice had significant reductions in spatial working memory and contextual fear memory. The level of NR2B, LTP and NMDA receptor-mediated EPSCs of depression-like mice were decreased. Ketamine treatment attenuated the memory impairment, and increased the density of NR2B and the amplitude of LTP and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice. In conclusion, depression-like mice have deficits in working memory and contextual fear memory. The decrease of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus may be involved in this process. Ketamine can improve expression of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice, which might be part of the reason why ketamine can alleviate the memory dysfunction induced by depression.

Journal ArticleDOI
TL;DR: It is suggested that a brain network composed of the hippocampus, IC, PRh, and mPFC is required for the generation of OR memory by connecting with other brain regions.

Journal ArticleDOI
TL;DR: Neural activity in the prefrontal–hippocampal circuit in mice during acquisition of spatial reference memory formation was examined and found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation.
Abstract: Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal–hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

Journal ArticleDOI
TL;DR: It is found that prolonged acute SD together with one night sleep recovery exhibits accumulative atrophic effect and recovering plasticity on brain morphology, in line with behavioral changes on attentional tasks.
Abstract: Background: Insufficient sleep is common in daily life and can lead to cognitive impairment. Sleep disturbance also exists in neuropsychiatric diseases. However, whether and how acute and chronic sleep loss affect brain morphology remain largely unknown. Methods: We used voxel-based morphology method to study the brain structural changes during sleep deprivation (SD) at six time point of rested wakefulness, 20h, 24h, 32h, 36h SD, and after one night sleep in 22 healthy subjects, and in 39 patients with chronic primary insomnia relative to 39 status-matched good sleepers. Attention network and spatial memory tests were performed at each SD time point. The longitudinal data were analyzed using one-way repeated measures ANOVA, and post-hoc analysis was used to determine the between-group differences. Results: Acute SD is associated with widespread gray matter volume (GMV) changes in thalamus, cerebellum, insula and parietal cortex. Insomnia is associated with increased GMV in temporal cortex, insula and cerebellum. Acute SD is associated with brain atrophy and as SD hours prolonged more areas show reduced GMV, and after one night sleep the brain atrophy was restored and replaced by increased GMV. SD has accumulative negative effects on attention and working memory. Conclusions: Acute SD and insomnia exhibit distinct morphological changes of GMV. SD has accumulative negative effects on brain morphology and advanced cognitive function. The altered GMV may provide neurobiological basis for attention and memory impairments following sleep loss.