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Memory consolidation involves interactions between the hippocampus and other cortical areas. A new study identifies neurons in the medial entorhinal cortex that over learning increase their coordination with hippocampal replay events, suggesting a route for consolidation of spatial memories. [ABSTRACT FROM AUTHOR]

Cholecystokinin-expressing interneurons (CCKIs) are hypothesized to shape pyramidal cell-firing patterns and regulate network oscillations and related network state transitions. To directly probe their role in the CA1 region, we silenced their activity using optogenetic and chemogenetic tools in mice. Opto-tagged CCKIs revealed a heterogeneous population, and their optogenetic silencing triggered wide disinhibitory network changes affecting both pyramidal cells and other interneurons. CCKI silencing enhanced pyramidal cell burst firing and altered the temporal coding of place cells: theta phase precession was disrupted, whereas sequence reactivation was enhanced. Chemogenetic CCKI silencing did not alter the acquisition of spatial reference memories on the Morris water maze but enhanced the recall of contextual fear memories and enabled selective recall when similar environments were tested. This work suggests the key involvement of CCKIs in the control of place-cell temporal coding and the formation of contextual memories. [Display omitted] • CCKI silencing triggers broad disinhibitory network effects and enhances burst firing • CCKIs are involved in theta phase precession-mediated temporal coding • Disruption of theta phase precession did not prevent subsequent sleep replay • CCKI activity regulates the magnitude of contextual fear-memory recall Rangel Guerrero et al. silenced the activity of CA1 Cholecystokinin-expressing interneurons. Optogenetic silencing disrupted the theta oscillation-related temporal coding of place cells during exploration while sleep replay was enhanced. Chemogenetic silencing enhanced the recall of contextual fear memories the next day and enabled the differentiation of similar environments. [ABSTRACT FROM AUTHOR]

The mammalian hippocampal formation contains several distinct populations of neurons involved in representing self-position and orientation. These neurons, which include place, grid, head direction, and boundary cells, are thought to collectively instantiate cognitive maps supporting flexible navigation. However, to flexibly navigate, it is necessary to also maintain internal representations of goal locations, such that goal-directed routes can be planned and executed. Although it has remained unclear how the mammalian brain represents goal locations, multiple neural candidates have recently been uncovered during different phases of navigation. For example, during planning, sequential activation of spatial cells may enable simulation of future routes toward the goal. During travel, modulation of spatial cells by the prospective route, or by distance and direction to the goal, may allow maintenance of route and goal-location information, supporting navigation on an ongoing basis. As the goal is approached, an increased activation of spatial cells may enable the goal location to become distinctly represented within cognitive maps, aiding goal localization. Lastly, after arrival at the goal, sequential activation of spatial cells may represent the just-taken route, enabling route learning and evaluation. Here, we review and synthesize these and other evidence for goal coding in mammalian brains, relate the experimental findings to predictions from computational models, and discuss outstanding questions and future challenges. To flexibly navigate, animals must have knowledge of both their self- and goal locations. Although neural correlates of self-location are well established, less is known about goal coding. Nyberg et al. comprehensively review both theoretical and empirical findings for such computations in the hippocampal formation. [ABSTRACT FROM AUTHOR]

A recent study using new holographic optogenetic stimulation technology has provided direct evidence that hippocampal place cell activity is sufficient to drive memory and navigation-related behaviors. [ABSTRACT FROM AUTHOR]

Hippocampal activity is critical for spatial memory. Within a fixed, familiar environment, hippocampal codes gradually change over timescales of days to weeks—a phenomenon known as representational drift. The passage of time and the amount of experience are two factors that profoundly affect memory. However, thus far, it has remained unclear to what extent these factors drive hippocampal representational drift. Here, we longitudinally recorded large populations of hippocampal neurons in mice while they repeatedly explored two different familiar environments that they visited at different time intervals over weeks. We found that time and experience differentially affected distinct aspects of representational drift: the passage of time drove changes in neuronal activity rates, whereas experience drove changes in the cells' spatial tuning. Changes in spatial tuning were context specific and largely independent of changes in activity rates. Thus, our results suggest that representational drift is a multi-faceted process governed by distinct neuronal mechanisms. [Display omitted] • Hippocampal neurons exhibit representational drift in familiar environments over weeks • The passage of time drives changes in neuronal activity rates • Experience drives changes in neuronal spatial tuning • Drift in a given environment is unaffected by experience in another environment Geva et al. find a double dissociation between the effects of time and experience on distinct aspects of hippocampal representational drift (i.e., the gradual change in neuronal representations of familiar environments): the passage of time drives changes in neuronal activity rates, whereas experience drives changes in the cells' spatial tuning. [ABSTRACT FROM AUTHOR]

Replays of place cell sequences in the hippocampus are thought to underlie memory consolidation for spatial learning. In this issue of Neuron , Mou et al. show that not only self-running but also social observation experiences promote awake remote replays for planning future journeys. [ABSTRACT FROM AUTHOR]

The hippocampal CA2 region plays a key role in social memory. The encoding of such memory involves afferent activity from the hypothalamic supramammillary nucleus (SuM) to CA2. However, the neuronal circuits required for consolidation of freshly encoded social memory remain unknown. Here, we used circuit-specific optical and single-cell electrophysiological recordings in mice to explore the role of sleep in social memory consolidation and its underlying circuit mechanism. We found that SuM neurons projecting to CA2 were highly active during rapid-eye-movement (REM) sleep but not during non-REM sleep or quiet wakefulness. REM-sleep-selective optogenetic silencing of these neurons impaired social memory. By contrast, the silencing of another group of REM sleep-active SuM neurons that projects to the dentate gyrus had no effect on social memory. Therefore, we provide causal evidence that the REM sleep-active hypothalamic neurons that project to CA2 are specifically required for the consolidation of social memory. [Display omitted] • Both SuM-CA2- and SuM-DG-projecting neurons are highly active during REM sleep • REM-sleep-selective silencing of SuMCA2 neurons impairs social memory • REM-sleep-selective silencing of SuMDG neurons impairs spatial but not social memory • CA2SuM-recipient neurons are highly active during REM sleep Qin et al. identify two groups of REM sleep-active supramammillary neurons, one projecting to the hippocampal CA2 and the other to the dentate gyrus. They find that these two cell groups critically contribute to REM-sleep-associated consolidation of social and spatial memories, respectively. [ABSTRACT FROM AUTHOR]

Summary The hippocampal CA2 subregion has a different anatomical connectivity pattern within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion. Yet major differences in the neuronal activity patterns of CA2 compared with the other CA subregions have not been reported. We show that standard spatial and temporal firing patterns of individual hippocampal principal neurons in behaving rats, such as place fields, theta modulation, and phase precession, are also present in CA2, but that the CA2 subregion differs substantially from the other CA subregions in its population coding. CA2 ensembles do not show a persistent code for space or for differences in context. Rather, CA2 activity patterns become progressively dissimilar over time periods of hours to days. The weak coding for a particular context is consistent with recent behavioral evidence that CA2 circuits preferentially support social, emotional, and temporal rather than spatial aspects of memory. [ABSTRACT FROM AUTHOR]

Flexibility is a hallmark of memories that depend on the hippocampus. For navigating animals, flexibility is necessitated by environmental changes such as blocked paths and extinguished food sources. To better understand the neural basis of this flexibility, we recorded hippocampal replays in a spatial memory task where barriers as well as goals were moved between sessions to see whether replays could adapt to new spatial and reward contingencies. Strikingly, replays consistently depicted new goal-directed trajectories around each new barrier configuration and largely avoided barrier violations. Barrier-respecting replays were learned rapidly and did not rely on place cell remapping. These data distinguish sharply between place field responses, which were largely stable and remained tied to sensory cues, and replays, which changed flexibly to reflect the learned contingencies in the environment and suggest sequenced activations such as replay to be an important link between the hippocampus and flexible memory. • Rats learn to solve a goal-directed navigation task with randomly-changing barriers. • Replay adapts to the new barriers and is predictive of future behavior. • Place fields are largely stable across barrier configurations. Widloski and Foster show that place cells in rat hippocampus learn replay sequences around barriers, even after a large (>90) number of barrier reconfigurations. By contrast, cells' place fields are largely stable, dissociating the stable representation of space from a powerful mechanism for the acquisition and recall of flexible memory. [ABSTRACT FROM AUTHOR]

Hippocampal place cells underlie spatial navigation and memory. Remarkably, CA1 pyramidal neurons can form new place fields within a single trial by undergoing rapid plasticity. However, local feedback circuits likely restrict the rapid recruitment of individual neurons into ensemble representations. This interaction between circuit dynamics and rapid feature coding remains unexplored. Here, we developed "all-optical" approaches combining novel optogenetic induction of rapidly forming place fields with 2-photon activity imaging during spatial navigation in mice. We find that induction efficacy depends strongly on the density of co-activated neurons. Place fields can be reliably induced in single cells, but induction fails during co-activation of larger subpopulations due to local circuit constraints imposed by recurrent inhibition. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles. We demonstrate the behavioral implications of these dynamics, showing that our ensemble place field induction protocol can enhance subsequent spatial association learning. • Rapidly forming place fields can be optogenetically induced in mouse CA1 neurons • Feedback inhibition limits rapid place field induction to fewer principal neurons • Suppressing local inhibition allows induction of place fields in larger ensembles • Ensemble place field induction can enhance subsequent spatial association learning Rolotti, Ahmed, Szoboszlay et al. develop "all-optical" strategies to induce rapidly forming place fields in mouse CA1 and find that local feedback inhibition restricts recruitment of neurons into ensemble representations. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles to enhance subsequent association learning. [ABSTRACT FROM AUTHOR]

The neural circuit mechanisms underlying observational learning, learning through observing the behavior of others, are poorly understood. Hippocampal place cells are important for spatial learning, and awake replay of place cell patterns is involved in spatial decisions. Here we show that, in observer rats learning to run a maze by watching a demonstrator's spatial trajectories from a separate nearby observation box, place cell patterns during self-running in the maze are replayed remotely in the box. The contents of the remote awake replay preferentially target the maze's reward sites from both forward and reverse replay directions and reflect the observer's future correct trajectories in the maze. In contrast, under control conditions without a demonstrator, the remote replay is significantly reduced, and the preferences for reward sites and future trajectories disappear. Our results suggest that social observation directs the contents of remote awake replay to guide spatial decisions in observational learning. [Display omitted] • Rats learn to run a T-maze by observing a demonstrator's spatial trajectory • CA1 place cell sequences in the maze are replayed remotely in the observation box • Remote replay prefers reward sites in the maze and predicts future decisions • The preference and predictive power disappear without a social demonstrator Mou et al. demonstrate that observing an animal running a maze reactivates the firing sequences of the observer's hippocampal place cells remotely during awake ripples in a physically separated observation box. Such reactivation preferentially focuses on reward sites in the maze and predicts the observer's future spatial decisions. [ABSTRACT FROM AUTHOR]

Humans and animals use cognitive maps to represent the spatial structure of the environment. Although these maps are typically conceptualized as extending in an equipotential manner across known space, psychological evidence suggests that people mentally segment complex environments into subspaces. To understand the neurocognitive mechanisms behind this operation, we familiarized participants with a virtual courtyard that was divided into two halves by a river; we then used behavioral testing and fMRI to understand how spatial locations were encoded within this environment. Participants' spatial judgments and multivoxel activation patterns were affected by the division of the courtyard, indicating that the presence of a boundary can induce mental segmentation even when all parts of the environment are co-visible. In the hippocampus and occipital place area (OPA), the segmented organization of the environment manifested in schematic spatial codes that represented geometrically equivalent locations in the two subspaces as similar. In the retrosplenial complex (RSC), responses were more consistent with an integrated spatial map. These results demonstrate that people use both local spatial schemas and integrated spatial maps to represent segmented environment. We hypothesize that schematization may serve as a general mechanism for organizing complex knowledge structures in terms of their component elements. [Display omitted] • Participants were familiarized with a virtual environment bisected by a river • Behavioral tests indicated that they mentally divided the space into two subspaces • OPA and hippocampus represented these subspaces using local spatial schemas • Cognitive maps may be constituted from both local representations and global codes Navigable environments can often be segmented into subspaces or regions. Peer and Epstein show that, when people learn a virtual environment containing multiple subspaces, OPA and hippocampus encode local maps that reflect the common geometric structure of the subspaces. These spatial schemas may be a key component of cognitive maps. [ABSTRACT FROM AUTHOR]

Reward value is known to modulate learning speed in spatial memory tasks, but little is known about its influence on the dynamical changes in hippocampal spatial representations. Here, we monitored the trial-to-trial changes in hippocampal place cell activity during the acquisition of place-reward associations with varying reward size. We show a faster reorganization and stabilization of the hippocampal place map when a goal location is associated with a large reward. The reorganization is driven by both rate changes and the appearance and disappearance of place fields. The occurrence of hippocampal replay activity largely followed the dynamics of changes in spatial representations. Replay patterns became more selectively tuned toward behaviorally relevant experiences over the course of learning via the refined contributions of specific cell subpopulations. These results suggest that high reward value enhances memory retention by accelerating the formation and stabilization of the hippocampal cognitive map and selectively enhancing its reactivation during learning. • High reward accelerates reorganization of hippocampal spatial map during learning • Forward and reverse replay differ in dynamics during learning • Awake hippocampal replay may not contribute to updating of the spatial map • Reverse replay relates more strongly to recent experiences than forward replay Michon et al. show in rats that the hippocampal spatial map is quickly updated during learning of reward-place associations, which is further accelerated by high reward value. They found differing dynamics of forward and reverse replay events during learning but no indication that replay directly influences hippocampal spatial representations. [ABSTRACT FROM AUTHOR]

Executing memory-guided behavior requires storage of information about experience and later recall of that information to inform choices. Awake hippocampal replay, when hippocampal neural ensembles briefly reactivate a representation related to prior experience, has been proposed to critically contribute to these memory-related processes. However, it remains unclear whether awake replay contributes to memory function by promoting the storage of past experiences, facilitating planning based on evaluation of those experiences, or both. We designed a dynamic spatial task that promotes replay before a memory-based choice and assessed how the content of replay related to past and future behavior. We found that replay content was decoupled from subsequent choice and instead was enriched for representations of previously rewarded locations and places that had not been visited recently, indicating a role in memory storage rather than in directly guiding subsequent behavior. [Display omitted] • Replay does not reliably represent the upcoming path of the subject • Replay tends to represent previous goals and non-recently visited locations • Replay is poorly suited to guiding immediately subsequent behavior • Replay is better suited to storing and updating representations of past experience Gillespie et al. find that hippocampal replay does not reliably relate to immediately subsequent choice in a spatial memory task. Instead, replay preferentially represents previous goals and places that have not been visited recently, suggesting a role in storing and updating memories rather than in directly guiding upcoming behavior. [ABSTRACT FROM AUTHOR]

Birds strongly rely on spatial memory and navigation. Therefore, it is of utmost interest to reveal how space is represented in the avian brain. Here we used tetrodes to record neurons from the hippocampal formation of Japanese quails—a ground-dwelling species—while the quails roamed in an open-field arena. Whereas spatially modulated cells (place cells, grid cells, border cells) were generally not encountered, the firing rate of about 12% of the neurons was unimodally and significantly modulated by the head azimuth—i.e., these were head-direction cells (HD cells). Typically, HD cells were maximally active at one preferred direction and minimally at the opposite null direction, with preferred directions spanning all 360° across the population. The preferred direction was independent of the animal's position and speed and was stable during the recording session. The HD tuning was broader compared to that of HD cells in rodents, and most cells had non-zero baseline firing in all directions. However, similar to findings in rodents, the HD tuning usually rotated with the rotation of a salient visual cue in the arena. Thus, these findings support the existence of an allocentric HD representation in the quail hippocampal formation and provide the first demonstration of HD cells in birds. • Nearly 12% of the cells in the hippocampus of quails are modulated by the head direction • The preferred directions are stable over time, speed, and location • The preferred directions cover uniformly all directions • Place cells and border cells are generally not encountered Ben-Yishay et al. report single-neuron recordings in the hippocampal formation of freely roaming quails. They show, for the first time in an avian species, stable head-direction tuning — providing a basis for a comparative study of the hippocampus and its role in the control of spatial behaviors across vertebrates. [ABSTRACT FROM AUTHOR]

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information. [Display omitted] • In phase precession, neurons code information by spiking faster than local oscillations • Neurons in the human brain exhibit phase precession during a spatial memory task • As in rodents, precession occurs relative to space in the hippocampal formation • In the frontal cortex, non-spatial precession occurs while seeking specific goals Neurons in the human brain spike in rhythm with local network oscillations to represent spatial position and non-spatial states, highlighting phase procession as a widespread neuronal mechanism for coordinating spike timing during behavior and cognition. [ABSTRACT FROM AUTHOR]

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an 'all-optical' combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory. • Two-photon optogenetics in VR enables targeted manipulation of place cell ensembles • Activating specific place cell ensembles drives their spatially associated behavior • Place cell stimulation inhibits endogenous place code expression and triggers remapping • Direct evidence for a causal role of place cells in spatial navigation Selective stimulation of a small number of hippocampal place cells in mice provides causal evidence that hippocampal place cells actively support spatial navigation and memory. [ABSTRACT FROM AUTHOR]

The hippocampal-entorhinal system is important for spatial and relational memory tasks. We formally link these domains, provide a mechanistic understanding of the hippocampal role in generalization, and offer unifying principles underlying many entorhinal and hippocampal cell types. We propose medial entorhinal cells form a basis describing structural knowledge, and hippocampal cells link this basis with sensory representations. Adopting these principles, we introduce the Tolman-Eichenbaum machine (TEM). After learning, TEM entorhinal cells display diverse properties resembling apparently bespoke spatial responses, such as grid, band, border, and object-vector cells. TEM hippocampal cells include place and landmark cells that remap between environments. Crucially, TEM also aligns with empirically recorded representations in complex non-spatial tasks. TEM also generates predictions that hippocampal remapping is not random as previously believed; rather, structural knowledge is preserved across environments. We confirm this structural transfer over remapping in simultaneously recorded place and grid cells. • Common principles for space and relational memory in the hippocampal formation • Explains hippocampal generalization in both spatial and non-spatial problems • Accounts for many reported hippocampal and entorhinal cell types from such tasks • Predicts how hippocampus remaps in both spatial and non-spatial tasks The Tolman-Eichenbaum Machine, named in honor of Edward Chace Tolman and Howard Eichenbaum for their contributions to cognitive theory, provides a unifying framework for the hippocampal role in spatial and nonspatial generalization and unifying principles underlying many entorhinal and hippocampal cell types. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) leads to profound deficits in spatial memory and synaptic and cellular alterations to the hippocampus that last into adulthood. Neurons in the hippocampus called place cells discharge as an animal enters specific places in an environment, establish distinct ensemble codes for familiar and novel places, and are modulated by local theta rhythms. Spatial memory is thought to critically depend on the integrity of hippocampal place cell firing. Therefore, we tested the hypothesis that hippocampal place cell firing is impaired after PAE by performing in vivo recordings from the hippocampi (CA1 and CA3) of moderate PAE and control adult rats. Our results show that hippocampal CA3 neurons from PAE rats have reduced spatial tuning. Second, CA1 and CA3 neurons from PAE rats are less likely to orthogonalize their firing between directions of travel on a linear track and between changes in contextual stimuli in an open arena compared to control neurons. Lastly, reductions in the number of hippocampal place cells exhibiting significant theta rhythmicity and phase precession were observed, which may suggest changes to hippocampal microcircuit function. Together, the reduced spatial tuning and sensitivity to contextual changes provide a neural systems-level mechanism to explain spatial memory impairment after moderate PAE. • Prenatal alcohol exposure reduces place field spatial tuning and stability • Prenatal alcohol exposure decreases place field directionality on the linear track • Prenatal alcohol exposure increases control of place fields by a proximal cue • Prenatal alcohol exposure slows theta oscillations and alters phase precession Harvey et al. demonstrate that prenatal alcohol exposure disrupts hippocampal place cell firing and slows theta oscillations. The findings represent a critical step in developing a complete multi-level understanding of the neurobiological basis of spatial learning and memory impairments after moderate prenatal alcohol exposure. [ABSTRACT FROM AUTHOR]

Spatial learning is impaired in humans with preclinical Alzheimer's disease (AD). We reported similar impairments in 3xTg-AD mice learning a spatial reorientation task. Memory reactivation during sleep is critical for learning-related plasticity, and memory consolidation is correlated with hippocampal sharp wave ripple (SWR) density, cortical delta waves (DWs), cortical spindles, and the temporal coupling of these events—postulated as physiological substrates for memory consolidation. Further, hippocampal-cortical discoordination is prevalent in individuals with AD. Thus, we hypothesized that impaired memory consolidation mechanisms in hippocampal-cortical networks could account for spatial memory deficits. We assessed sleep architecture, SWR-DW dynamics, and memory reactivation in a mouse model of tauopathy and amyloidosis implanted with a recording array targeting isocortex and hippocampus. Mice underwent daily recording sessions of rest-task-rest while learning the spatial reorientation task. We assessed memory reactivation by matching activity patterns from the approach to the unmarked reward zone to patterns during slow-wave sleep (SWS). AD mice had more SWS, but reduced SWR density. The increased SWS compensated for reduced SWR density so there was no reduction in SWR number. In control mice, spindles were phase-coupled with DWs, and hippocampal SWR-cortical DW coupling was strengthened in post-task sleep and was correlated with performance on the spatial reorientation task the following day. However, in AD mice, SWR-DW and spindle-DW coupling were impaired. Thus, reduced SWR-DW coupling may cause impaired learning in AD, and spindle-DW coupling during short rest-task-rest sessions may serve as a biomarker for early AD-related changes in these brain dynamics. • In 3xTg-AD mice, increased sleep may compensate for some impaired brain dynamics • Hippocampal-cortical coupling increases after spatial task • Deficits in spatial learning and hippocampal-cortical coupling in 3xTg-AD mice • Spindle-Delta coupling deficits in cortex parallels hippocampal-cortical deficits Benthem et al. use multi-site recordings to demonstrate increased sleep in AD mice, which may compensate for some impaired brain dynamics. Hippocampal-cortical coupling during sleep predicts spatial learning in normal mice. However, spatial learning and hippocampal-cortical coupling are impaired in AD mice, possibly causing impaired learning. [ABSTRACT FROM AUTHOR]

Hippocampal place cells selectively fire when an animal traverses a particular location and are considered a neural substrate of spatial memory. Place cells were shown to change their activity patterns (remap) across different spatial contexts but to maintain their spatial tuning in a fixed familiar context. Here, we show that mouse hippocampal neurons can globally remap, forming multiple distinct representations (maps) of the same familiar environment, without any apparent changes in sensory input or behavior. Alternations between maps occurred only across separate visits to the environment, implying switching between distinct stable attractors in the hippocampal network. Importantly, the different maps were spatially informative and persistent over weeks, demonstrating that they can be reliably stored and retrieved from long-term memory. Taken together, our results suggest that a memory of a given spatial context could be associated with multiple distinct neuronal representations, rather than just one. • Hippocampal neurons switch between distinct maps of the same familiar environment • Alternations between maps occur only across separate visits to the same environment • Remapping is simultaneous and coherent across place and non-place cells • The distinct maps are spatially informative and stable over weeks Sheintuch et al. show that hippocampal neurons can switch between distinct spatial representations (maps) across separate visits to the same environment, without any apparent changes in sensory input or behavior. The distinct maps are spatially informative and stable over weeks, suggesting that they can be reliably retrieved from long-term memory. [ABSTRACT FROM AUTHOR]

The hippocampus and surrounding medial-temporal-lobe (MTL) structures are critical for both memory and spatial navigation, but we do not fully understand the neuronal representations used to support these behaviors. Much research has examined how the MTL neurally represents spatial information, such as with "place cells" that represent an animal's current location or "head-direction cells" that code for an animal's current heading. In addition to behaviors that require an animal to attend to the current spatial location, navigating to remote destinations is a common part of daily life. To examine the neural basis of these behaviors, we recorded single-neuron activity from neurosurgical patients playing Treasure Hunt, a virtual-reality spatial-memory task. By analyzing how the activity of these neurons related to behavior in Treasure Hunt, we found that the firing rates of many MTL neurons during navigation significantly changed depending on the position of the current spatial target. In addition, we observed neurons whose firing rates during navigation were tuned to specific heading directions in the environment, and others whose activity changed depending on the timing within the trial. By showing that neurons in our task represent remote locations rather than the subject's own position, our results suggest that the human MTL can represent remote spatial information according to task demands. • Epilepsy patients performed a spatial navigation task during single-neuron recordings • Neuronal firing in the medial temporal lobe represents spatial target locations • Single-neuron activity does not represent the subject's own location in this task • Neuronal activity also varied with heading direction and order of navigation periods Tsitsiklis et al. record single-unit activity from epilepsy patients during spatial navigation. They find that the firing rates of MTL neurons vary with the locations of spatial targets, heading direction, and serial position. This suggests that the human MTL represents multiple types of spatiotemporal information to support spatial cognition. [ABSTRACT FROM AUTHOR]

Spatial learning requires remembering and choosing paths to goals. Hippocampal place cells replay spatial paths during immobility in reverse and forward order, offering a potential mechanism. However, how replay supports both goal-directed learning and memory-guided decision making is unclear. We therefore continuously tracked awake replay in the same hippocampal-prefrontal ensembles throughout learning of a spatial alternation task. We found that, during pauses between behavioral trajectories, reverse and forward hippocampal replay supports an internal cognitive search of available past and future possibilities and exhibits opposing learning gradients for prediction of past and future behavioral paths, respectively. Coordinated hippocampal-prefrontal replay distinguished correct past and future paths from alternative choices, suggesting a role in recall of past paths to guide planning of future decisions for spatial working memory. Our findings reveal a learning shift from hippocampal reverse-replay-based retrospective evaluation to forward-replay-based prospective planning, with prefrontal readout of memory-guided paths for learning and decision making. • Continuous hippocampal-prefrontal (CA1-PFC) replay tracking during spatial learning • Reverse replay for retrospective evaluation, forward replay for prospective planning • Opposing learning gradients for CA1 reverse- and forward-replay prediction of paths • CA1-PFC replay supports past recall and future decisions for spatial working memory Shin, Tang, and Jadhav use continuous activity tracking to show that awake CA1 reverse- and forward-replay events predict past and future choices, respectively, with opposing spatial learning gradients. CA1-PFC replay supports recall and planning for spatial working memory tasks. [ABSTRACT FROM AUTHOR]

Summary The brain has an extraordinary ability to create an internal spatial map of the external world [ 1 ]. This map-like representation of environmental surroundings is encoded through specific types of neurons, located within the hippocampus and entorhinal cortex, which exhibit spatially tuned firing patterns [ 2, 3 ]. In addition to encoding space, these neurons are believed to be related to contextual information and memory [ 4–7 ]. One class of such cells is the grid cells, which are located within the entorhinal cortex, presubiculum, and parasubiculum [ 3, 8 ]. Grid cell firing forms a hexagonal array of firing fields, a pattern that is largely thought to reflect the operation of intrinsic self-motion-related computations [ 9–12 ]. If this is the case, then fields should be relatively uniform in size, number of spikes, and peak firing rate. However, it has been suggested that this is not in fact the case [ 3, 13 ]. The possibility exists that local spatial information also influences grid cells, which—if true—would greatly change the way in which grid cells are thought to contribute to place coding. Accordingly, we asked how discriminable the individual fields of a given grid cell are by looking at the distribution of field firing rates and reproducibility of this distribution across trials. Grid fields were less uniform in intensity than expected, and the pattern of strong and weak fields was spatially stable and recurred across trials. The distribution remained unchanged even after arena rescaling, but not after remapping. This suggests that additional local information is being overlaid onto the global hexagonal pattern of grid cells. [ABSTRACT FROM AUTHOR]