Place Cell Firing Research Articles

Trading Place for Space: Increasing Location Resolution Reduces Contextual Capacity in Hippocampal Codes.

Many animals learn cognitive maps of their environment - a simultaneous representation of context, experience, and position. Place cells in the hippocampus, named for their explicit encoding of position, are believed to be a neural substrate of these maps, with place cell "remapping" explaining how this system can represent different contexts. Briefly, place cells alter their firing properties, or "remap", in response to changes in experiential or sensory cues. Substantial sensory changes, produced, e.g., by moving between environments, cause large subpopulations of place cells to change their tuning entirely. While many studies have looked at the physiological basis of remapping, we lack explicit calculations of how the contextual capacity of the place cell system changes as a function of place field firing properties. Here, we propose a geometric approach to understanding population level activity of place cells. Using known firing field statistics, we investigate how changes to place cell firing properties affect the distances between representations of different environments within firing rate space. Using this approach, we find that the number of contexts storable by the hippocampus grows exponentially with the number of place cells, and calculate this exponent for environments of different sizes. We identify a fundamental trade-off between high resolution encoding of position and the number of storable contexts. This trade-off is tuned by place cell width, which might explain the change in firing field scale along the dorsal-ventral axis of the hippocampus. We demonstrate that clustering of place cells near likely points of confusion, such as boundaries, increases the contextual capacity of the place system within our framework and conclude by discussing how our geometric approach could be extended to include other cell types and abstract spaces.

Integration of rate and phase codes by hippocampal cell-assemblies supports flexible encoding of spatiotemporal context.

Spatial information is encoded by location-dependent hippocampal place cell firing rates and sub-second, rhythmic entrainment of spike times. These rate and temporal codes have primarily been characterized in low-dimensional environments under limited cognitive demands; but how is coding configured in complex environments when individual place cells signal several locations, individual locations contribute to multiple routes and functional demands vary? Quantifying CA1 population dynamics of male rats during a decision-making task, here we show that the phase of individual place cells' spikes relative to the local theta rhythm shifts to differentiate activity in different place fields. Theta phase coding also disambiguates repeated visits to the same location during different routes, particularly preceding spatial decisions. Using unsupervised detection of cell assemblies alongside theoretical simulation, we show that integrating rate and phase coding mechanisms dynamically recruits units to different assemblies, generating spiking sequences that disambiguate episodes of experience and multiplexing spatial information with cognitive context.

Category boundaries modulate memory in a place-cell-like manner

Concepts describe how instances of the same kind are related, enabling the categorization and interpretation of new information.1,2 How concepts are represented is a longstanding question. Category boundaries have been considered defining features of concept representations, which can guide categorical inference,3 with fMRI evidence showing category-boundary signals in the hippocampus.4,5 The underlying neural mechanism remains unclear. The hippocampal-entorhinal system, known for its spatially tuned neurons that form cognitive maps of space,6,7 may support conceptual knowledge formation, with place cells encoding locations in conceptual space.4,8,9,10,11 Physical boundaries anchor spatial representations and boundary shifts affect place and grid fields,12,13,14,15,16 as well as human spatial memory,17,18,19 along manipulated dimensions. These place cell responses are likely driven by boundary vector cells, which respond to boundaries at specific allocentric distances and directions,20,21,22,23 the neural correlates of which have been identified in the subiculum and entorhinal cortex20,24,25. We hypothesize similar patterns of memory adaptations in response to shifting category boundaries. Our findings show that after category boundary shifts, participants' memory for category exemplars distorts along the changed dimension, mirroring place field deformations. We demonstrate that the boundary vector cell model of place cell firing best accounts for these distortions compared with alternative geometric explanations. Our study highlights a role of category boundaries in human cognition and establishes a new complementary link between hippocampal coding properties with respect to boundaries and human concept representation, bridging spatial and conceptual domains.

Social odors drive hippocampal CA2 place cell responses to social stimuli.

Hippocampal region CA2 is essential for social memory processing. Interaction with social stimuli induces changes in CA2 place cell firing during active exploration and sharp wave-ripples during rest following a social interaction. However, it is unknown whether these changes in firing patterns are caused by integration of multimodal social stimuli or by a specific sensory modality associated with a social interaction. Rodents rely heavily on chemosensory cues in the form of olfactory signals for social recognition processes. To determine the extent to which social olfactory signals contribute to CA2 place cell responses to social stimuli, we recorded CA2 place cells in rats freely exploring environments containing stimuli that included or lacked olfactory content. We found that CA2 place cell firing patterns significantly changed only when social odors were prominent. Also, place cells that increased their firing in the presence of social odors alone preferentially increased their firing during subsequent sharp wave-ripples. Our results suggest that social olfactory cues are essential for changing CA2 place cell firing patterns during and after social interactions. These results support prior work suggesting CA2 performs social functions and shed light on processes underlying CA2 responses to social stimuli.

Integrated Three-Electrode Dual-Mode Detection Chip for Place Cell Analysis: Dopamine Facilitates the Role of Place Cells in Encoding Spatial Locations of Novel Environments and Rewards.

The functioning of place cells requires the involvement of multiple neurotransmitters, with dopamine playing a critical role in hippocampal place cell activity. However, the exact mechanisms through which dopamine influences place cell activity remain largely unknown. Herein, we present the development of the integrated three-electrode dual-mode detection chip (ITDDC), which enables simultaneous recording of the place cell activity and dopamine concentration fluctuation. The working electrode, reference electrode, and counter electrode are all integrated within the ITDDC in electrochemical detection, enabling the real-time in situ monitoring of dopamine concentrations in animals in motion. The reference, working, and counter electrodes are surface-modified using PtNPs and polypyrrole, PtNPs and PEDOT:PSS, and PtNPs, respectively. This modification allows for the detection of dopamine concentrations as low as 20 nM. We conducted dual-mode testing on mice in a novel environment and an environment with food rewards. We found distinct dopamine concentration variations along different paths within a novel environment, implying that different dopamine levels may contribute to spatial memory. Moreover, environmental food rewards elevate dopamine significantly, followed by the intense firing of reward place cells, suggesting a crucial role of dopamine in facilitating the encoding of reward-associated locations in animals. The real-time and in situ recording capabilities of ITDDC offer new opportunities to investigate the interplay between electrophysiology and dopamine during animal exploration and reward-based memory and provide a novel glimpse into the correlation between dopamine levels and place cell activity.

A theory of hippocampal theta correlations accounting for extrinsic and intrinsic sequences.

Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as one-dimensional behavioral sequences of traversed locations. In a two-dimensional space, however, each single location can be visited along arbitrary one-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this two-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (one-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the two-dimensional spatial topology, whereas the intrahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, intrinsic theta sequences are less prominent, but can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.

A theory of hippocampal theta correlations accounting for extrinsic and intrinsic sequences

Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as one-dimensional behavioral sequences of traversed locations. In a two-dimensional space, however, each single location can be visited along arbitrary one-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this two-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (one-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the two-dimensional spatial topology, whereas the intrahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, intrinsic theta sequences are less prominent, but can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.

Hippocampal phase precession is preserved under ketamine, but the range of precession across a theta cycle is reduced.

Hippocampal phase precession, which depends on the precise spike timing of place cells relative to local theta oscillations, has been proposed to underlie sequential memory. N-methyl-D-asparate (NMDA) receptor antagonists such as ketamine disrupt memory and also reproduce several schizophrenia-like symptoms, including spatial memory impairments and disorganized cognition. It is possible that these impairments result from disruptions to phase precession. We used an ABA design to test whether an acute, subanesthetic dose (7.5 mg/kg) of ketamine disrupted phase precession in CA1 of male rats as they navigated around a rectangular track for a food reward. Ketamine did not affect the ability of CA1 place cells to precess despite changes to place cell firing rates, local field potential properties and locomotor speed. However, ketamine reduced the range of phase precession that occurred across a theta cycle. Phase precession is largely robust to acute NMDA receptor antagonism by ketamine, but the reduced range of precession could have important implications for learning and memory.

Hippocampal place cells exhibit impairments in spatial information coding in an APP‐knock in model of Alzheimer’s Disease

AbstractBackgroundThe hippocampus is one of the first cortical regions to exhibit Alzheimer’s Disease (AD) pathology. The spatially‐related firing of hippocampal place cells provides the cellular basis for spatial memory and this is impaired relatively early in AD, yet few studies examine place cell activity in AD mouse models. We undertook an in‐depth characterisation of hippocampal pyramidal cell activity in an APP knock‐in model of AD.MethodMicrodrives carrying 8 tetrodes were implanted into the left CA1 hippocampal subfield of 14‐month female mice (four APPNL‐G‐F, four wild‐type littermates). Mice undertook daily foraging sessions in an open field and ran on a linear track as CA1 activity was recorded. On completion of experiments, 40µm coronal sections of fixed brain tissue were stained using Cresyl Violet to verify tetrode placement and Thioflavin‐S to quantify amyloid β plaque burden.Result270 cells were recorded (119 wild‐type, 151 APPNL‐G‐F). CA1 pyramidal cells were classified as “place cells” or “non‐place cells” based on their spatial information content (bits/spike). Pyramidal cells recorded in wild‐type mice had significantly greater spatial information content than APPNL‐G‐F pyramidal cells (Figure 1), and a higher proportion were classified as place cells. Wild‐type place cells had significantly greater spatial information content than APPNL‐G‐F place cells. Corresponding differences were identified in place field size (Figures 2, 3). A positive correlation was identified between Aβ plaque burden and pyramidal cell spatial information content in the four APPNL‐G‐F mice (Figure 4).Coordination of place cell firing by the hippocampal theta rhythm was disrupted in APPNL‐G‐F mice; phase‐locking of pyramidal cells and place cells was significantly reduced (Figure 5), there was less coherence in the preferred theta phase across the pyramidal cell population, and a reduction in theta phase precession was observed.ConclusionAPPNL‐G‐F CA1 place cells exhibited deficits in both rate coding and temporal coding of spatial information indicating that amyloid β pathology, in the absence tau tangles, was associated with a disruption of hippocampal place cell function. These results provide preliminary support for the hypothesis that disruption of hippocampal function by AD pathology manifests as altered place cell activity and spatial behaviour.

Disrupted hippocampal synchrony following maternal immune activation in a rat model.

Maternal immune activation (MIA) is a risk factor for schizophrenia and other neurodevelopmental disorders. MIA in rats models a number of the brain and behavioral changes that are observed in schizophrenia, including impaired memory. Recent studies in the MIA model have shown that the firing of the hippocampal place cells that are involved in memory processes appear relatively normal, but with abnormalities in the temporal ordering of firing. In this study, we re-analyzed data from prior hippocampal electrophysiological recordings of MIA and control animals to determine whether temporal dysfunction was evident. We find that there is a decreased ratio of slow to fast gamma power, resulting from an increase in fast gamma power and a tendency toward reduced slow gamma power in MIA rats. Moreover, we observe a robust reduction in spectral coherence between hippocampal theta and both fast and slow gamma rhythms, as well as changes in the phase of theta at which fast gamma occurs. We also find the phasic organization of place cell phase precession on the theta wave to be abnormal in MIA rats. Lastly, we observe that the local field potential of MIA rats contains more frequent sharp-wave ripple events, and that place cells were more likely to fire spikes during ripples in these animals than control. These findings provide further evidence of desynchrony in MIA animals and may point to circuit-level changes that underlie failures to integrate and encode information in schizophrenia.

Neuronal signature of spatial decision-making during navigation by freely moving rats by using calcium imaging

A challenge in spatial memory is understanding how place cell firing contributes to decision-making in navigation. A spatial recency task was created in which freely moving rats first became familiar with a spatial context over several days and thereafter were required to encode and then selectively recall one of three specific locations within it that was chosen to be rewarded that day. Calcium imaging was used to record from more than 1,000 cells in area CA1 of the hippocampus of five rats during the exploration, sample, and choice phases of the daily task. The key finding was that neural activity in the startbox rose steadily in the short period prior to entry to the arena and that this selective population cell firing was predictive of the daily changing goal on correct trials but not on trials in which the animals made errors. Single-cell and population activity measures converged on the idea that prospective coding of neural activity can be involved in navigational decision-making.

Neural network based successor representations to form cognitive maps of space and language

How does the mind organize thoughts? The hippocampal-entorhinal complex is thought to support domain-general representation and processing of structural knowledge of arbitrary state, feature and concept spaces. In particular, it enables the formation of cognitive maps, and navigation on these maps, thereby broadly contributing to cognition. It has been proposed that the concept of multi-scale successor representations provides an explanation of the underlying computations performed by place and grid cells. Here, we present a neural network based approach to learn such representations, and its application to different scenarios: a spatial exploration task based on supervised learning, a spatial navigation task based on reinforcement learning, and a non-spatial task where linguistic constructions have to be inferred by observing sample sentences. In all scenarios, the neural network correctly learns and approximates the underlying structure by building successor representations. Furthermore, the resulting neural firing patterns are strikingly similar to experimentally observed place and grid cell firing patterns. We conclude that cognitive maps and neural network-based successor representations of structured knowledge provide a promising way to overcome some of the short comings of deep learning towards artificial general intelligence.

Experience-Dependent Egr1 Expression in the Hippocampus of Japanese Quail.

The hippocampal formation (HF) is a structure critical to navigation and many forms of memory. In mammals, the firing of place cells is widely regarded as the fundamental unit of HF information processing. Supporting homology between the avian and mammalian HF, context-specific patterns of Egr1 have been reported in birds that are comparable to those produced by place cell firing in mammals. Recent electrophysiological data, however, suggest that many avian species lack place cells, potentially undermining the correspondence between Egr1 and place cell-related firing in the avian brain. To clarify this, the current study examines Egr1 expression in Japanese quail under conditions known to elicit only weakly spatially modulated firing patterns and report robust context-dependent Egr1 expression. These data confirm that context-dependent expression of Egr1 is not dependent on precise place fields and provide insight into how these birds are able to perform complex spatial tasks despite lacking mammalian-like place cells.

Beyond Place Cells: Using Algebraic Geometry to Determine Underlying Structure of Receptive Fields Associated with Sensory Neurons

In 2014, John O’Keefe was jointly awarded a Nobel Prize for his 1971 discovery of place cells, a population of neurons in the hippocampus which contribute to an organism’s intuitive understanding of their position in relation to their surrounding space. Each place cell has a representative receptive field, the area in which the place cell fires when occupied by the organism, which based on their overlapping structure can provide us with information about an individual’s surroundings. The challenge of determining this overlapping structure, starting from neuronal firing patterns without context, still remains, but can be explored using algebraic geometry. Tools from algebraic geometry can describe the receptive fields of place cells to better understand the phenomena and how the signals of the brain contribute to the individual’s perception of their surroundings. To compute these relationships, we use the neural code, a binary representation of neurons firing; additionally, using Euler diagrams (a simple example being the Venn diagram) we can visualize the representation of the receptive field. Under certain constraints (i.e., connectivity), the overlap of receptive fields can be realized in up to three dimensions. This finding seems intuitive when applied to place cells since we perceive our position in respect to our surroundings in a three‐dimensional space. These same tools can be applied to other neuronal populations regardless of an intuitive dimensionality of the receptive fields. It is difficult to imagine a visual representation of all receptive fields, but with certain constraints we can construct a geometric visualization. To address this difficulty, we have developed a code using place cell data to compute the dimension of its receptive field. Then, using publicly available data sets, we used our code to determine the dimensionality of other sensory neuronal populations.

Role of Pharmacological Modulation of Tonic Inhibition in Hippocampal Sharp Wave Ripples Amplitude and Place Cell Firing Dynamics

Hippocampal hyperactivity is a hallmark of memory dysfunction associated with age related mild cognitive impairment (aMCI) and Alzheimer’s disease, leading to the hypothesis that hippocampal trisynaptic circuit hyperactivity impairs memory function. As a test of this hypothesis, we sought to pharmacologically recapitulate hyperactivity in young adults by attenuating tonic inhibition in the hippocampal trisynaptic circuit. We used chronically implanted arrays of 96 electrodes arranged as tetrodes and 32 channel silicon probes to record place cell activity within and across the CA1 subregion of young adult rats either foraging in familiar and novel environments or resting in a familiar environment (without foraging) while awake but immobile for ripple band recordings. We demonstrate that oral administration of the nootropic drug α5IA, a selective negative modulator of tonically active predominantly extrasynaptic α5 GABA receptors, enhances CA1 place cell firing rates but does not augment spatial information content or pattern separation expected a priori to reflect nootropic drug action. This conundrum is resolved by the finding that α5IA substantially increases the sharp wave ripple (SPW‐R) amplitude, which is known to correlate with improved remembering. We replicated to result in three strains of rats (Long Evans, Fisher 344, and Sprague Dawley) and found that the outcomes were not strain specific. These observations indicate that the nootropic actions of α5IA may result from enhancement of aspects of memory function influenced by CA1 SPW‐R amplitude such as consolidation of encoded information. We posit that modulation of ripple dynamics may be controlled via alterations in extrasynaptic tonic inhibition mediated in part by α5 GABA‐A receptors.

Aged Rats Exhibit Altered Behavior-Induced Oscillatory Activity, Place Cell Firing Rates, and Spatial Information Content in the CA1 Region of the Hippocampus.

Hippocampal gamma and theta oscillations are associated with mnemonic and navigational processes and adapt to changes in the behavioral state of an animal to optimize spatial information processing. It has been shown that locomotor activity modulates gamma and theta frequencies in rats, although how age alters this modulation has not been well studied. Here, we examine gamma and theta local-field potential and place cell activity in the hippocampus CA1 region of young and old male rats as they performed a spatial eye-blink conditioning task across 31 d. Although mean gamma frequency was similar in both groups, gamma frequency increased with running speed at a slower rate in old animals. By contrast, theta frequencies scaled with speed similarly in both groups but were lower across speeds in old animals. Although these frequencies scaled equally well with deceleration and speed, acceleration was less correlated with gamma frequency in both age groups. Additionally, spike phase-locking to gamma, but not theta, was greater in older animals. Finally, aged rats had reduced within-field firing rates but greater spatial information per spike within the field. These data support a strong relationship between locomotor behavior and local-field potential activity and suggest that age significantly affects this relationship. Furthermore, observed changes in CA1 place cell firing rates and information content lend support to the hypothesis that age may result in more general and context-invariant hippocampal representations over more detailed information. These results may explain the observation that older adults tend to recall the gist of an experience rather than the details.SIGNIFICANCE STATEMENT Hippocampal oscillations and place cell activity are sensitive to sensorimotor input generated from active locomotion, yet studies of aged hippocampal function often do not account for this. By considering locomotion and spatial location, we identify novel age-associated differences in the scaling of oscillatory activity with speed, spike-field coherence, spatial information content, and within-field firing rates of CA1 place cells. These results indicate that age has an impact on the relationship between locomotion and hippocampal oscillatory activity, perhaps indicative of alterations to afferent input. These data also support the hypothesis that aged hippocampal place cells, compared with young, may more often represent more general spatial information. If true, these results may help explain why older humans tend to recall less specific and more gist-like information.

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

Many hippocampal CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially tuned, temporally diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multicompartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared with somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in the closed state, which comprises the available pool. PKC activator phorbol-dibutyrate, known to reduce NaV long-term inactivation, removed spike amplitude attenuation in vitro more visibly in dendrites and greatly reduced adaptation, consistent with our hypothesized mechanism. Intracellular application of a peptide inducing long-term NaV inactivation elicited spike amplitude attenuation during spike trains in the soma and greatly enhanced adaptation. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is a key mechanism of adaptation in CA1 pyramidal cells.SIGNIFICANCE STATEMENT The hippocampus plays an important role in certain types of memory, in part through context-specific firing of "place cells"; these cells were first identified in rodents as being particularly active when an animal is in a specific location in an environment, called the place field of that neuron. In this in vitro/in silico study, we found that long-term inactivation of sodium channels causes adaptation in the firing rate that could potentially skew the firing of CA1 hippocampal pyramidal neurons earlier within a place field. A computational model of the sodium channel revealed differential regulation of spike frequency and amplitude by long-term inactivation, which may be a general mechanism for spike frequency adaptation in the CNS.

Toward the biological model of the hippocampus as the successor representation agent

The hippocampus is an essential brain region for spatial memory and learning. Recently, a theoretical model of the hippocampus based on temporal difference (TD) learning has been published. Inspired by the successor representation (SR) learning algorithms, which decompose value function of TD learning into reward and state transition, they argued that the rate of firing of CA1 place cells in the hippocampus represents the probability of state transition. This theory, called predictive map theory, claims that the hippocampus representing space learns the probability of transition from the current state to the future state. The neural correlates of expecting the future state are the firing rates of the CA1 place cells. This explanation is plausible for the results recorded in behavioral experiments, but it is lacking the neurobiological implications.Modifying the SR learning algorithm added biological implications to the predictive map theory. Similar with the simultaneous needs of information of the current and future state in the SR learning algorithm, the CA1 place cells receive two inputs from CA3 and entorhinal cortex. Mathematical transformation showed that the SR learning algorithm is equivalent to the heterosynaptic plasticity rule. The heterosynaptic plasticity phenomena in CA1 were discussed and compared with the modified SR update rule. This study attempted to interpret the TD algorithm as the neurobiological mechanism occurring in place learning, and to integrate the neuroscience and artificial intelligence approaches in the field.

Ripple band phase precession of place cell firing during replay

SummaryNeuronal “replay,” in which place cell firing during rest recapitulates recently experienced trajectories, is thought to mediate the transmission of information from hippocampus to neocortex, but the mechanism for this transmission is unknown. Here, we show that replay uses a phase code to represent spatial trajectories by the phase of firing relative to the 150- to 250-Hz “ripple” oscillations that accompany replay events. This phase code is analogous to the theta phase precession of place cell firing during navigation, in which place cells fire at progressively earlier phases of the 6- to 12-Hz theta oscillation as their place field is traversed, providing information about self-location that is additional to the rate code and a necessary precursor of replay. Thus, during replay, each ripple cycle contains a “forward sweep” of decoded locations along the recapitulated trajectory. Our results indicate a novel encoding of trajectory information during replay and implicates phase coding as a general mechanism by which the hippocampus transmits experienced and replayed sequential information to downstream targets.

Experience-dependent contextual codes in the hippocampus.

The hippocampus contains neural representations capable of supporting declarative memory. Hippocampal place cells are one such representation, firing in one or few locations in a given environment. Between environments, place cell firing fields remap (turning on/off or moving to a new location) to provide a population-wide code for distinct contexts. However, the manner by which contextual features combine to drive hippocampal remapping remains a matter of debate. Using large-scale in vivo two-photon intracellular calcium recordings in mice during virtual navigation, we show that remapping in the hippocampal region CA1 is driven by prior experience regarding the frequency of certain contexts and that remapping approximates an optimal estimate of the identity of the current context. A simple associative-learning mechanism reproduces these results. Together, our findings demonstrate that place cell remapping allows an animal to simultaneously identify its physical location and optimally estimate the identity of the environment.