Rate Remapping Research Articles

Adult-born granule cells facilitate remapping of spatial and non-spatial representations in the dentate gyrus

Adult-born granule cells (abGCs) have been implicated in memory discrimination through a neural computation known as pattern separation. Here, using invivo Ca2+ imaging, we examined how chronic ablation or acute chemogenetic silencing of abGCs affects the activity of mature granule cells (mGCs). In both cases, we observed altered remapping of mGCs. Rather than broadly modulating the activity of all mGCs, abGCs promote the remapping of place cells' firing fields while increasing rate remapping of mGCs that represent sensory cues. In turn, these remapping deficits are associated with behavioral impairments in animals' ability to correctly identify new goal locations. Thus, abGCs facilitate pattern separation through the formation of non-overlapping representations for identical sensory cues encountered in different locations. In the absence of abGCs, the dentate gyrus shifts to a state that is dominated by cue information, a situation that is consistent with the overgeneralization often observed in anxiety or age-related disorders.

Burst activity plays no role in the field-to-field variability and rate remapping of grid cells.

Grid cells in rodent medial entorhinal cortex are thought to play a key role for spatial navigation. When the animal is freely moving in an open arena the firing fields of each grid cell tend to form a highly regular, hexagonal lattice spanning the environment. However, firing rates vary from field to field and change under contextual modifications, whereas the field locations shift at most by a small amount under such "rate remapping." The observed differences in firing rate could reflect overall activity changes or changes in the detailed spike-train statistics. As these two alternatives imply distinct neural coding schemes, we investigated whether temporal firing patterns vary from field to field and whether they change under rate remapping. Focusing on short time scales, we found that the proportion of bursts compared to all discharge events is similar in all firing fields of a given grid cell and does not change under rate remapping. For each cell, mean firing rates with bursts are proportional to mean firing rates without bursts. However, this ratio varies across cells. Additionally, we looked at how rate remapping relates to entorhinal theta-frequency oscillations. Theta-phase coding was preserved despite firing-rate changes from rate remapping but we did not observe differences between the first and second half of the theta cycle, as had been reported for CA1. Our results indicate that both, the heterogeneity between firing fields and rate remapping, are not due to altered firing patterns on short time scales but reflect location-specific changes at the firing-rate level.

Hippocampal neurons represent events as transferable units of experience.

The brain codes continuous spatial, temporal and sensory changes in daily experience. Recent studies suggest that the brain also tracks experience as segmented subdivisions (events), but the neural basis for encoding events remains unclear. Here, we designed a maze for mice, composed of four materially indistinguishable lap events, and identify hippocampal CA1 neurons whose activity are modulated not only by spatial location but also lap number. These 'event-specific rate remapping' (ESR) cells remain lap-specific even when the maze length is unpredictably altered within trials, which suggests that ESR cells treat lap events as fundamental units. The activity pattern of ESR cells is reused to represent lap events when the maze geometry is altered from square to circle, which suggests that it helps transfer knowledge between experiences. ESR activity is separately manipulable from spatial activity, and may therefore constitute an independent hippocampal code: an 'event code' dedicated to organizing experience by events as discrete and transferable units.

Temporal coding and rate remapping: Representation of nonspatial information in the hippocampus.

Hippocampal place cells represent nonspatial information through a process called rate remapping, which involves a change in the firing rate of a place cell without changes in its spatial specificity. However, many hippocampal phenomena occur on very short time scales over which long-term average firing rates are not an appropriate description of activity. To understand how rate remapping relates to fine-scale temporal firing phenomena, we asked how rate remapping affected burst firing and trial-to-trial spike count variability. In addition, we looked at how rate remapping relates to the theta-frequency oscillations of the hippocampus, which are thought to temporally organize firing on time scales faster than 100 ms. We found that theta phase coding was preserved through changes in firing rate due to rate remapping. Interestingly, rate remapping in CA1 in response to task demands preferentially occurred during the first half of the theta cycle. The other half of the theta cycle contained preferential expression of phase precession, a phenomenon associated with place cell sequences, in agreement with previous results. This difference of place cell coding during different halves of the theta cycle supports recent theoretical suggestions that different processes occur during the two halves of the theta cycle. The differentiation between the halves of the theta cycle was not clear in recordings from CA3 during rate remapping induced by task-irrelevant sensory changes. These findings provide new insight into the way that temporal coding is utilized in the hippocampus and how rate remapping is expressed through that temporal code.

Differential Rate Coding of Visual Context in the Subiculum and Hippocampus

Discharge rates of place cells in the hippocampus are modulated by changes in the sensory environment. Such rate remapping may underlie the neural code responsible for remembering different events that take place in the same location, but it is unknown if rate remapping is a code unique to the hippocampus. Recordings from neurons in the rat subiculum and CA1 during a visual contextual me mory task showed that contextual rate remapping occurred more strongly in the subiculum than the CA1 during recognition of a familiar visual context. However, increases in contextual ambiguity led to a decrease in both performance and context-specific firing in the CA1; by contrast, no such ambiguity-related neural correlate was found in the subiculum. Our findings suggest that rate remapping occurs globally in the brain, but recognizing an altered environment may be a unique function of the hippocampus.

Place and Grid Cells in a Loop: Implications for Memory Function and Spatial Coding.

Place cells in the hippocampus and grid cells in the medial entorhinal cortex have different codes for space. However, how one code relates to the other is ill understood. Based on the anatomy of the entorhinal-hippocampal circuitry, we constructed a model of place and grid cells organized in a loop to investigate their mutual influence in the establishment of their codes for space. Using computer simulations, we first replicated experiments in rats that measured place and grid cell activity in different environments, and then assessed which features of the model account for different phenomena observed in neurophysiological data, such as pattern completion and pattern separation, global and rate remapping of place cells, and realignment of grid cells. We found that (1) the interaction between grid and place cells converges quickly; (2) the spatial code of place cells does not require, but is altered by, grid cell input; (3) plasticity in sensory inputs to place cells is key for pattern completion but not pattern separation; (4) grid realignment can be explained in terms of place cell remapping as opposed to the other way around; (5) the switch between global and rate remapping is self-organized; and (6) grid cell input to place cells helps stabilize their code under noisy and/or inconsistent sensory input. We conclude that the hippocampus-entorhinal circuit uses the mutual interaction of place and grid cells to encode the surrounding environment and propose a theory on how such interdependence underlies the formation and use of the cognitive map.SIGNIFICANCE STATEMENT The mammalian brain implements a positional system with two key pieces: place and grid cells. To gain insight into the dynamics of place and grid cell interaction, we built a computational model with the two cell types organized in a loop. The proposed model accounts for differences in how place and grid cells represent different environments and provides a new interpretation in which place and grid cells mutually interact to form a coupled code for space.

Reactivation of Rate Remapping in CA3.

The hippocampus is thought to contribute to episodic memory by creating, storing, and reactivating patterns that are unique to each experience, including different experiences that happen at the same location. Hippocampus can combine spatial and contextual/episodic information using a dual coding scheme known as "global" and "rate" remapping. Global remapping selects which set of neurons can activate at a given location. Rate remapping readjusts the firing rates of this set depending on current experience, thus expressing experience-unique patterns at each location. But can the experience-unique component be retrieved spontaneously? Whereas reactivation of recent, spatially selective patterns in hippocampus is well established, it is never perfect, raising the issue of whether the experiential component might be absent. This question is key to the hypothesis that hippocampus can assist memory consolidation by reactivating and broadcasting experience-specific "index codes" to neocortex. In CA3, global remapping exhibits attractor-like dynamics, whereas rate remapping apparently does not, leading to the hypothesis that only the former can be retrieved associatively and casting doubt on the general consolidation hypothesis. Therefore, we studied whether the rate component is reactivated spontaneously during sleep. We conducted neural ensemble recordings from CA3 while rats ran on a circular track in different directions (in different sessions) and while they slept. It was shown previously that the two directions of running result in strong rate remapping. During sleep, the most recent rate distribution was reactivated preferentially. Therefore, CA3 can retrieve patterns spontaneously that are unique to both the location and the content of recent experience. The hippocampus is required for memory of events and their spatial contexts. The primary correlate of hippocampal activity is location in space, but multiple memories can occur in the same location. To be useful for distinguishing these memories, the hippocampus must be able, not only to express, but also to retrieve both spatial and nonspatial information about events. Whether it can retrieve nonspatial information has been challenged recently. We exposed rats to two different experiences (running in different directions) in the same locations and showed that even the nonspatial components of hippocampal cell firing are reactivated spontaneously during sleep, supporting the conclusion that both types of information about a recent experience can be retrieved.

Asymmetry of Neuronal Combinatorial Codes Arises from Minimizing Synaptic Weight Change

Synaptic change is a costly resource, particularly for brain structures that have a high demand of synaptic plasticity. For example, building memories of object positions requires efficient use of plasticity resources since objects can easily change their location in space and yet we can memorize object locations. But how should a neural circuit ideally be set up to integrate two input streams (object location and identity) in case the overall synaptic changes should be minimized during ongoing learning? This letter provides a theoretical framework on how the two input pathways should ideally be specified. Generally the model predicts that the information-rich pathway should be plastic and encoded sparsely, whereas the pathway conveying less information should be encoded densely and undergo learning only if a neuronal representation of a novel object has to be established. As an example, we consider hippocampal area CA1, which combines place and object information. The model thereby provides a normative account of hippocampal rate remapping, that is, modulations of place field activity by changes of local cues. It may as well be applicable to other brain areas (such as neocortical layer V) that learn combinatorial codes from multiple input streams.

Activity-dependent plasticity of hippocampal place maps.

Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping.

Reliability and Precision Are Optimal for Non-Uniform Distributions of Presynaptic Release Probability

Most conceptual and computational models assume that synaptic transmission is reliable, a simplification rarely substantiated by data. The functional consequences of the recruitment of high and low initial release probability synapses on the reliability and precision of their postsynaptic targets are studied in a multi-compartmental model of a hippocampal CA1 pyramidal cell. We show that changes in the firing rate of CA3 afferent inputs (rate remapping) are not reflected in the firing rate of the CA1 cell but in the reliability and precise timing of some of its action potentials, suggesting that a signature of remapping may be found in the precise spike timing of CA1. Our results suggest that about half of the action potentials produced by a CA1 cell can potentially carry reliable information in their precise timing with about 25 ms precision, a time scale on the order of the gamma cycle. We show further that reliable events were primarily elicited by CA3 synapses in a state of low probability of release. Overall, our results suggest that the non-uniform distribution of initial release probabilities observed experimentally achieves an optimum yielding simultaneously high precision and high reliability, and allows large populations of CA3 synapses to contribute to the production of reliable CA1 spiking events.

Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze.

Hippocampal place responses can be prospectively or retrospectively modulated by the animal's future or prior trajectory. Two main hypotheses explain this. The "multiple-map hypothesis" switches between different maps for different trajectories (rate remapping). In contrast, in the "buffer hypothesis," the hippocampus encodes an ongoing representation that includes the recent past and/or the impending future choice. This study examines the distribution of prospective and retrospective responses distributed along a common path in a continuous T-maze (providing all four combinations of provenance and destination) during a visual discrimination task. The multiple-map hypothesis predicts either uniform distributions or concerted shifts about a task-decision relevant point, whereas the buffer hypothesis predicts a time-limited overexpression around choice points (with retrospective responses after the central arm entry point and prospective responses nearer its exit). Here bilateral recordings in the dorsal CA1 region of the rat hippocampus show that retrospective responses were twice as prevalent as prospective responses. Furthermore, retrospective and prospective modulations have distinct spatial distributions, with retrospective primarily in the first two-thirds of the central arm and prospective restricted to the last third. To test for possible trial-by-trial remapping in relation to the two-thirds transition point, data from the first and second halves of the sessions were compared. Backward drift of path-modulated activity was significant only for retrospective, but not prospective, fields. Thus, these data are more consistent with the buffer hypothesis. Retrospective and prospective modulation would then participate in a single hippocampal representation of spatial and behavioral context.

Place cell rate remapping by CA3 recurrent collaterals.

Episodic-like memory is thought to be supported by attractor dynamics in the hippocampus. A possible neural substrate for this memory mechanism is rate remapping, in which the spatial map of place cells encodes contextual information through firing rate variability. To test whether memories are stored as multimodal attractors in populations of place cells, recent experiments morphed one familiar context into another while observing the responses of CA3 cell ensembles. Average population activity in CA3 was reported to transition gradually rather than abruptly from one familiar context to the next, suggesting a lack of attractive forces associated with the two stored representations. On the other hand, individual CA3 cells showed a mix of gradual and abrupt transitions at different points along the morph sequence, and some displayed hysteresis which is a signature of attractor dynamics. To understand whether these seemingly conflicting results are commensurate with attractor network theory, we developed a neural network model of the CA3 with attractors for both position and discrete contexts. We found that for memories stored in overlapping neural ensembles within a single spatial map, position-dependent context attractors made transitions at different points along the morph sequence. Smooth transition curves arose from averaging across the population, while a heterogeneous set of responses was observed on the single unit level. In contrast, orthogonal memories led to abrupt and coherent transitions on both population and single unit levels as experimentally observed when remapping between two independent spatial maps. Strong recurrent feedback entailed a hysteretic effect on the network which diminished with the amount of overlap in the stored memories. These results suggest that context-dependent memory can be supported by overlapping local attractors within a spatial map of CA3 place cells. Similar mechanisms for context-dependent memory may also be found in other regions of the cerebral cortex.

Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex

In the hippocampus, spatial and non-spatial parameters may be represented by a dual coding scheme, in which coordinates in space are expressed by the collective firing locations of place cells and the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Although the spatial signal may reflect input from medial entorhinal cortex, the sources of the variations in firing rate have not been identified. We found that rate variations in rat CA3 place cells depended on inputs from the lateral entorhinal cortex (LEC). Hippocampal rate remapping, induced by changing the shape or the color configuration of the environment, was impaired by lesions in those parts of the ipsilateral LEC that provided the densest input to the hippocampal recording position. Rate remapping was not observed in LEC itself. The findings suggest that LEC inputs are important for efficient rate coding in the hippocampus.

Hippocampal Place Cells Can Encode Multiple Trial-Dependent Features through Rate Remapping

The activity of hippocampal pyramidal cells reflects both the current position of the animal and information related to its current behavior. Here we investigated whether single hippocampal neurons can encode several independent features defining trials during a memory task. We also tested whether task-related information is represented by partial remapping of the place cell population or, instead, via firing rate modulation of spatially stable place cells. To address these two questions, the activity of hippocampal neurons was recorded in rats performing a conditional discrimination task on a modified T-maze in which the identity of a food reward guided behavior. When the rat was on the central arm of the maze, the firing rate of pyramidal cells changed depending on two independent factors: (1) the identity of the food reward given to the animal and (2) the previous location of the animal on the maze. Importantly, some pyramidal cells encoded information relative to both factors. This trial-type specific and retrospective coding did not interfere with the spatial representation of the maze: hippocampal cells had stable place fields and their theta-phase precession profiles were unaltered during the task, indicating that trial-related information was encoded via rate remapping. During error trials, encoding of both trial-related information and spatial location was impaired. Finally, we found that pyramidal cells also encode trial-related information via rate remapping during the continuous version of the rewarded alternation task without delays. These results suggest that hippocampal neurons can encode several task-related cognitive aspects via rate remapping.

Reorganization of spatial maps in the hippocampal circuit

It is known that the hippocampus plays a central role in the storage and in the retrieval of episodic memories. In particular the study of population dynamics in hippocampal place cells has emerged as one of the most powerful tools for understanding the encoding, storage and retrieval of episodic memories. Place cells are hippocampal neurons whose discharge is strongly related to a rat location in its environment. The existence of place cells has led to the proposal that they are part of an integrated neural system, which involves also parahippocampal regions, dedicated to spatial navigation and memory. Accumulating evidence suggests that environments are generally represented in hippocampal cells as a collection of manifolds associated to real space. Observed phenomena like global remapping and rate remapping can give us insights on the nature of these maps and on the attractor dynamics that governs their storage and retrieval. As the representation of the same environment is differently expressed in hippocampal subregions it becomes important to understand the function of the sequential transmission through the DG, CA3 and CA1. Indeed, while the particular autoassociative operations are ascribed mainly to the recurrent CA3 network, the role of CA1 and of the CA3-to-CA1 connections is not clear. We address these questions, restricted to Schaffer Collaterals connections for clarity, within a simplified mathematical network model. The model network simulates the storage on CA3 of one or more spatial representations, and their transfer to CA1. We quantify through information measures the ability of Schaffer Collaterals connections to reproduce the retrieved representation in CA1 and with which modifications, after a training phase in which they are modified through model Hebbian plasticity, or else after having been structured top-down. In particular we analyzed the way in which correlated or uncorrelated CA3 maps are actually represented in CA1. We find that in the CA1 maps there is a “smoother” representation of space, and that there is substantial difference in the way information is expressed. Finally, we find that even networks of considerable size can only approximate the idealized notion of a 2D quasi-continuous dynamical attractor.

Hippocampal population dynamics underlying memory trace activation in a tactile classification task

Hippocampal neuronal ensemble activity appears to play an important role in establishment of spatial and non-spatial episodic memories [1] and [2]. In particular, CA1 region of the hippocampus is well known to be a crucial site for processing associative memories which typically contain information about what, where, and when major behavioral events occurred [3]. In simple navigation tasks, it was shown that different spatial information can unfold in time either by complete reorganization of hippocampal place code in which both place and rate of firing take statistically independent values (global remapping, [4] and[5]) or instead, through minor modulation of firing rates in a same neural assembly (rate remapping, [4] and [5]). But to date, there is no evidence how CA1 ensembles remap to code different phases of a sensory, in particular tactile, memory task, at population level. Previously, it was shown how “single” cells in CA1 adapt an independent coding to represent tactile and reward location information [6]. This finding indicates that hippocampal neurons did not encode textured stimuli as physical objects along specific dimensions (e.g. coarseness), but as meaningful events in conjunction with the location in which they appeared. Moreover, the coding properties of neurons did not “follow” them across contexts. Here, we further analyzed population dynamics underlying this independence coding and explore both quantitative and qualitative differences between information content of single unit activities versus population vector. On each trial the rat touched a textured plate with its whiskers, and then turned towards the Left or Right water spout. Firstly, we measured the degree of rate-remapping, due to task-induced changes in population activity. The kolmogorov-smirnov distance between the empirical firing rate distribution of each single cell, collapsed in time and trial, and different null hypotheses, based on different assumptions on global remapping was computed. We also computed the correlation between pairs of population vectors taken from different times of each trial. These measures are independent of the relative magnitude of firing. Comparing the distributions of correlation values for entire set of population vectors between two trials, or two behaviorally different phases of each trial, provides an estimate of how much the ensemble code changes. When the rats experienced different phases of the task, however, the hippocampus encoded these changes robustly by changing the values of the components of the population vectors, without much, if any, change in the ensemble of recruited cells. Secondly, to see how presence of noise correlations may enhance coding property of the population, the performance of a non-linear classifier trained on few informative “single” cells was contrasted with a classifier trained on a) the complete set of cells and b) the principle components of the cell assembly. Thirdly, we applied trajectory-based activity classification of neural responses using Hidden Markov models, to segment the complete recording into a sequence of a few statistically discriminated hidden states, each correlated with different behavioral condition.

The Mechanism of Rate Remapping in the Dentate Gyrus

Rate remapping is a recently revealed neural code in which sensory information modulates the firing rate of hippocampal place cells. The mechanism underlying rate remapping is unknown. Its characteristic modulation, however, must arise from the interaction of the two major inputs to the hippocampus, the medial entorhinal cortex (MEC), in which grid cells represent the spatial position of the rat, and the lateral entorhinal cortex (LEC), in which cells represent the sensory properties of the environment. We have used computational methods to elucidate the mechanism by which this interaction produces rate remapping. We show that the convergence of LEC and MEC inputs, in conjunction with a competitive network process mediated by feedback inhibition, can account quantitatively for this phenomenon. The same principle accounts for why different place fields of the same cell vary independently as sensory information is altered. Our results show that rate remapping can be explained in terms of known mechanisms.

Rate Remapping: When the Code Goes beyond Space

Rate remapping is a conjunctive code that potentially enables hippocampal place cells to jointly represent spatial and nonspatial information. In this issue of Neuron, Rennó-Costa et al. introduce a theoretical model wherein the convergence of the medial and lateral entorhinal excitatory inputs, combined with local inhibition, explains hippocampal rate remapping.

Modeling Rate Remapping in Dentate Gyrus

Event Abstract Back to Event Modeling Rate Remapping in Dentate Gyrus Bailu Si1* and Alessandro Treves1, 2 1 SISSA, Cognitive Neuroscience Sector, Italy 2 Center for the Biology of Memory, NTNU, Kavli Institute for Systems Neuroscience, Norway Hypothesized to be the neural basis for pattern separation, dentate gyrus (DG) has been proposed to separate similar cortical inputs into sparse representations before the input patterns are stored in memory in Hippocampus. This hypothesis has recently been confirmed experimentally by Leutgeb and colleagues. They showed that when the shape of the recording environment morphs, the multiple firing fields of DG granule cells change progressively and independently, i.e. rate remap, and that the activity patterns in similar environments are decorrelated as compared with the inputs. Here we present a simple non-dynamical model where DG units are described by a threshold-linear transfer function, and where each DG unit receives both contextual-spatial modulated inputs from 1,000 medial entorhinal cortex (mEC) model grid units and contextual but non-spatial input from lateral entorhinal cortex (lEC) model units. The feed-forward weights from mEC units to DG units are updated according to a Hebbian rule as the virtual rodent explores in the two extreme environments. Through competitive Hebbian learning, DG place fields emerge. In addition the context modulation from the EC pathway makes the DG response depend on the environment when the environment morphs. As a result, when the network is tested in the morphing environment after training, the activity patterns of DG units show rate remapping. Conference: Neuroinformatics 2009, Pilsen, Czechia, 6 Sep - 8 Sep, 2009. Presentation Type: Poster Presentation Topic: Computational neuroscience Citation: Si B and Treves A (2019). Modeling Rate Remapping in Dentate Gyrus. Front. Neuroinform. Conference Abstract: Neuroinformatics 2009. doi: 10.3389/conf.neuro.11.2009.08.094 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 May 2009; Published Online: 09 May 2019. * Correspondence: Bailu Si, SISSA, Cognitive Neuroscience Sector, Trieste, Italy, bailusi@sissa.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bailu Si Alessandro Treves Google Bailu Si Alessandro Treves Google Scholar Bailu Si Alessandro Treves PubMed Bailu Si Alessandro Treves Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Dentate Gyrus Rate Remapping Can Be Modeled by Context Modulation in Entorhinal Cortex

Dentate Gyrus Rate Remapping Can Be Modeled by Context Modulation in Entorhinal Cortex