Cell assemblies, sequences and temporal coding in the hippocampus
Introduction
Information processing in the brain relies on interconnected networks of neurons. Single neurons perform information encoding by both rate changes within and across receptive fields and temporal coding by phase preference and phase precession within their receptive fields [1,2]. Changes in coordinated firing across individual neurons as well as selective changes in timing and sequential order across neurons induced by novel experiences have collectively been known as ensemble temporal coding [3,4]. However, first, genuine neuronal ensemble temporal coding can be hard to distinguish from independent or correlated changes in firing rates of populations of neurons, which can often give the appearance of increased coordination and sequential organization of the neurons [5,6]. Second, temporal coding would need to be distinguished from the default neuronal organization in Hebbian cell assemblies and into temporal sequences of firing also known as Hebbian phase sequence that both operate at (tens of) millisecond timescales [7,8]. Third, as the default neuronal activity is temporally organized into coordinated firing within cell assemblies and sequential firing within and predominantly across cell assemblies even during slow-wave sleep, when the brain is fairly disconnected from the external world, the coding aspect of temporal coding will need to be further refined.
Here, we propose that specific changes in temporal organization of spontaneous neuronal ensemble activity from the sleep preceding to the one following a novel experience can be used to infer and validate the changes associated with coding during the experience and be considered a form of network learning and representation by temporal coding. Using an overview of data published in the recent years, we further propose that this temporal coding relies primarily on subtle and selective changes in coordinated firing within individual cell assemblies already part of a temporal sequence, in line with a predictive internal model. Finally, we describe the changes in the microstructure of neuronal firing within cell assemblies as the basis for the ensemble temporal coding using data on spatial coding in the rodent hippocampus.
Section snippets
State-dependent temporal sequences of firing: theta sequences, replay, and preplay
The rodent hippocampus has proved to be an excellent and productive model system in which to study the basic principles of internally generated representations in the brain, in the form of episodic memories [9] and ‘cognitive maps’ [1]. In the adult rodent, in addition to individual place cells that represent specific spatial locations along an animal trajectory at ‘clock time’ scale during theta oscillations, ensembles of pyramidal cells in the hippocampus are organized into temporo-spatial
Theta sequences and the plasticity in temporal sequences during sleep
Given the complex multisensory, associative nature of hippocampal activity and the existence of default temporally compressed sequences of firing during sleep, a convincing assessment of pure temporal coding of presumed sequential stimuli encountered during rodent navigation has remained difficult. The mnemonic features repeatedly demonstrated for the hippocampal formation have provided us with an opportunity to infer temporal encoding during navigation by decoding and evaluating the plastic
The character of replay plasticity: subtle, selective, cell-assembly coordination-based
The plasticity in decoded representations of previous navigational experience is generally detected by performing Bayesian decoding of neuronal activity during sleep. Several coding schemes combine to contribute to the decoded representations during sleep: rate coding, temporal sequence coding, and temporal coordination coding. Rate coding is primarily represented by changes in neuronal firing rates during the sleep after a navigational experience as a function of their firing rates during the
Microstructure of cell assembly activation and plasticity underlying temporal coding
Recent work has shown that interfering with cell assembly activation during offline epochs of neuronal activity during post encoding rest and sleep can affect learning and behavior performance of the animals [57,63••,64•]. This suggests that offline temporal coordination coding, which relies on cell assembly activation, could play a critical role in stabilization and consolidation of a recent memory. Conversely, increased neuronal participation and cell assembly activation by artificially
Conclusions
The relationship between cell assembly organization and temporal coding has traditionally been difficult to draw. This was in part because the fine temporal organization of neuronal activity in cell assemblies and temporal sequences in the hippocampus appears to follow temporal coding principles even during offline states like slow wave sleep when the brain is fairly disconnected from the external world [23,46,56]. Part of this functional organization represents default sequential activity of
Author contributions
G.D. conceived and wrote the manuscript.
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank all the members of the Dragoi lab for their contribution to the primary experimental research work that led to some of the findings included in this opinion. This work was supported by funding from the NINDS of the NIH under award number R01NS104917 and from NIMH of the NIH under award number R01MH121372 to G.D. The funding sources had no involvement in the content of this manuscript.
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