SummaryThe ability to reinstate neuronal assemblies representing mnemonic information is thought to require their consolidation through offline reactivation during sleep/rest. To test this, we detected cell assembly patterns formed by repeated neuronal co-activations in the mouse hippocampus during exploration of spatial environments. We found that the reinstatement of assembly patterns representing a novel, but not a familiar, environment correlated with their offline reactivation and was impaired by closed-loop optogenetic disruption of sharp wave-ripple oscillations. Moreover, we discovered that reactivation was only required for the reinstatement of assembly patterns whose expression was gradually strengthened during encoding of a novel place. The context-dependent reinstatement of assembly patterns whose expression did not gain in strength beyond the first few minutes of spatial encoding was not dependent on reactivation. This demonstrates that the hippocampus can hold concurrent representations of space that markedly differ in their encoding dynamics and their dependence on offline reactivation for consolidation.Video Abstract

The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places increased relative to the sleep session before exploration. This cofiring increase depended on the number of times that cells fired together with short latencies (<50 ms) during exploration, and was strongest between cells representing the most visited places. This is indicative of a Hebbian learning rule in which changes in firing associations between cells are determined by the number of waking coincident firing events. In contrast, cells encoding different locations reduced their cofiring in proportion to the number of times that they fired independently. Together these data indicate that reactivated patterns are shaped by both positive and negative changes in cofiring, which are determined by recent behavior.

Temporal coding is a means of representing information by the time, as opposed to the rate, at which neurons fire. Evidence of temporal coding in the hippocampus comes from place cells, whose spike times relative to theta oscillations reflect a rat's position while running along stereotyped trajectories. This arises from the backwards shift in cell firing relative to local theta oscillations (phase precession). Here we demonstrate phase precession during place-field crossings in an open-field foraging task. This produced spike sequences in each theta cycle that disambiguate the rat's trajectory through two-dimensional space and can be used to predict movement direction. Furthermore, position and movement direction were maximally predicted from firing in the early and late portions of the theta cycle, respectively. This represents the first direct evidence of a combined representation of position, trajectory and heading in the hippocampus, organized on a fine temporal scale by theta oscillations.