Hippocampal Offline Reactivation Consolidates Recently Formed Cell Assembly Patterns during Sharp Wave-Ripples

The 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. [Display omitted] •Multi-neuron co-activations form space-coding assembly patterns in the hippocampus•Offline reactivation of new assembly patterns correlates with future reinstatement•SWR silencing impairs consolidation of patterns of a novel, but not a familiar, place•“Early stabilized” patterns representing a novel place do not require reactivation van de Ven et al. identify hippocampal cell assembly patterns formed by repeated multi-neuron co-activations and show that only those patterns that represent a novel place and that were gradually strengthened during their first expression require SWR reactivation for their context-dependent reinstatement.