Abstract During states of behavioral quiescence, neurons in the hippocampus replay sequences of spiking activity experienced in earlier behavioral episodes. While such replay sequences are hypothesized to serve learning and memory by facilitating synaptic consolidation, their generative mechanisms remain poorly understood. Increasing evidence suggests that they might be generated internally, or at least strongly constrained by internal circuit dynamics. Recent work demonstrated that, across the forebrain, approximately 70% of neurons participate in a pattern of sequential spiking cascades during rest. Like hippocampal replay sequences, these brain-wide spiking cascades occur together with high-frequency hippocampal ripples and therefore may share a common generative mechanism. Here we systematically investigated the relationship between replay activity and sequential spiking cascades by analyzing a database of intracortical electrocortical recordings in mice. For neuronal subpopulations in the hippocampus and visual cortex, we assessed spiking sequences elicited during video viewing as well as potential replay events during subsequent periods of rest. We found that replay events were unique to hippocampal time-sensitive neurons and occurred together with spiking cascades throughout the forebrain. Furthermore, forward and time-reversed replay sequences were associated with different types of spiking cascades. Overall, these findings indicate that hippocampal replay events are generated and structured according to resting state circuit dynamics manifest across a large portion of the brain.

Self-generated brain-wide spiking cascades govern replay dynamics in the hippocampus