Hippocampal replay sequence governed by spontaneous brain-wide dynamics

Neurons in the hippocampus exhibit spontaneous spiking activity during rest that appears to recapitulate previously experienced events. While this replay activity is frequently linked to memory consolidation and learning, the underlying mechanisms are not well understood. Recent large-scale neural recordings in mice have demonstrated that resting-state spontaneous activity is expressed as quasi-periodic cascades of spiking activity that pervade the forebrain, with each cascade engaging a high proportion of recorded neurons. Hippocampal ripples are known to be coordinated with cortical dynamics; however, less is known about the occurrence of replay activity relative to other brain-wide spontaneous events. Here we analyzed responses across the mouse brain to multiple viewings of natural movies, as well as subsequent patterns of neural activity during rest. We found that hippocampal neurons showed time-selectivity, with individual neurons responding consistently during particular moments of the movie. During rest, the population of time-selective hippocampal neurons showed both forward and time-reversed replay activity that matched the sequence observed in the movie. Importantly, these replay events were strongly time-locked to brain-wide spiking cascades, with forward and time-reversed replay activity associated with distinct cascade types. Thus, intrinsic hippocampal replay activity is temporally structured according to large-scale spontaneous physiology affecting areas throughout the forebrain. These findings shed light on the coordination between hippocampal and cortical circuits thought to be critical for memory consolidation.