Generative replay across hippocampal-neocortical circuits

To make flexible decisions, the brain needs to infer relationships between events that were not directly experienced together. During sharp-wave ripple (SWR) events in periods of rest/sleep, spiking activity in the hippocampus appears to support this process by co-activating memories of discrete cues and events. However, it remains unclear whether this "generative replay" also occurs in other brain regions, to update beliefs across the brain. To address this question, here we combine multi-unit electrophysiology and calcium imaging in freely moving mice performing an inference task. We reveal evidence for generative replay in sensory neocortex, where spiking sequences in V1 encode relationships that were never directly experienced. This activity is predicted by preceding information content in hippocampus, suggesting the hippocampus provides a teaching signal to reorganize neocortical representations. Generative replay in hippocampus may therefore endow neocortex with capacity to build a hierarchical generative model that supports flexible and adaptive behaviour.