Coordinated Interactions between the Hippocampus and Retrosplenial Cortex in Spatial Memory

While a hippocampal-cortical dialogue is generally thought to mediate memory consolidation, which is crucial for engram function, how it works remains largely unknown. Here, we examined the interplay of neural signals from the retrosplenial cortex (RSC), a neocortical region, and from the hippocampus in memory consolidation by simultaneously recording sharp-wave ripples (SWRs) of dorsal hippocampal CA1 and neural signals of RSC in free-moving mice during the delayed spatial alternation task (DSAT) and subsequent sleep. Hippocampal-RSC coordination during SWRs was identified in nonrapid eye movement (NREM) sleep, reflecting neural reactivation of decision-making in the task, as shown by a peak reactivation strength within SWRs. Using modified generalized linear models (GLMs), we traced information flow through the RSC-CA1-RSC circuit around SWRs during sleep following DSAT. Our findings show that after spatial training, RSC excitatory neurons typically increase CA1 activity prior to hippocampal SWRs, potentially initiating hippocampal memory replay, while inhibitory neurons are activated by hippocampal outputs in post-SWRs. We further identified certain excitatory neurons in the RSC that encoded spatial information related to the DSAT. These neurons, classified as splitters and location-related cells, showed varied responses to hippocampal SWRs. Overall, our study highlights the complex dynamics between the RSC and hippocampal CA1 region during SWRs in NREM sleep, underscoring their critical interplay in spatial memory consolidation.