Retrosplenial neuronal subpopulations and inputs

Sleep, which occupies nearly a third of our lives, is essential for converting experiences into lasting memories through a process known as memory consolidation. During consolidation, new information is reorganized and gradually integrated into pre-existing cortical neural networks. A key player in this process is the delta rhythm (0.5-4 Hz), which dominates the cortex during slow-wave sleep (SWS), synchronizing activity across brain regions to facilitate information flow. This cortical delta rhythm features alternating Up and Down states, characterized by periods of high neuronal activity and almost complete neuronal silence, respectively. Emerging evidence suggests that both Up and Down states are crucial for information exchange associated with the consolidation process. One brain region poised to play a pivotal role in this process is the retrosplenial cortex (RSC), which is extensively connected with memory-associated regions. However, it remains unclear how RSC neuronal populations engage in delta wave-associated consolidation processes. Here, we employed multi-channel in vivo electrophysiology to study RSC neuronal activity in freely behaving mice during natural SWS. We discovered a discrete assembly of putative excitatory RSC neurons (~20%) that initiated firing at SWS Down states and reached maximal activity when Down states transitioned to Up states. Therefore, we termed these RSC neurons the Down-to-Up transition Assembly (DUA), and the remaining RSC excitatory neurons as non-DUA. DUA neurons fired at higher rates, exhibited larger cell bodies, and lacked monosynaptic connectivity with nearby RSC neurons, in contrast to their non-DUA counterparts. Subsequently, we investigated RSC neuronal activity during a contextual fear conditioning memory paradigm. Both DUA and non-DUA neurons displayed heightened firing during post-training sleep compared to pre-training sleep, indicating their likely roles in memory consolidation. Lastly, we utilized optogenetics combined with electrophysiology to reveal differential innervation of RSC neuronal populations by memory-associated inputs. This was further corroborated by our findings of coordinated activity between hippocampal neurons and RSC interneurons. These findings unveil a previously unrecognized neural assembly that activates at SWS Down-to-Up transition, shedding light on the intricate mechanisms underlying memory consolidation. A better understanding of how new information is integrated into brain networks during sleep can inform innovative strategies to enhance memory and combat cognitive disorders.