Hippocampal Ripple Coordinates Retrosplenial Inhibitory Neurons during Slow-Wave Sleep

Summary: The hippocampus and retrosplenial cortex (RSC) play indispensable roles in memory formation, and importantly, a hippocampal oscillation known as ripple is key to consolidation of new memories. However, it remains unclear how the hippocampus and RSC communicate and the role of ripple oscillation in coordinating the activity between these two brain regions. Here, we record from the dorsal hippocampus and RSC simultaneously in freely behaving mice during sleep and reveal that the RSC displays a pre-ripple activation associated with slow and fast oscillations. Immediately after ripples, a subpopulation of RSC putative inhibitory neurons increases firing activity, while most RSC putative excitatory neurons decrease activity. Consistently, optogenetic stimulation of this hippocampus-RSC pathway activates and suppresses RSC putative inhibitory and excitatory neurons, respectively. These results suggest that the dorsal hippocampus mainly inhibits RSC activity via its direct innervation of RSC inhibitory neurons, which overshadows the RSC in supporting learning and memory functions. : Converging evidence suggests that hippocampal ripple oscillations and their interaction with the neocortex are critical for memory consolidation. By combining electrophysiology and optogenetic techniques in freely behaving mice, Opalka et al. provide direct evidence that hippocampal ripples communicate with retrosplenial cortex (RSC) interneurons and inhibit RSC population activity during sleep-associated memory consolidation. Keywords: hippocampus, retrosplenial cortex, sharp-wave ripple, neural oscillation, memory consolidation, memory formation, slow-wave sleep, optogenetic stimulation, in vivo recording, neural ensemble