Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition.

Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and retrieval/expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we used an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory retrieval and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

Hippocampal Ripple Coordinates Retrosplenial Inhibitory Neurons during Slow-Wave Sleep.

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.