Inhibitory inputs from hippocampal CA1 to retrosplenial agranular cortex gate social behavior

ABSTRACT Retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity observed in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASD). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. This work reveals that the neural activity of retrosplenial agranular cortex (RSA), a subregion of retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. The up-down phase of RSA neurons is crucial for normal social behaviors. PV-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input could rescue social behavior defects in an ASD mouse model. This work suggests a neural mechanism for salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.