Bidirectional regulation of social memory by two distinct types of GABAergic neurons in the lateral septum

Humans and animals memorize and recognize familiar conspecifics during social interactions, known as social memory. While the hippocampus is crucial for social memory, the dynamic regulation of social memory remains unclear. Here, using male mice, we identified two molecularly distinct subpopulations of GABAergic neurons in the mouse lateral septum (LS) expressing somatostatin (SST) and calbindin 1 (CB), respectively, with complementary distribution patterns. Activation of SST+ neurons enhances social memory acquisition, whereas activation of CB+ neurons inhibits it. Optogenetic manipulation of SST+ neurons regulates theta oscillations, correlating with their impact on social memory. SST+-dLS neurons and CB+-vLS neurons preferentially receive stronger excitatory inputs from the dorsal (vCA1d) and ventral (vCA1v) parts of vCA1, respectively. Functionally, the vCA1d→SST+-dLS→lateral hypothalamic area (LHA) circuit promotes social memory acquisition, whereas the vCA1v→CB+-vLS→anterior hypothalamic nucleus (AHN) pathway suppresses it. This study uncovers two parallel neural circuits underpinning the dynamic regulation of social memory in male mice.