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 associal memory. While the hippocampus is crucial for social memory, the dynamic regulation social memory, particularly the negative regulation, remains unclear. Here, we identified two molecularly distinct subpopulations of GABAergic neurons in the mouse lateral septum(LS) expressing somatostatin(SST) and calbindin1(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 rhythm 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. The vCA1d?SST+-dLS?lateral hypothalamic area (LHA) circuit positively regulates social memory acquisition, whereas thevCA1v?CB+-vLS?anterior hypothalamic nucleus (AHN) pathway negatively regulates it. This study uncovers two parallel subcortical neural circuits underpinning the dynamic regulation of social memory. Overall design: The lateral septum tissue of male C57BL/6 mice at 2-month old were taken for single cell RNA-seq