5-HT modulation of a medial septal circuit tunes social memory stability

Social memory—the ability to recognize and remember familiar conspecifics—is critical for the survival of an animal in its social group 1 , 2 . The dorsal CA2 (dCA2) 3 – 5 and ventral CA1 (vCA1) 6 subregions of the hippocampus, and their projection targets 6 , 7 , have important roles in social memory. However, the relevant extrahippocampal input regions remain poorly defined. Here we identify the medial septum (MS) as a dCA2 input region that is critical for social memory and reveal that modulation of the MS by serotonin (5-HT) bidirectionally controls social memory formation, thereby affecting memory stability. Novel social interactions increase activity in dCA2-projecting MS neurons and induce plasticity at glutamatergic synapses from MS neurons onto dCA2 pyramidal neurons. The activity of dCA2-projecting MS cells is enhanced by the neuromodulator 5-HT acting on 5-HT 1B receptors. Moreover, optogenetic manipulation of median raphe 5-HT terminals in the MS bidirectionally regulates social memory stability. This work expands our understanding of the neural mechanisms by which social interactions lead to social memory and provides evidence that 5-HT has a critical role in promoting not only prosocial behaviours 8 , 9 , but also social memory, by influencing distinct target structures.