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

Xiaoting Wu, Wade Morishita, Kevin T. Beier, Boris D. Heifets and Robert C. Malenka ()
Additional contact information
Xiaoting Wu: Stanford University
Wade Morishita: Stanford University
Kevin T. Beier: University of California, Irvine
Boris D. Heifets: Stanford University
Robert C. Malenka: Stanford University

Nature, 2021, vol. 599, issue 7883, 96-101

Abstract: Abstract Social memory—the ability to recognize and remember familiar conspecifics—is critical for the survival of an animal in its social group1,2. The dorsal CA2 (dCA2)3–5 and ventral CA1 (vCA1)6 subregions of the hippocampus, and their projection targets6,7, 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-HT1B 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 behaviours8,9, but also social memory, by influencing distinct target structures.

Date: 2021
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DOI: 10.1038/s41586-021-03956-8

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