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

• Published in: Nature (London) Vol. 599; no. 7883; pp. 96 - 101
• Main Authors: Wu, Xiaoting, Morishita, Wade, Beier, Kevin T., Heifets, Boris D., Malenka, Robert C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-11-2021; Nature Publishing Group
• Subjects: 631/378/1595/1554; 631/378/3919; 9/74; Animals; Brain; CA2 Region, Hippocampal - cytology; CA2 Region, Hippocampal - physiology; Circuits; Conspecifics; Control stability; Female; Glutamatergic transmission; Glutamic Acid - metabolism; Humanities and Social Sciences; Male; Memory - physiology; Mice; Modulation; multidisciplinary; Neural Pathways; Neuromodulation; Neuronal Plasticity; Neurons; Optogenetics; Pyramidal cells; Pyramidal Cells - metabolism; Rabies; Receptor, Serotonin, 5-HT1B - metabolism; Science; Science (multidisciplinary); Septal Nuclei - cytology; Septal Nuclei - physiology; Septum; Serotonin; Serotonin - metabolism; Serotonin S1 receptors; Social Behavior; Social factors; Social interaction; Social interactions; Synapses; Synapses - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-03956-8

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.
Experiments in mice identify the medial septum as an extrahippocampal input region that is critical for social memory formation, and show that modulation of the medial septum by serotonin regulates the stability of social memories.