Abstract
Social cognition enables individuals to understand others' intentions. Social memory is a necessary component of this process, for without it, subsequent encounters are devoid of any historical information. The CA2 area of the hippocampus, particularly the vasopressin 1b receptor (Avpr1b) expressed there, is necessary for memory formation. We used optogenetics to excite vasopressin terminals, originating from the hypothalamic paraventricular nucleus, in the CA2 of mice. This markedly enhanced their social memory if the stimulation occurred during memory acquisition, but not retrieval. This effect was blocked by an Avpr1b antagonist. Finally, this enhanced memory is resistant to the social distraction of an introduced second mouse, important for socially navigating populations of individuals. Our results indicate the CA2 can increase the salience of social signals. Targeted pharmacotherapy with Avpr1b agonists or deep brain stimulation of the CA2 are potential avenues of treatment for those with declining social memory as in various dementias.
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Acknowledgements
We thank Emily Shepard for assistance with mouse colony maintenance and genotyping. We are grateful for the gifts of the vasopressin antibody from Harold Gainer and HSV from Ted Usdin. Alex Avram kindly wrote the software we used to control the optogenetic stimulations. We also thank Stafford Lightman and Michael Brownstein for their comments on a previous version of this manuscript. This research was supported by the intramural research program of the NIMH (ZIA-MH-002498-24).
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Smith, A., Williams Avram, S., Cymerblit-Sabba, A. et al. Targeted activation of the hippocampal CA2 area strongly enhances social memory. Mol Psychiatry 21, 1137–1144 (2016). https://doi.org/10.1038/mp.2015.189
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DOI: https://doi.org/10.1038/mp.2015.189
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