The Contribution of Hippocampal Oxytocin Receptors to Social Memory Processing

Abstract

Recent studies have highlighted growing evidence that the hippocampus assumes an underappreciated role in promoting social memories. However, the mechanisms by which discrimination of social and non-social stimuli are differentiated in the hippocampus are not known. The social hormone oxytocin has long been understood to promote discrimination of social stimuli. Remarkably, the physiological functions of oxytocin receptors (Oxtrs) in the mouse hippocampus are not known. Here, we demonstrate using genetic approaches that Oxtrs in the anterior dentate gyrus (aDG) of mice are necessary for discrimination of social, but not non-social, stimuli. In contrast, Oxtrs in pDG promote sociability without influencing social memory. We further demonstrate using genetic, pharmacological, and ensemble mapping strategies that Oxtrs in aCA2/CA3 recruit a population-based coding mechanism to mediate social stimuli discrimination. Optogenetic dissection of aCA2/CA3 outputs revealed a double dissociation by which social information in aCA2/CA3 is mediated to posterior CA1, while non-social information is mediated to aCA1. Collectively, these studies identify a role for an aDG-CA2/CA3 axis of Oxtr expressing cells in discrimination of social stimuli and delineate a pathway relaying social memory computations in the anterior hippocampus to the posterior hippocampus to guide social recognition.