Simultaneous Knockouts of the Oxytocin and Vasopressin 1b Receptors in Hippocampal CA2 Impair Social Memory

Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. The oxytocin (Oxtr) and vasopressin 1b (Avpr1b) receptors are co-expressed in the pyramidal neurons of the hippocampal subfield CA2 and are known to play a critical role in social memory formation. How the neuropeptides perform this function in this region is not fully understood. Here, we report the behavioral effects of a life-long conditional removal (knockout, KO) of either the Oxtr alone or both Avpr1b and Oxtr from the pyramidal neurons of CA2 as well as the resultant changes in synaptic transmission within the different fields of the hippocampus. Surprisingly, the removal of both receptors results in mice that are unable to habituate to a familiar female presented for short duration over short intervals but are able to recognize and discriminate females when presented for a longer duration over a longer interval. Importantly, these double KO mice were unable to discriminate between a male littermate and a novel male. Synaptic transmission between CA3 and CA2 is enhanced in these mice, suggesting a compensatory mechanism is activated to make up for the loss of the receptors. Overall, our results demonstrate that co-expression of the receptors in CA2 is necessary to allow intact social memory processing.