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

Abstract

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.

The ventral CA2 region of the hippocampus and its differential contributions to social memory and social aggression

“…Although the results on CA1 and CA3 suggest a selective role for ventral hippocampus in social memory, a number of studies have now found that the CA2 region is critically important for the encoding, consolidation and recall of social memory 17–23 . In addition, CA2 directly regulates social aggression through a trisynaptic circuit to the lateral septum and hypothalamus.…”

“…Of particular note, CA2 is highly enriched in receptors for the social neuropeptides arginine vasopressin (AVP) 31 and oxytocin (OXT) 32 , where they contribute to regulating social behaviors. Thus, general deletion of the arginine vasopressin receptor 1b (Avpr1b) 33 or the oxytocin receptor 32 impairs social memory, as does the conditional deletion of both receptors when restricted to CA2 23 . In addition, general deletion of Avpr1b inhibits social aggression 33 and this phenotype can be rescued by selective viral expression of Avpr1b in dCA2 and nearby neurons 34 , indicating that AVP acting on Avpr1b expressed in dCA2 neurons is necessary to promote normal levels of aggression.…”