Targeted activation of the hippocampal CA2 area strongly enhances social memory.

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.

Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only.

Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care.