PVN-NAc shell-VP circuit OT and OTR neurons regulate pair bonding via D2R and D1R

Previous studies have found that several neurochemicals are involved in formation of pair bonding. However, circuit mechanisms underlying pair bonding, especially how these chemicals interact in this circuit regulate pair bonding, remains unclear. Using male mandarin voles, the present study shows that cohabitation with a partner increased frequency of spontaneous excitatory postsynaptic current (sEPSC) of paraventricular nucleus (PVN) oxytocin (OT) neurons projecting to nucleus accumbens (NAc) shell. Optogenetic activation of PVN OT neurons projecting to the NAc shell reduced D2 medium spiny neurons (MSNs) activity, but increased activities of D1 MSNs in the NAc shell. Bath application of OT caused a long-term depression (LTD) of evoked excitatory postsynaptic current (eEPSC) in NAc shell D1/D2 MSNs in the no cohabitated male voles. This OT-induced LTD in the NAc shell D1/D2 MSNs was suppressed by 7 days of cohabitation. NAc shell oxytocin receptor (OTR) MSNs projecting to the ventral pallidum (VP) were D1R/D2R positive. Chemogenetic activation or inhibition of OTR MSNs in the NAc shell projecting to the VP facilitated or disrupted the pair bond formation respectively. The facilitatory effects of OTR MSNs activation on pair bond formation could be blocked by D2 antagonist, but not D1 antagonist. These results suggest that OT and OTR neurons in the PVN-NAc shell-VP circuit regulate pair bonding via different activities of D1/D2 MSNs. Significance Statement Pair bond is important for successful reproduction in monogamous species, while the mechanisms by which the neurochemicals interact to regulate formation of pair bonding remain unclear. Using whole cell patch-clamp recordings, we confirmed that cohabitation with opposite sexes alters the synaptic transmission of OT neurons in the PVN and the effects of OT on D1 and D2 MSNs in the NAc. We then unveiled that optogenetic activation of PVN OT neurons influence activities of D1 and D2 MSNs in the NAc shell and manipulation of VP-projecting OTR MSNs in the NAc shell affected pair bonding formation. Our findings identify that OT and dopamine system interact in the PVN-NAc shell-VP neural circuits modulate formation of pair bonding.