PVN-NAc Shell-VP Circuit OT and OTR Neurons Regulate Pair Bonding via D2R and D1R

J Neurosci. 2025 Jun 11;45(24):e2061242025. doi: 10.1523/JNEUROSCI.2061-24.2025.

Abstract

Previous studies have found that several neurochemicals are involved in formation of pair bonding. However, the circuit mechanisms underlying pair bonding, especially how these chemicals interact in this circuit to regulate pair bonding, remain unclear. Using male mandarin voles, the present study shows that cohabitation with a partner increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) of paraventricular nucleus (PVN) oxytocin (OT) neurons projecting to the nucleus accumbens (NAc) shell. Optogenetic activation of PVN OT neurons projecting to the NAc shell reduced the activity of D2 medium spiny neurons (MSNs) but increased the activity 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 noncohabitated male voles. This OT-induced LTD in the NAc shell D1/D2 MSNs was suppressed by 7 d 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 MSN 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.

Keywords: OT system; PVN–NAc shell–VP circuit; dopamine receptor; pair bonding.

MeSH terms

  • Animals
  • Arvicolinae
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Male
  • Neural Pathways / physiology
  • Neurons* / drug effects
  • Neurons* / physiology
  • Nucleus Accumbens* / cytology
  • Nucleus Accumbens* / physiology
  • Optogenetics
  • Oxytocin* / metabolism
  • Oxytocin* / pharmacology
  • Oxytocin* / physiology
  • Pair Bond*
  • Paraventricular Hypothalamic Nucleus* / cytology
  • Paraventricular Hypothalamic Nucleus* / physiology
  • Receptors, Dopamine D1* / metabolism
  • Receptors, Dopamine D1* / physiology
  • Receptors, Dopamine D2* / metabolism
  • Receptors, Dopamine D2* / physiology
  • Receptors, Oxytocin* / metabolism
  • Receptors, Oxytocin* / physiology

Substances

  • Receptors, Dopamine D2
  • Oxytocin
  • Receptors, Dopamine D1
  • Receptors, Oxytocin