Biased Oxytocinergic Modulation of Midbrain Dopamine Systems

Lei Xiao, Michael F. Priest, Jordan Nasenbeny, Ting Lu, Yevgenia Kozorovitskiy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


The release of dopamine (DA) regulates rewarding behavior and motor actions through striatum-targeting efferents from ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Here, we map and functionally characterize axonal projections from oxytocin neurons in the hypothalamic paraventricular nucleus to midbrain DA regions. Electrophysiological recordings of DA neurons reveal that both the application of oxytocin and optogenetic stimulation of oxytocinergic terminals suffice to increase DA neuron activity in the VTA but downregulate it in SNc. This biased modulation is mediated by oxytocin and vasopressin G-protein-coupled receptors. Oxytocin release directly activates DA neurons and indirectly inhibits them through local GABA neurons, but the relative magnitudes of the two mechanisms differ in VTA and SNc. Oxytocin-modulated DA neurons give rise to canonical striatal projections. Since hypothalamic oxytocinergic projections also target the striatum, oxytocin is poised to bias the balance of DA tone through multiple sites in vertebrate reward circuits. Xiao et al. reveal oxytocinergic projections from PVN to VTA and SNc, where, by different circuit and receptor mechanisms, oxytocin release biases dopamine neuron activity in opposite directions. This work places dopamine signaling under prominent control of a peptide neuromodulator.

Original languageEnglish (US)
Pages (from-to)368-384.e5
Issue number2
StatePublished - Jul 19 2017


  • PVN
  • SNc
  • VTA
  • dopamine
  • oxytocin
  • parvocellular

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Biased Oxytocinergic Modulation of Midbrain Dopamine Systems'. Together they form a unique fingerprint.

Cite this