A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion

Nature. 2015 Sep 24;525(7570):519-22. doi: 10.1038/nature15378. Epub 2015 Sep 16.


It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex-specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression
  • Animals
  • Anterior Hypothalamic Nucleus / cytology
  • Anterior Hypothalamic Nucleus / enzymology
  • Anterior Hypothalamic Nucleus / physiology
  • Dopaminergic Neurons / enzymology
  • Dopaminergic Neurons / metabolism
  • Female
  • Hypothalamus / cytology*
  • Hypothalamus / enzymology
  • Hypothalamus / physiology*
  • Male
  • Maternal Behavior / physiology*
  • Mice
  • Oxytocin / blood
  • Oxytocin / metabolism*
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / enzymology
  • Paraventricular Hypothalamic Nucleus / physiology
  • Postpartum Period
  • Sex Characteristics*
  • Synapses / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Oxytocin
  • Tyrosine 3-Monooxygenase