A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion

Abstract

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.

Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish,Astatotilapia burtoni

“…Previous studies demonstrated sexually dimorphic regulation of dopaminergic signaling in the hypothalamus and pituitary of both mammals and fish (Goebrecht et al, 2014;Saha et al, 2015;Scott et al, 2015). Although androgenic steroids regulate dopamine receptor expression in the fish POA (Pasqualini et al, 2009), there are, to our knowledge, no studies testing for sex-specific differences in dopamine receptor-mediated inhibition of POA neural activity.…”

“…These results show that the inhibitory mechanisms postsynaptic to dopamine release onto POA GnRH1 neurons are not sexually dimorphic. However, presynaptic dopamine production or release could vary by sex; sexually dimorphic TH expression, as has been observed in fish and mammals (Saha et al, 2015;Scott et al, 2015), could result in sexually dimorphic regulation of dopaminergic control of reproductive behaviors (Goebrecht et al, 2014).…”

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

“…This might be mediated by prolactin itself but also by the closely related placental lactogens that act on the Prlr and are elevated in the blood throughout the second half of pregnancy (25). Importantly, unlike some recent reports that have used cell ablation approaches (26,27) or blockade of neurotransmitter production (28,29) to identify critical cell types mediating maternal behavior, in this model, the neuronal circuitry is completely intact. The profound deficit arises specifically from the lack of appropriate hormonal input into these circuits.…”

The genetic basis of parental care evolution in monogamous mice

“…Studies of monogamous and promiscuous voles defined a prominent role for the vasopressin and oxytocin pathways in affiliative behaviours, showing, for example, that differences in the spatial distribution of the vasopressin 1a receptor in the male brain are associated with changes in pair-bonding behaviour 2,3 . Oxytocin and vasopressin are known to regulate many aspects of parental care 4–7 , but how genetic variation in these pathways contributes to natural differences in parental care is poorly understood.…”