TY - JOUR
T1 - A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion
AU - Scott, Niv
AU - Prigge, Matthias
AU - Yizhar, Ofer
AU - Kimchi, Tali
N1 - We thank M. Dayan, E. Elharrar, I. Sofer, Y. Pen, Y. Beny, N. Zhilka and E. Massasa for their assistance with the experiments; R. Levy for help with virus production; A. Chen and A. Ramot for sharing equipment and reagents. A. Mizrahi, S. Wagner, and the Yizhar and Kimchi groups, for comments on the manuscript; D. Anderson for providing the Cre-dependent anterograde virus and V. Grinevich for providing the OT:Venus virus. M.P. was supported by the Clore Center for Biological Physics and a Minerva postdoctoral fellowship. This work was supported by grants from Minerva Foundation 711131, Women’s Health Research Center, Gruber Foundation 720667, ISF 1324/15, the Jenna and Julia Birnbach Career Development Chair to T.K.; and Marie Curie CIG 321919, ERC StG 337637, ISF 1351/12, the Nollman Career Development Chair to O.Y. Contributions - N.S. performed all behavioural, neuronal tracing and in vivo physiological experiments. M.P. cloned the TH-overexpression viral vector and performed the in vitro electrophysiology experiments. O.Y. supervised the electrophysiology experiments and assisted in designing the optogenetic assays. T.K. planned and supervised all the experiments. T.K. and N.S. interpreted the results and wrote the paper together with M.P. and O.Y.
PY - 2015/9/24
Y1 - 2015/9/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84942543809&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/nature15378
DO - https://doi.org/10.1038/nature15378
M3 - مقالة
SN - 0028-0836
VL - 525
SP - 519
EP - 522
JO - Nature
JF - Nature
IS - 7570
ER -