A hypothalamic node for the cyclical control of female sexual rejection

Internal state-dependent behavioral responses, such as the switch between rejection and acceptance of sexual advances depending on a females reproductive capacity, are fundamental to maintain social interactions and wellbeing. Here we characterize a dedicated circuit for the cyclical control of rejection behavior in the mouse, located in the anterior ventrolateral ventromedial hypothalamus (aVMHvl). In vivo recordings reveal that progesterone receptor expressing neurons of the aVMHvl (aVMHvlPr+) are active during rejection but silent when females accept the male. Moreover, we show that aVMHvlPr+ neurons receive reduced excitatory to inhibitory synaptic input balance during the receptive phase of the reproductive cycle. Finally, optogenetic activation of aVMHvlPr+ neurons in receptive females is sufficient to increase rejection behavior, disrupting the probability of copulation, without affecting other male-directed interactions. This population of aVMHvlPr+ neurons is thus a key neural substrate controlling female sexual behavior, providing an additional barrier to mating when fertilization is not possible.