VMHvllCckar cells dynamically control female sexual behaviors over the reproductive cycle

Abstract

Sexual behavior is fundamental for the survival of mammalian species and thus supported by dedicated neural substrates. The ventrolateral part of ventromedial hypothalamus (VMHvl) is an essential locus for controlling female sexual behaviors, but recent studies revealed the molecular complexity and functional heterogeneity of VMHvl cells. Here, we identify the cholecystokinin A receptor (Cckar)-expressing cells in the lateral VMHvl (VMHvll^Cckar) as the key controllers of female sexual behaviors. The inactivation of VMHvll^Cckar cells in female mice diminishes their interest in males and sexual receptivity, whereas activating these cells has the opposite effects. Female sexual behaviors vary drastically over the reproductive cycle. In vivo recordings reveal reproductive-state-dependent changes in VMHvll^Cckar cell spontaneous activity and responsivity, with the highest activity occurring during estrus. These in vivo response changes coincide with robust alternation in VMHvll^Cckar cell excitability and synaptic inputs. Altogether, VMHvll^Cckar cells represent a key neural population dynamically controlling female sexual behaviors over the reproductive cycle.

Keywords: cholecystokinin A receptor; female sexual behavior; maternal aggression; neural plasticity; reproductive cycle; ventrolateral part of ventromedial hypothalamus.