%0 Journal Article %A Inês C. Dias %A Nicolas Gutierrez-Castellanos %A Liliana Ferreira %A Susana Q. Lima %T The structural and electrophysiological properties of progesterone receptor expressing neurons vary along the anterior-posterior axis of the ventromedial hypothalamus and undergo local changes across the reproductive cycle %D 2021 %R 10.1523/ENEURO.0049-21.2021 %J eneuro %P ENEURO.0049-21.2021 %X Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole recordings and intracellular labeling to characterize the electrophysiological and morphological properties of individual VMHvl neurons in naturally cycling females and report the existence of multiple electrophysiological phenotypes within the VMHvl. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR- neurons, depended systematically on the neuron’s location along the anterior-posterior axis of the VMHvl and the phase within the reproductive cycle. Prominent amongst this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomical and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.Significance StatementFluctuating levels of sex hormones coordinate female behavior with their reproductive capacity by acting on neurons expressing their specific receptors. However, it is poorly understood how this seemingly simple message is integrated in local circuits to coordinate complex behavioral responses. Here we show evidence that progesterone receptor expressing neurons of the VMHvl undergo local and specific changes in structure and physiology, suggesting a compartmentalized action of the fluctuating systemic levels of sex hormone across the reproductive cycle, depending on their location in this hypothalamic nucleus. %U https://www.eneuro.org/content/eneuro/early/2021/04/15/ENEURO.0049-21.2021.full.pdf