The synaptic organization of VMH neurons that mediate the effects of estrogen on sexual behavior

Estrogen acts in the hypothalamic ventromedial nucleus (VMH) of female rats to promote sexual behavior, as typified by the lordosis response. Morphological changes in the VMH, such as increased synaptic profiles and increased dendritic spines, suggest that estrogen may modulate behavior by altering VMH synaptic organization. To understand the significance of these changes, this laboratory has been investigating the functional classes of lordosis-relevant neurons and their local connectivity. A neurotropic virus, pseudorabies virus (PRV), was used to transneuronally label the CNS network that controls the lordosis-producing muscles. When PRV was placed in the lumbar epaxial muscles, it was sequentially detected in the lumbar ventral horn, the medullary reticular formation, the periaqueductal gray, and finally the VMH. Subsequent analysis showed that the population of VMH neurons that were initially infected with PRV largely resided beyond the cluster of estrogen receptor-containing neurons. In a separate study, VMH neurons were visualized with Lucifer yellow, and their morphology was analyzed using confocal microscopy. Such analysis confirmed that estrogen treatment increased dendritic spines in the VMH. The particular VMH neurons in this study did not express nuclear estrogen receptor, which suggests that estrogen can increase spine density indirectly. These results represent initial steps toward unraveling the local circuit that mediates estrogenic action on a specific reproductive behavior.