Estrogen -induced synaptic remodeling in the ventromedial nucleus of the hypothalamus and reproductive behavior in the female rat

The ovarian hormone estrogen affects mood, cognition, and behavior primarily through its actions in the brain. Estrogen also remodels synaptic connections in certain brain areas. Thus, estrogen may mediate its effects on behavior by altering synaptic connectivity in specific brain regions. Female rat sexual behavior, particularly the lordosis reflex, is an excellent model in which to study estrogen-induced synaptic remodeling and its effect on behavior. If estrogen alters synaptic connectivity to mediate behavior, then these estrogen-induced alterations should occur in brain regions and neuronal populations associated with female reproductive behavior. These experiments demonstrate that estrogen increases the density of dendritic spines, specialized sites of synaptic input, in a brain region critical for sexual behavior, namely, the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (vlVMH). This increase was not a generalized effect because estrogen did not alter spine density in the dorsomedial subdivision of the VMH. Immunocytochemical and morphological analysis revealed that the affected neurons did not possess estrogen receptor-α (ERα) nor project to the periaqueductal gray (PAG), a crucial segment in the lordosis efferent pathway. This suggests that estrogen induces spines in these neurons via a transynaptic mechanism. This project also revealed that estrogen affects spine density in a neuronal population associated with sexual behavior, namely vlVMH neurons that project to the PAG. However, in this case, estrogen decreased spine density. These results suggest that estrogen may have a differential effect on specific neuronal populations. As previous, the affected neurons did not contain ERα. Thus, in general, estrogen may mediate its effects on dendritic spines via a transynaptic mechanism. Finally, experiments were performed to determine whether the neuronal populations undergoing estrogen-induced synaptic remodeling were activated by reproductive behavior, as indicated by Fos immunohistochemistry. Mating induced Fos primarily in vlVMH neurons that did not contain ERα nor project to the PAG. This differential response to mating stimuli combined with changes in spine density specific to neuronal population suggest that the two neuronal populations undergoing synaptic remodeling may play different roles in the regulation of sexual behavior as part of a synaptically connected network in the VMH