Estrogen selectively regulates spine density within the dendritic arbor ofrat ventromedial hypothalamic neurons

Estrogen acts in the hypothalamic ventromedial nucleus (VMH) to promote fem ale sexual behavior. One potential mechanism through which estrogen may fac ilitate this behavior is by reconfiguring synaptic connections within the V MH. Estrogen treatment increases the number of synapses and dendritic spine s in the VMH, but how this remodeling occurs within the context of the loca l, behaviorally relevant microcircuitry is unknown. The goal of this study was to localize estrogen-induced changes in spine density within the VMH an d relate these to dendritic morphology and the presence of nuclear estrogen receptor. The hypothalami from ovariectomized rats, treated with either ve hicle or estradiol, were lightly fixed, and VMH neurons were iontophoretica lly filled with Lucifer yellow. Confocal microscopy was used to examine neu ronal morphology. Estrogen treatment increased dendritic spine density by 4 8% in the ventrolateral VMH but had no effect on spine density in the dorsa l VMH. The primary dendrites of VMH neurons were differentially affected by estrogen. Estrogen treatment increased spine density twofold on the short primary dendrites but did not affect spine density on long primary dendrite s. Immunocytochemical staining showed that none of the filled neurons expre ssed estrogen receptor-alpha. Thus, although the effect of estrogen on spin e density is localized to a VMH subdivision where estrogen receptor is expr essed, estrogen treatment induces spines on neurons that lack estrogen rece ptor. Taken together, our results suggest that the effect of estrogen on ve ntrolateral VMH spines is selective within the dendritic arbor of a neuron and may be mediated by an indirect, possibly transynaptic, mechanism.