Estradiol regulates markers of synaptic plasticity in the hypothalamic ventromedial nucleus and amygdala of female rats.

Ovarian hormones act in multiple brain regions to modulate specific behaviors and emotional states. For example, ovarian hormones promote female sexual receptivity in the hypothalamic ventromedial nucleus (VMH) and modulate anxiety in the amygdala. Hormone-induced changes within the VMH include structural modifications, such as changes in dendritic spines, dendrite length and the number of synapses. In some situations, dendrite remodeling requires actin polymerization, which depends on phospho-deactivation of the enzyme cofilin, or the ionotropic AMPA-type glutamate receptors, especially the GluA1 and GluA2 subunits. The present experiments used immunohistochemistry to test the hypothesis that ovarian hormone-induced neural plasticity in the VMH and amygdala involves the regulation of phospho-cofilin, GluA1 and GluA2. These proteins were assessed acutely after estradiol administration (0.5, 1.0 and 4.0h), as well as three days after hormone treatment. Both brain regions displayed rapid (4.0h or less) and transient estradiol-induced increases in the level of phospho-cofilin. At the behaviorally relevant time point of three days, differential changes in AMPA receptor subunits were observed. Using Golgi impregnation, the effect of estradiol on amygdala dendrites was examined. Three days after estradiol treatment, an increase in the length of dendrites in the central nucleus of the amygdala was observed. Thus, estradiol initiates structural changes in dendrites in both the VMH and amygdala associated with an early phospho-deactivation of cofilin, followed by dynamic, brain region-specific changes in AMPA receptor composition.