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.

Dendritic arbor of neurons in the hypothalamic ventromedial nucleus in female prairie voles (Microtus ochrogaster).

Female mating behavior in rats is associated with hormone-induced changes in the dendritic arbor of neurons in the ventromedial nucleus of the hypothalamus (VMH), particularly the ventrolateral portion. Regulation of mating behavior in female prairie voles differs substantially from that in rats; therefore, we examined the dendritic morphology of VMH neurons in this species. Sexually naïve adult female prairie voles were housed with a male to activate the females' reproductive endocrine system. Following 48 h of cohabitation, females were tested for evidence of reproductive activation by assessing the level of male sexual interest, after which their brains were processed using Golgi impregnation, which allowed ventrolateral VMH neurons to be visualized and analyzed. Dendritic arborization in the female prairie vole VMH neurons was strikingly similar to that of female rats. The key difference was that in the prairie voles the long primary dendrites extended considerably further than those observed in rats. Although most female voles paired with males exhibited sexual activation, some females did not. These two groups displayed specific differences in their VMH dendrites. In particular, the long primary dendrites were longer in the reproductively active females compared with those in the non-activated females. Overall, dendrite lengths were positively correlated with plasma estradiol levels in females exposed to males, but not in unpaired females. Although causal relationships between the neuroendocrine events, dendrite length, and the outward, behavioral manifestation of reproductive activation cannot be determined from this study, these results suggest an association between ventrolateral VMH dendrite morphology and female mating behavior in prairie voles, akin to what has been observed in female rats.