Ovarian Hormone-Induced Neural Plasticity in the Hypothalamic Ventromedial Nucleus

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Doctor of Philosophy (PhD)
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dendritic spines
neural plasticity
sexual behavior
ventromedial hypothalamus
Neuroscience and Neurobiology
Social and Behavioral Sciences
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Ovarian hormones act throughout the brain and body to influence a range of functions and behaviors. Estrogens and progesterone are neuroprotective and have important health implications. However, our understanding of the mechanisms underlying many of their actions is incomplete. The goal of this thesis is to elucidate details of ovarian hormone-induced neural plasticity, specifically as it relates to female reproductive behavior and dendritic morphology in the hypothalamic ventromedial nucleus (VMH). First, I tested the hypothesis that the mechanisms of female receptivity are conserved across two species with very different mating strategies: prairie voles, which exhibit monogamy, induced estrous, and induced ovulation, and rats, which do not. Utilizing Golgi impregnation, I demonstrated that, as in rats, dendrite length in the VMH of female prairie voles is correlated with mating status, which in turn is associated with estradiol concentration. Next, I tested the hypothesis that oxytocin, a neuromodulator that promotes mating behavior, is a marker for estradiol-induced synaptic reorganization in the VMH. Using immunoelectron microscopy, I revealed that estradiol reduces the presence of dendrites that extend out into the adjacent lateral fiber plexus and increases the innervation of the remaining dendrites, which have internalized oxytocin. Finally, I tested the hypothesis that estradiol has short-term effects on proteins associated with synaptic reorganization, namely the actin-associated protein cofilin and ionotropic AMPA glutamate receptor subunits GluA1 and GluA2 in the VMH. Using immunohistochemistry, I discovered that estradiol rapidly alters phosphorylation of cofilin and the levels of GluA1. Together, these findings demonstrate that estradiol actions in the VMH are evolutionarily conserved, affect oxytocin synapses, and rapidly alter regulation of actin polymerization and glutamate signaling.

Loretta M. Flanagan-Cato
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