Jaime A. Willett
Changes in striatal function are linked to changes in neuroendocrine state. Indeed, dopamine dynamics, receptor expression, and performance in striatal-mediated sensorimotor and learning behaviors vary with cyclical fluctuations of estrogen in females. However, the underlying mechanisms remain poorly understood, particularly regarding synaptic plasticity. In the dorsal striatum, excitatory afferents from cortex, thalamus, and substantia nigra converge on medium spiny neurons (MSNs). MSNs act as the initial integrators, with changes in synaptic plasticity being one mechanism by which they modulate behavioral output. MSNs express membrane-associated estrogen receptors, which can activate metabotropic glutamate receptor signaling, and thus potentially modulate synaptic plasticity. In male dorsal striatal MSNs, endogenous estradiol interacts with the dopaminergic system to modulate long-term potentiation (LTP). In female rats, estrous cycle-dependent variation exists in multiple measures of MSN excitability including threshold and peak firing rate. Evidence from other estradiol-sensitive regions of the brain indicate that cyclical changes in estradiol in females is capable of modulating synaptic plasticity. Given the cyclical fluctuation of estradiol, dopamine, and MSN intrinsic excitability, I hypothesize that expression of dorsal striatal MSN synaptic plasticity, as measured by LTP, is elevated in adult females when estradiol is high relative to when estradiol is low. Using whole-cell patch clamp electrophysiology, I will test whether the amplitude of dorsal striatal MSN LTP differs by estrous cycle stage and elucidate the involvement of endogenous estradiol. This research represents the first time that striatal LTP will be assessed in the context of the estrous cycle and specifically reported in female animals.