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Document Type

Campus-Only Access for One (1) Year

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Neuroscience and Behavior

Year Degree Awarded

2017

Month Degree Awarded

September

First Advisor

Luke Remage-Healey

Subject Categories

Molecular and Cellular Neuroscience

Abstract

Although several sex differences have been described in brain structure, function, and development, sex as a biological factor is underrepresented in neuroscience studies. In the mammalian brain, there are sex differences in the mechanism of rapid estradiol actions on neuronal physiology. In the songbird, the brain is a major source of estradiol production, and estradiol rapidly modulates auditory responsiveness through dynamic changes and an unknown receptor mechanism. I set out to determine if there are sex differences in rapid estradiol modulation of auditory cortical activity, as has been shown in other systems. I tested this hypothesis through three aims: 1) to determine whether the identity of interneurons in the auditory regions of the brain differs between the sexes,2) test whether acute, endogenous estradiol production is necessary for auditory responsiveness in both sexes and 3) test whether the membrane estrogen receptor GPER1 is necessary and sufficient to shape auditory-evoked activity in both sexes. I found that male and female estrogen-producing and estrogen-sensitive cells did not differ in coexpression with interneuron subtype markers in auditory cortical regions. I also determined that more regions of the male auditory cortex depend on acute, endogenous estrogen production for auditory-induced gene expression than that of females, indicating that males are more sensitive to acute-synthesis of estrogens than females. Finally, I found that narrow-spiking (NS) neurons in the caudomedial nidopallium are more associated with auditory responses than broad-spiking (BS) neurons in males whereas in females these cell types are similar. GPER1 is necessary for the full auditory responsiveness and coding but only in NS neurons of males, indicating an alternative receptor mechanism in females. In this dissertation, I describe a mechanism by which rapid estrogen modulates auditory responsiveness in males, but females have differences in the reliance on brain derived estradiol as well as receptors that mediate estradiol’s actions. This dissertation provides a framework to study sex differences using a mechanistic approach, and highlights the importance of sex as a biological variable in physiological studies even in brain regions with anatomical similarities.

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