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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2016

Month Degree Awarded

September

First Advisor

Luke Remage-Healey

Second Advisor

R. Thomas Zoeller

Third Advisor

Geng-Lin Li

Fourth Advisor

Lisa M. Minter

Subject Categories

Behavioral Neurobiology | Cell Biology | Molecular and Cellular Neuroscience

Abstract

Estradiol, traditionally known as a hormone that communicates with distant cells in the body, is also synthesized locally in the brain to act as a neuromodulator. Neuromodulators differ from neurotransmitters in that they simultaneously affect a population of neurons and their actions are not limited to the synapse. One of the many effects of estradiol signaling is rapid modulation of auditory processing in response to external stimuli. The enzyme required for estradiol synthesis, aromatase, is highly expressed in the regions that are involved in higher-order processing of sounds in humans and songbirds. Since zebra finches, a type of songbird, are one of the few laboratory animals that communicate via complex learned vocalization, they are commonly used as a model for vocal learning and auditory processing. Although many aspects of the actions of estradiol in the zebra finch forebrain have been revealed, little is known regarding how estradiol levels are regulated via aromatase activity. First, this dissertation describes the procedure for in vivo microdialysis, a method that allows local estradiol detection in freely moving animals. Second, using in vivo microdialysis, we investigated whether another neuromodulator, norepinephrine, regulates global estradiol levels within a secondary auditory region, caudomedial nidopallium (NCM). The results showed no evidence that norepinephrine has a major role in controlling estradiol levels in the NCM. However, in vivo electrophysiological vi recordings from the NCM revealed that norepinephrine has a similar role in auditory processing as estradiol but acts via a different mechanism. Finally, the dissertation examined the identities and organization of aromatase-expressing neurons and found that the heterogeneity of aromatase cells was different between different aromatase-positive regions. Aromatase-expressing cell bodies were found to be more prominent in regions with low expression of a transmembrane G-protein coupled estrogen receptor, GPER1, while high pre-synaptic aromatase-expressing regions expressed high amounts of GPER1. Moreover, aromatase-expressing cells were found in somato-somatic clusters. Preliminary data injecting dyes in clustered cells indicate that the neurons in clusters may be communicating with one another through gap junctions. Overall, this dissertation provides new knowledge for understanding the relationship between neuronal interactions and aromatase signaling in the context of auditory processing.

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