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Author ORCID Identifier
Campus-Only Access for One (1) Year
Doctor of Philosophy (PhD)
Year Degree Awarded
Month Degree Awarded
Behavioral Neurobiology | Molecular and Cellular Neuroscience
Locomotion is critical for the survival of vertebrate animals and features well conserved mechanisms and patterns of muscular action and neural firing. It relies upon a balance of excitatory and inhibitory neurotransmitter systems within neural networks of the central nervous system. GABA is a classically inhibitory neurotransmitter recognized as a key regulator of these neural networks. GABAA receptors (GABAARs) mediate the rapid responses to GABA. Despite its importance, the precise roles and molecular mechanisms of GABA remain unclear due to the complexities of GABA signaling. Conservation of receptor structure and function allow researchers to use the advantages of simpler systems such as developing zebrafish (Danio rerio). Here, I hypothesize that locomotion is regulated through a few GABAA receptor subunits and therefore a few receptor subtypes in a number of spinal cord neurons early in development. Results using a somatic mutation screen approach suggest α3, α4 and α5 containing receptors play significant roles in locomotor regulation in comparison to the rest of their α subunit family members.
Obligatory GABAA receptor α subunits, are expressed in restricted patterns early in development including the spinal cord. I hypothesize GABAergic signaling imposes a regulatory effect on locomotion at the level of the spinal cord in cell types involved in the locomotor network. Results suggest α3, α4 and α5 are among the receptor subtypes that are responsible for this regulatory role within the spinal locomotor network. To test this, I perform lesion analyses to remove supraspinal input in newly established GABAA receptor α subunit mutants which better elucidate the role of spinal GABAergic signaling in locomotor command. Dual fluorescent in situ hybridization is then utilized to show that gabra3 is expressed in a broad array of spinal locomotor neurons. This work also shows spinal gabra4 expression is limited to a highly conserved population of GABAergic CSF contacting neurons (CSF-cNs).
Overall, the data here serves as a starting point to improve tracking the changes in signaling characteristics of these fundamental locomotion–associated neurons. Generally, the insights from this dissertation increase our understanding of the circuitry that dictates how vertebrates move through their environment.
Barnaby, Wayne, "Characterizing the Roles of GABA(A) Receptor ɑ Subunits in Locomotion in Developing Zebrafish" (2023). Doctoral Dissertations. 2798.
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