Date of Award

Summer 8-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The vestibular system sense gravity and self-motion to help animals maintain body balance. Although vestibular signals inform the brain of the directions and speed of our body movements, it still remains unclear how these sensory information are processed and organized in the central nervous system. My thesis aims to illustrate neural computation underlying central vestibular tuning and the topographic organization of the vestibular circuits. First I established a novel approach to perform whole-cell recording of synaptic inputs in vivo during multi-axis movements in the central vestibular neurons. This technical advance allowed me to simultaneously measure presynaptic and postsynaptic tuning, along with the presynaptic convergence pattern and synaptic strengths, all at the larval zebrafish vestibulospinal nucleus. I showed that convergence of inputs with dissimilar sensory responses can create complex postsynaptic tuning, whereas convergence of inputs with similar responses mediates simpler postsynaptic tuning. This direct demonstration of how simple and complex vestibular tuning are computed centrally, resolved a major gap in the vestibular field between theoretical prediction and experimental evidence. Next, I used serial-section electron microscopy to reconstruct a high- resolution ultrastructure of the entire vestibular peripheral circuit. I mapped the connectivity of all 91 vestibular hair cells and 105 afferents in one utricle and traced afferent projections to the vestibular brainstem. This work reveals the first known topographic map organized by both sensory tuning and developmental age in the vestibular ganglion. It also shows that the early born and late born peripheral pathways coincide with two vestibular streams encoding the phasic and tonic signals, respectively. Together my study suggests that vestibular circuits from the peripheral sensors to the central neurons are potentially organized by development and movement speed.

Language

English (en)

Chair and Committee

Martha W. Bagnall Timothy Holy

Committee Members

Daniel Kerschensteiner, Lawrence H. Synder, Bruce A. Carlson,

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