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Arts & Sciences Electronic Theses and Dissertations

2021

Development

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Full-Text Articles in Life Sciences

Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn Aug 2021

Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn

Arts & Sciences Electronic Theses and Dissertations

Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective …


Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu Aug 2021

Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu

Arts & Sciences Electronic Theses and Dissertations

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 …


The Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler Aug 2021

The Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler

Arts & Sciences Electronic Theses and Dissertations

Mosaicism is pervasive in humans and yet we understand little of its causes and functional consequences across the lifespan. To help solve these mysteries, we developed a suite of tools, called Lachesis, to analyze postzygotic mutations (PZMs). LachesisDetect is a novel and accurate method to detect PZMs with VAFs as low as 0.04% from bulk RNA-seq samples. LachesisMap is an innovative supervised method to reconstruct postzygotic mutation phylogenies from putative prenatal PZMs. We applied Lachesis to 17,382 samples derived from 948 donors across 54 diverse tissues and cell types from the NIH’s Genotype-Tissue Expression (GTEx) project to produce the most …