Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Wenqin Luo

Second Advisor

Minghong Ma

Abstract

Somatosensation allows us to perceive sensory stimuli at the surface of the body, and includes the sensations associated with pain and itch. Under normal conditions, these sensations alert us to the presence of potential danger or irritants, but pathological manifestations of pain and itch can become chronic and highly debilitating for patients. However, many of the mechanisms underlying pain and itch remain unknown. In Chapter 1, I present an overview of the molecules mediating the initial detection of stimuli associated with pain and itch, discuss some of the current models for pain and itch circuits as information travels from the periphery to the spinal cord, and end with a review of the latest techniques involved in studying somatosensation. In Chapter 2, I investigate the role of TRPC3 in β-alanine induced itch (Dong et al., 2017). TRPC3 is a member of the TRP family of cation-permeable ion channels and is expressed in sensory neurons, but its function within the context of somatosensation is unknown. I show that TRPC3 is dispensable for β-alanine induced itch behavior, other acute somatosensory behaviors, and the response to β-alanine at the cellular level. In Chapter 3, I provide insights into methods of studying how Aβ mechanoreceptor neurons modulate pain. I document the mouse genetics techniques used to obtain transgenic mouse lines that allow for the expression of light-activated opsins specifically in Aβ mechanoreceptors, and show that RetCreERT2; RosaChR2 treated mice and SplitCre; AdvillinFlp; RosaReaChR mice mediate recombination in Aβ mechanoreceptors. I then describe the caveats and challenges associated with producing these transgenic mice, such as the presence of nonspecific recombination. In sum, the findings presented here bring new insights into the mechanisms underlying itch, while offering new strategies for the study of pain mechanisms.

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