Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Wenqin Luo

Abstract

Somatosensation allows us to perceive sensory stimuli at the surface of and inside the body. One sensation, itch, plays a protective role under acute conditions to alert us to potentially harmful stimuli, such as mosquitos, parasites, or irritating chemicals. Although helpful in these situations, the itch pathway can become chronically activated, leading to debilitating itch in patients suffering from chronic pruritus. Despite the many years of research on the molecular mediators and transmission of itch sensation, there is still much to learn about the complicated underpinnings of pruritus, particularly in the setting of dermatological illnesses. In Chapter 1, I present an overview of the molecular and cellular mediators of itch sensation, highlighting the role of immune cells in itch. After describing the initial activation of itch transmission, I discuss models of itch circuits. I end the chapter with a review of methods used to study itch sensation, focusing on mouse models of dermatological diseases used to study pruritus. In Chapter 2, I investigate the role of TrpC3 in antagonizing itch induced by a mouse model of contact dermatitis. Transient Receptor Potential Cation Channel Subfamily C Member 3 (TRPC3) is a cation-permeable ion channel that is expressed in cellular subtypes in a wide variety of systems (e.g., nervous system, immune system, cardiac system). TrpC3’s high level of expression in primary sensory neurons made it a prime candidate to function in modulating somatosensation, however previous studies identified little deficits in acute somatosensation in TrpC3 null mice. I show TrpC3 null mice display significantly increased pruritus with contact dermatitis (CD), pinpoint the importance of TrpC3 expression in DRG to antagonize itch sensation, and identify a decrease in nonpeptidergic subtype 1 (NP1+) MRGPRD+ neurons in TrpC3 null mice with CD. In sum, our findings identified a novel role of TrpC3 and NP1 afferents in CD pathology, which resulted in the proposal of a new model of modulation of itch sensation.

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Available to all on Friday, August 09, 2024

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