Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Wenqin Luo

Second Advisor

Minghong Ma

Abstract

Tactile information is critical for our ability to manipulate objects, recognize textures, and provide motor feedback during locomotion. These sensations are conveyed by cutaneous low-threshold mechanoreceptors (LTMRs), which convey innocuous tactile sensations to local spinal circuits and to regions of the brain through direct connections. However, under pathological conditions, these neurons can aberrantly activate noxious pain sensations instead. Here, I explore developmental mechanisms of LTMRs and their mature functions under pathological conditions. In Chapter 2, we examine the role of a specialized population of roof plate-derived radial glial-like cells (RGLCs), which we show is necessary for the long-distance projections of rapidly adapting (RA) LTMRs to the brain. Using RNA sequencing, we show that these RGLCs express a variety of growth-promoting molecules that may support the axon growth of RA-LTMRs. With a sparse labeling technique, we show that in the absence of the RGLCs, the axons of RA-LTMRs fail to extend fully to the brain. Interestingly, this effect does not extend to other neuronal axon types within the same region of the spinal cord that typically do not innervate the brain directly. We conclude that RGLCs play a role in specifically supporting the growth of long-projecting RA- LTMRs. In Chapter 3, we explore the role LTMRs in pathological pain conditions. We describe the development of a transgenic mouse line, Aβ-ReaChR, in order to specifically activate the Aβ class of LTMRs using optogenetic stimulation using three different mouse lines, Split-Cre, Advillin-FlpO, and Rosa-ReaChR. We then discuss how these tools may be applied to test and define a role for Aβ-LTMRs in pathological pain conditions. Together, this work provides insight into the development mechanisms of touch neurons, and also provide a new strategy with which to probe their mature function.

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