Meerschaert, Kimberly A.
(2021)
The role of primary afferents from different levels of the neuraxis in colon function.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Visceral organs receive sensory innervation from primary afferents arising from multiple levels of the neuroaxis. The reason for these different levels of sensory innervation remains a mystery. The colon receives extrinsic primary afferent neuron (ExPAN) input from thoracolumbar (TL; T10-L2) and lumbosacral spinal levels (LS; L5-S1) and the nodose ganglion (NG). Hypotheses for this dual innervation include: a) that different levels of innervation are involved in different qualitative aspects of pain, b) that different levels are important for the integration of autonomic function, or c) that different levels play complementary roles in immune modulation. The first step in discerning the role of these different afferents is to characterize the molecular identity of afferents from different levels innervating the same organ. This was accomplished by creating a molecular profile of colon afferents from TL, LS, and NG using single cell RT-qPCR. Clustering of colon afferents based on gene expression revealed unique TL, LS, and NG clusters. Next, processes of extrinsic afferents course throughout the myenteric ganglia of the enteric nervous system, where data suggest that they have local effector functions through release of glutamate and/or neuropeptides (e.g. CGRP, substance P) or act indirectly through autonomic reflexes. However, there is little known on how different ExPANs modulate myenteric activity, nor how this may change in inflammatory states. Calcium imaging and optogenetic studies revealed the LS level is largely unaffected by colitis, however, the TL and NG afferents had increased activation after colonic inflammation. Finally, colitis induced changes in colon motility evoked by autonomic efferent fibers from different levels of the neuraxis was examined. Although TL sympathetic neurons were altered by colitis, the LS parasympathetics were unchanged. Results from these studies indicate that different levels of the neuraxis have unique and overlapping functions during naïve states, and colonic inflammation alters specific levels of the neuraxis.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Albers, Kathryn M. | | | | | Committee Member | Gold, Michael S. | | | | | Committee Member | Koerber, H. Richard | | | | | Committee Member | Levinthal, David J. | | | | | Committee Member | Ross, Sarah E. | | | | | Committee Member | Christianson, Julie A. | | | | | Thesis Advisor | Davis, Brian M. | | | |
|
| Date: |
25 August 2021 |
| Date Type: |
Publication |
| Defense Date: |
14 May 2021 |
| Approval Date: |
25 August 2021 |
| Submission Date: |
10 August 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
155 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
colon, primary afferent, vagus, spinal |
| Date Deposited: |
26 Aug 2021 02:35 |
| Last Modified: |
26 Aug 2021 02:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41636 |
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