A sensory neuron driver circuit in the colon
Abstract/Contents
- Abstract
- Within the gastrointestinal (GI) tract resides an entire nervous system devoted to coordinating its function autonomously, and which does not require any instruction from the brain. The enteric nervous system is composed of motor neurons, interneurons, and crucially its own intrinsic sensory neurons. These sensory neurons respond to local stimuli and coordinate movement of contents along the GI tract by instructing motility circuitry to relax and contract the gut. Additionally, in the colon, widespread synchro-nous oscillatory 1-2Hz activation of the ENS occurs at a set pace, every few minutes, resulting in rhythmic contractions all along its length. This motility pattern is called the colonic motor complex (CMC). Though sensory neurons were initially proposed as drivers of CMCs, that theory has long been discounted for a lack of further evidence of sensory neuron interconnectivity, synaptic input, or participation in CMCs. Here, I iden-tify cadherin-6 (Cdh6) as a novel marker of colonic sensory neurons, confirmed by im-munohistochemical, morphological, and electrophysiological methods, including the first recording of IH, a rhythmicity-associated current, in mouse colonic sensory neurons. A homophilic synaptic cell adhesion protein, Cdh6 expression only in sensory neurons suggests the presence of an interconnected sensory neuron network. I then show that optogenetic activation of Cdh6+ sensory neurons is sufficient to evoke CMCs. Finally, I demonstrate that pharmacologic blockade of IH in sensory neurons abolishes spontane-ous CMCs. These results revive a largely abandoned decades old theory of a sensory neuron driver circuit in the colon, and place sensory neurons firmly back in control of the entire ENS, not just local microcircuits.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2024; ©2024 |
| Publication date | 2024; 2024 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gomez-Frittelli, Julieta |
|---|---|
| Degree supervisor | Kaltschmidt, Julia |
| Degree supervisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Kaltschmidt, Julia |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Becker, Laren |
| Thesis advisor | Kauer, Julie |
| Degree committee member | Becker, Laren |
| Degree committee member | Kauer, Julie |
| Associated with | Stanford University, School of Engineering |
| Associated with | Stanford University, Department of Chemical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Julieta Gomez-Frittelli. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2024. |
| Location | https://purl.stanford.edu/dg552cj1654 |
Access conditions
- Copyright
- © 2024 by Julieta Gomez-Frittelli
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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