A sensory neuron driver circuit in the colon

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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.


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


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


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

© 2024 by Julieta Gomez-Frittelli
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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