Synaptic cell adhesion molecule Cdh6 identifies a class of sensory neurons with novel functions in colonic motility
Year: 2025
Type: article
Abstract: Intrinsic sensory neurons are an essential part of the enteric nervous system (ENS) and play a crucial role in gastrointestinal tract motility and digestion. Neuronal subtypes in the ENS have been distinguished by their electrophysiological properties, morphology, and expression of characteristic markers, notably neurotransmitters and neuropeptides. Here we investigated synaptic cell adhesion molecules as novel cell type markers in the ENS. Our work identifies two Type II classic cadherins, Cdh6 and Cdh8, specific to sensory neurons in the mouse colon. We show that Cdh6+ neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression of Calcb and Nmu , Dogiel type II morphology and AH-type electrophysiology and I H current. Optogenetic activation of Cdh6+ sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated current I H disrupts the spontaneous generation of CMCs. These findings provide the first demonstration of selective activation of a single neurochemical and functional class of enteric neurons, and demonstrate a functional and critical role for sensory neurons in the generation of CMCs. One-Sentence Summary Intrinsic sensory neurons of the enteric nervous system in the mouse distal colon exclusively express synaptic cell adhesion molecules Cdh6 and Cdh8, evoke retrograde colonic motor complexes (CMCs) when stimulated, and possess rhythmicity-associated I H current, involved in producing spontaneous CMCs.
Source: eLife
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Institutes of Health, School of Medicine, Stanford University, Wu Tsai Neurosciences Institute, Stanford University, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G3282988249, Wireless optogenetic induction of gastrointestinal transit in conscious mice, Tracking pre-seizure dynamics to predict and control seizures, How Spinal Afferent Neurons Control Appetite and Thirst , Stanford Chem-H Chemistry/Biology Interface Predoctoral Training Program, Inhibitory Controls of Thalamic Neurons, Development and Patterning of the Enteric Nervous System, G9000231523, Stanford Alzheimer's Disease Research Center
OpenAlex ID: W4401416387