Synaptic cell adhesion moleculeCdh6identifies a class of sensory neurons with novel functions in colonic motility

Abstract

AbstractIntrinsic 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,Cdh6andCdh8,specific to sensory neurons in the mouse colon. We show thatCdh6+neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression ofCalcbandNmu, Dogiel type II morphology and AH-type electrophysiology andIHcurrent. Optogenetic activation ofCdh6+sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated currentIHdisrupts 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 SummaryIntrinsic sensory neurons of the enteric nervous system in the mouse distal colon exclusively express synaptic cell adhesion moleculesCdh6andCdh8,evoke retrograde colonic motor complexes (CMCs) when stimulated, and possess rhythmicity-associatedIHcurrent, which is necessary for the production of spontaneous CMCs.