Gomez-Frittelli Julieta, Devienne Gabrielle, Travis Lee, Kyloh Melinda A, Duan Xin, Hibberd Tim J, Spencer Nick J, Huguenard John R, Kaltschmidt Julia A
Department of Chemical Engineering, Stanford University; Stanford, CA, USA.
Wu Tsai Neurosciences Institute, Stanford University; Stanford, CA, USA.
bioRxiv. 2024 Dec 20:2024.08.06.606748. doi: 10.1101/2024.08.06.606748.
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, and , specific to sensory neurons in the mouse colon. We show that neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression of and , Dogiel type II morphology and AH-type electrophysiology and current. Optogenetic activation of sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated current 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.
内在感觉神经元是肠神经系统（ENS）的重要组成部分，在胃肠道蠕动和消化中起关键作用。肠神经系统中的神经元亚型已通过其电生理特性、形态以及特征性标志物（特别是神经递质和神经肽）的表达来区分。在此，我们研究了突触细胞粘附分子作为肠神经系统中新型细胞类型标志物。我们的研究确定了小鼠结肠中感觉神经元特有的两种II型经典钙粘蛋白。我们发现这些神经元表现出肠感觉神经元的所有其他区分特征，包括特定标志物的表达、多极II型形态以及AH型电生理和特定电流。结肠远端这些感觉神经元的光遗传学激活引发逆行性结肠运动复合体（CMC），而对与节律相关电流的药理学阻断则破坏了CMC的自发产生。这些发现首次证明了对单一神经化学和功能类别的肠神经元进行选择性激活，并证明了感觉神经元在CMC产生中的功能及关键作用。
