Gomez-Frittelli Julieta, Devienne Gabrielle Frederique, 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, United States.
Wu Tsai Neurosciences Institute, Stanford University, Stanford, United States.
Elife. 2025 Apr 7;13:RP101043. doi: 10.7554/eLife.101043.
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,在胃肠道运动和消化中起关键作用。ENS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(尤其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ENS中新型细胞类型标志物。我们的工作鉴定出两种II型经典钙粘蛋白,它们在小鼠结肠中对感觉神经元具有特异性。我们表明,这些神经元表现出肠感觉神经元的所有其他区分性分类,包括[具体分子名称1]和[具体分子名称2]的标志物表达、多极II型形态以及AH型电生理和[具体电流名称]电流。远端结肠中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(CMCs),而对与节律相关电流[具体电流名称]的药理学阻断会破坏CMCs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的选择性激活,并证明了感觉神经元在CMCs产生中的功能和关键作用。