Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Neuroscience and Department of Cell Biology, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, CT 06536, USA.
Cell. 2019 Jan 10;176(1-2):85-97.e14. doi: 10.1016/j.cell.2018.11.023. Epub 2018 Dec 20.
Animals must respond to the ingestion of food by generating adaptive behaviors, but the role of gut-brain signaling in behavioral regulation is poorly understood. Here, we identify conserved ion channels in an enteric serotonergic neuron that mediate its responses to food ingestion and decipher how these responses drive changes in foraging behavior. We show that the C. elegans serotonergic neuron NSM acts as an enteric sensory neuron that acutely detects food ingestion. We identify the novel and conserved acid-sensing ion channels (ASICs) DEL-7 and DEL-3 as NSM-enriched channels required for feeding-dependent NSM activity, which in turn drives slow locomotion while animals feed. Point mutations that alter the DEL-7 channel change NSM dynamics and associated behavioral dynamics of the organism. This study provides causal links between food ingestion, molecular and physiological properties of an enteric serotonergic neuron, and adaptive feeding behaviors, yielding a new view of how enteric neurons control behavior.
动物必须通过产生适应性行为来响应食物的摄入,但肠道-大脑信号在行为调节中的作用还知之甚少。在这里,我们鉴定了参与摄食反应的肠嗜铬神经元中保守的离子通道,并解析了这些反应如何驱动觅食行为的变化。我们发现,线虫中 5-羟色胺能神经元 NSM 作为肠感觉神经元,可急性检测食物的摄入。我们鉴定了新型保守酸感应离子通道(ASICs)DEL-7 和 DEL-3,作为 NSM 活性所必需的 NSM 富集通道,这些通道反过来驱动动物进食时的缓慢运动。改变 DEL-7 通道的点突变会改变 NSM 的动力学和生物体相关的行为动力学。这项研究提供了食物摄入、肠 5-羟色胺能神经元的分子和生理特性以及适应性摄食行为之间的因果关系,为肠道神经元如何控制行为提供了新的视角。