The efferent synapse in enteroendocrine cells

摘要 今天，人们对肠道到大脑的感觉转导非常着迷。营养素和细菌是已知的 调节行为。然而，大脑如何调节胃肠道感觉功能尚不清楚。 一些行为障碍，如与压力和食欲有关的行为障碍，已被认为与 改变了内脏功能。肠道感觉传导的支柱是支配肠道的神经元。 粘膜和肠内分泌细胞--面向管腔的上皮细胞。当受到刺激时 营养物质，或细菌，它们激发动作电位。我们最近发现，这些细胞与 迷走神经在毫秒内将营养刺激传递到大脑。他们使用谷氨酸来完成这一过程 作为一种神经递质。最近的研究还表明，肠道内分泌细胞的一个子集 分泌的5-羟色胺由交感神经递质去甲肾上腺素激活。我们的预赛 数据显示，这些细胞还接受来自脊髓周围神经元的突触输入。 因此，我们假设脊髓神经元使用去甲肾上腺素作为传出神经递质 调节肠内分泌细胞的感觉功能。在NIH R21研究项目的支持下，我们的 目标是通过1)在体内和体外定义传出突触来剖析这一神经回路；以及2) 建立去甲肾上腺素作为传出神经元到肠内分泌细胞的突触神经递质。 该项目将为了解大脑功能和行为如何改变内脏奠定神经基础。 感官功能。

ABSTRACT Today, there is a fascination with gut-to-brain sensory transduction. Nutrients and bacteria are known to modulate behaviors. However, how the brain modulates gastrointestinal sensory function is unknown. Several behavioral disorders, such as those related to stress and appetite, have been linked with altered visceral function. The pillars of sensory transduction in the gut are the neurons that innervate the mucosa and the enteroendocrine cells — epithelial cells that face the lumen. When stimulated by nutrients, or bacteria, they fire action potentials. We recently discovered that these cells synapse with the vagus nerve to transduce nutrient stimuli to the brain in milliseconds. They do so using glutamate as a neurotransmitter. Recent studies have also shown that a subset of enteroendocrine cells that secrete serotonin are activated by the sympathetic neurotransmitter, norepinephrine. Our preliminary data show that these cells also receive synaptic inputs from peripheral neurons of the spinal cord. Therefore, we hypothesize that spinal neurons use norepinephrine as an efferent neurotransmitter to modulate enteroendocrine cell sensory function. With the support of this NIH R21 research project, our goal is to dissect this neural circuit by 1) defining the efferent synapse both in vivo and in vitro; and 2) establishing norepinephrine as an efferent neuron-to-enteroendocrine cell synaptic neurotransmitter. This project will set the neural basis for understanding how brain function and behaviors alter visceral sensory function.