The neurotransmitter for calorie

项目摘要/摘要 摄食的主要动机是从营养中获取能量。因此，保持体重依赖于 根据认识到营养价值的回路来指导食物的摄入量。肠道的感觉细胞， 肠内分泌细胞，通过荷尔蒙与大脑沟通，在数十分钟内调节食物摄入量，以 几个小时。2018年，我们发现肠内分泌细胞的一部分与迷走神经进行突触接触 很有胆量。我们将这些突触相连的细胞命名为神经足细胞。神经足细胞传达 使用谷氨酸在60毫秒内将十二指肠中的碳水化合物存在到迷走神经 神经传递。然而，谷氨酸编码的信息是未知的。此应用程序测试 假设谷氨酸从肠道到迷走神经的神经传递编码了 营养素。这一假设将在两个具体目标上得到检验。特殊目标1将使用有机化合物(“迷你肠道”)和 小鼠肠内分泌细胞培养以检测谷氨酸对营养刺激的反应。我们 假设从肠内分泌细胞释放的谷氨酸编码营养价值，基于单位 由营养素(即千卡路里)提供的能量，而不是常量营养素含量。因此，我们预测 谷氨酸将以千卡依赖的方式释放，而不是大量营养素依赖的方式。 特殊目的2将在体内使用转基因小鼠迷走神经结节神经节的多光子钙成像 在迷走神经结节神经元中表达钙指示剂GCaMP6。迷走神经细胞的单细胞分辨 活动将被记录下来，以响应营养输送到十二指肠。如果神经足细胞释放谷氨酸 传达关于能量价值的特定信息，而不是常量营养素含量，然后分离 等量卡路里的大量营养素应该刺激重叠的迷走神经元群。通过定义 肠道到迷走神经谷氨酸能信号的功能相关性，这些研究将提供新的基础 肠道-大脑交流的生物学。这项工作将为新药治疗提供新的可能途径。 营养摄入相关疾病的治疗，即肥胖。

PROJECT SUMMARY/ABSTRACT The main motivation to feed is to obtain energy from nutrients. Thus, the maintenance of body weight depends upon circuits which recognize the value of nutrients to guide food intake. The sensory cell of the gut, the enteroendocrine cell, communicates to the brain via hormones to regulate food intake over tens of minutes to hours. In 2018, we discovered that a subset of enteroendocrine cells make synaptic contact with the vagus nerve. We named these synpatically connected cells neuropod cells. Neuropod cells communicate the presence of carbohydrate in the duodenum to the vagus nerve within 60 milliseconds using glutamate neurotransmission. However, the information encoded by glutamate is unknown. This application tests the hypothesis that glutamate neurotransmission from gut to the vagus nerve encodes the energy value of nutrients. This hypothesis will be tested in two specific aims. Specific Aim 1 will use organoid (“mini gut”) and enteroendocrine cell culture from mice to examine glutamate release in response to nutrient stimulation. We hypothesize that glutamate released from enteroendocrine cells encodes nutrient value, based upon the unit energy provided by the nutrient (i.e, kilocalorie) rather than the macronutrient content. Therefore, we predict that glutamate will be released in a kilocalorie-dependent, rather than a macronutrient-dependent manner. Specific Aim 2 will use in vivo multiphoton calcium imaging of the vagal nodose ganglia in transgenic mice which express the calcium indicator GCaMP6s in vagal nodose neurons. Single cell resolution of vagal neuron activity will be recorded in response to nutrient delivery to the duodenum. If neuropod cell glutamate release conveys information specific about energy value, rather than macronutrient content, then separate macronutrients of equal caloric value should stimulate overlapping vagal neuron populations. By defining the functional relevance for rapid gut-to-vagus glutamatergic signaling, these studies will provide new fundamental biology of gut-brain communication. This work will contribute new possible avenues of pharmacotherapies for the treatment of nutrient-intake related disease, namely obesity.