The neurotransmitter for calorie

项目总结/摘要 进食的主要动机是从营养物质中获取能量。因此，维持体重取决于 通过识别营养价值来指导食物摄入的电路。肠道的感觉细胞， 肠内分泌细胞，通过激素与大脑沟通，在数十分钟内调节食物摄入量， 小时在2018年，我们发现肠内分泌细胞的一个子集与迷走神经进行突触接触 神经。我们将这些突触连接的细胞命名为神经足细胞。神经足细胞将 使用谷氨酸盐在60毫秒内将十二指肠中的碳水化合物存在于迷走神经 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 假设从肠道到迷走神经的谷氨酸神经传递编码了 营养素这一假设将在两个具体目标中得到检验。具体目标1将使用类器官（“迷你肠”）， 从小鼠的肠内分泌细胞培养物检测响应于营养刺激的谷氨酸释放。我们 假设肠内分泌细胞释放的谷氨酸编码营养价值，基于单位 由营养素提供的能量（即千卡），而不是常量营养素含量。因此，我们预测 谷氨酸的释放依赖于千卡热量，而不是依赖于大量营养素。 具体目标2将使用转基因小鼠迷走神经结状神经节的体内多光子钙成像 其在迷走神经结状神经元中表达钙指示剂GCaMP 6s。迷走神经元的单细胞分辨 将记录响应于营养物输送到十二指肠的活性。如果神经足细胞释放谷氨酸 传达关于能量值的具体信息，而不是大量营养素含量，然后将 相同热值的大量营养素应刺激重叠的迷走神经元群。通过定义 这些研究与快速肠道至迷走神经谷氨酸能信号传导的功能相关性将提供新的基础知识 肠脑交流的生物学这项工作将为药物治疗提供新的可能途径， 治疗与营养摄入有关的疾病，即肥胖症。

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.