Neural Dynamics Underlying Feeding

项目摘要 这个建议调查的机制，控制饱食。这是生理学中的一个基本问题 而且还与肥胖有关，因为膳食量是总体食物摄入量的重要决定因素。的 孤束尾侧核（cNTS）包含用于进餐终止的关键神经回路。这些电路 整合来自支配腹部内脏的迷走神经传入神经的输入以及循环激素， 营养信号，以触发喂养的终止。虽然cNTS细胞类型已经研究了很长时间， 使用各种方法，它们在行为期间的自然活动模式几乎完全未知。 解决这一知识缺口将揭示在神经元分化过程中调节cNTS神经元的关键信号的性质。 正常进食，这些信号如何整合到特定的细胞类型中，以及它们在过程中如何演变 一顿饭。在初步研究中，我们开发了记录cNTS神经元活动的方法， 行为小鼠，并表征其动力学喂养期间，并在各种内脏刺激的反应。 在这里，我们建议在这些发现的基础上系统地剖析调节cNTS饱腹感的信号 体内电路在目标1和2中，我们操纵胃肠道各个阶段的输入，并测量这是如何实现的。 在进食期间改变cNTS动力学。在目标3中，我们使用靶向光遗传学操作来增强或阻断 这些神经元的自然活动模式的元素，并测量这如何改变食物摄入量和膳食 微观结构总之，这些实验将揭示尾脑干如何动态整合 不同的输入，使每时每刻的喂养行为的控制。

Project Summary This proposal investigates the mechanisms that control satiation. This is a fundamental problem in physiology and also has relevance to obesity, because meal size is an important determinant of overall food intake. The caudal nucleus of the solitary tract (cNTS) contains key neural circuits for meal termination. These circuits integrate input from vagal afferents innervating the abdominal viscera as well as circulating hormonal and nutrient signals in order to trigger the termination of feeding. While cNTS cell types have long been studied using a variety of approaches, their natural activity patterns during behavior are almost completely unknown. Addressing this knowledge gap would reveal the nature of the key signals that regulate cNTS neurons during normal feeding, how these signals are integrated in specific cell types, and how they evolve during the course of a meal. In preliminary studies, we developed methods to record the activity of cNTS neurons in freely behaving mice and characterized their dynamics during feeding and in response to a variety of visceral stimuli. Here we propose to build on these findings to systematically dissect the signals that regulate cNTS satiety circuits in vivo. In Aims 1 and 2, we manipulate inputs at various stages of the GI tract and measure how this alters cNTS dynamics during feeding. In Aim 3, we use targeted optogenetic manipulations to boost or block elements of the natural activity patterns of these neurons and measure how this alters food intake and meal microstructure. Together, these experiments will reveal how the caudal brainstem dynamically integrates diverse inputs to enable the moment-by-moment control of feeding behavior.