Neural Dynamics Underlying Feeding

项目摘要 这项建议研究了控制饱腹感的机制。这是生理学中的一个基本问题。 而且还与肥胖有关，因为膳食大小是总食物摄入量的重要决定因素。这个 孤束尾侧核(CNTS)含有终止进食的关键神经回路。这些电路 整合支配腹部内脏的迷走神经传入以及荷尔蒙和 营养信号，以触发终止喂食。虽然碳纳米管的细胞类型早已被研究 通过各种方法，它们在行为过程中的自然活动模式几乎是完全未知的。 解决这一知识差距将揭示调控碳纳米管神经元的关键信号的性质 正常摄食，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，我们开发了记录自由细胞中碳纳米管神经元活动的方法 并研究了它们在进食过程中的动态以及对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 活体内的电路。在目标1和目标2中，我们在胃肠道的不同阶段操纵输入，并衡量这一点 改变喂食过程中碳纳米管的动态。在目标3中，我们使用有针对性的光遗传操作来促进或阻止 这些神经元的自然活动模式的要素，并测量这如何改变食物摄入量和膳食 微观结构。总之，这些实验将揭示尾部脑干如何动态整合 不同的输入，以实现对喂食行为的时刻控制。

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.