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Neural Dynamics Underlying Feeding

喂养背后的神经动力学

基本信息

批准号：
10616817
负责人：
Zachary A. Knight
金额：
$ 50.98万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-20 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10616817
关键词：
Abdomen Ablation Address Animals Behavior Bite Blood Body Weight Brain Brain Stem Brain region Calcium Chemicals Cholecystokinin Consumption Cues Decerebration procedure Dependence Diet Eating Elements Feedback Feeding behaviors Food Gastrointestinal tract structure Hormonal Hormones Infusion procedures Ingestion Intestines Knowledge Learning Liquid substance Measures Methods Mus Nature Neurons Neurosciences Nucleus solitarius Nutrient Obesity Operative Surgical Procedures Optics Oral Pattern Pharmacology Phase Physiology Process Prosencephalon Rattus Regulation Reporting Satiation Signal Transduction Stimulus Stomach Stretching Structure System Taste Blindness Taste Perception Testing Time Viscera Visceral awake cell type conditioning experimental study feeding food consumption gastrointestinal in vivo mechanical signal neural neural circuit neuronal patterning noradrenergic optogenetics response sham feeding

项目摘要

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.

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。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neural circuits underlying thirst and fluid homeostasis.

DOI：
10.1038/nrn.2017.71
发表时间：
2017-08
期刊：
Nature reviews. Neuroscience
影响因子：
0
作者：
Zimmerman CA;Leib DE;Knight ZA
通讯作者：
Knight ZA

Making sense of the sensory regulation of hunger neurons.

DOI：
10.1002/bies.201500167
发表时间：
2016-04
期刊：
BioEssays : news and reviews in molecular, cellular and developmental biology
影响因子：
0
作者：
Chen Y;Knight ZA
通讯作者：
Knight ZA

Layers of signals that regulate appetite.

DOI：
10.1016/j.conb.2020.03.007
发表时间：
2020-10
期刊：
Current opinion in neurobiology
影响因子：
5.7
作者：
Zimmerman CA;Knight ZA
通讯作者：
Knight ZA

A Spotlight on Appetite.

DOI：
10.1016/j.neuron.2018.01.050
发表时间：
2018-02-21
期刊：
Neuron
影响因子：
16.2
作者：
Beutler LR;Knight ZA
通讯作者：
Knight ZA

Identification of preoptic sleep neurons using retrograde labelling and gene profiling.

DOI：
10.1038/nature22350
发表时间：
2017-05-25
期刊：
Nature
影响因子：
64.8
作者：
Chung S;Weber F;Zhong P;Tan CL;Nguyen TN;Beier KT;Hörmann N;Chang WC;Zhang Z;Do JP;Yao S;Krashes MJ;Tasic B;Cetin A;Zeng H;Knight ZA;Luo L;Dan Y
通讯作者：
Dan Y