Mechanism and Modulation of the homeostatic setpoint for protein feeding

蛋白质喂养稳态设定点的机制和调节

基本信息

批准号：
10678640
负责人：
Qili Liu
金额：
$ 46.85万
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：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10678640
关键词：
Action Potentials Address Adult Animals Astrocytes Behavior Behavior assessment Biological Models Brain Calcium Signaling Cell Communication Cells Consumption Dedications Dendrites Drosophila genus Electrophysiology (science)Feeds Female Food Fortified Food Functional Imaging Future Genetic Genetic Screening Goals Growth Hour Human Hunger Immunohistochemistry Impairment Insulin Insulin Receptor Intake Investigation Macronutrients Nutrition Measures Mediating Membrane Membrane Potentials Modeling Molecular Monitor Neuroglia Neurons Partner in relationship Pathway interactions Peptides Physiological Process Production Proteins RNA interference screen Rest Set protein Signal Transduction Sleep Social Interaction Starvation Synapses System Testing Translating Water behavior measurement behavioral study dietary egg feeding fly genetic analysis in vivo imaging insight insulin signaling interdisciplinary approach model organism motivated behavior neural circuit neuronal circuitry novel patch clamp pointed protein pregnant protein intake sensor sex tool transcriptome sequencing

项目摘要

Project Summary All animals share motivated behaviors to fulfill their basic needs for survival, including food, water, sleep, and social interactions, etc. The homeostatic regulatory system energizes behaviors to defend a target level for these needs (the homeostatic setpoint). For example, human adults, on average, aim to sleep 7-8 hours daily. What defines the homeostatic setpoint and how is it modulated remain unanswered questions for all motivated behaviors. Do dedicated neural circuits exist that determine the setpoint? How are changes in physiological needs detected and translated into modified setpoints? These questions have been difficult to address, largely due to a lack of simple manipulations that rapidly and profoundly change the homeostatic setpoints. Protein is a crucially important macronutrient, and behavioral studies indicate that a wide range of species, including humans, seek to consume a fixed amount of protein: the protein intake target. In Drosophila fruit flies, mating induces a robust increase for the consumption of protein-enriched food in pregnant female flies, due to the greater need for protein in egg production. That change in needs rapidly reset the protein intake target and thus provides an elegant model to study the homeostatic setpoint for motivated behaviors. Using Drosophila, we recently identified and characterized the first neural circuit encoding protein-specific hunger. In this proposed study, we seek to delineate the circuit and molecular mechanisms underlying the determination and modulation of the protein intake setpoint. Specifically, we plan to 1) test the hypothesis that the protein intake setpoint is encoded in the hunger neurons by the membrane excitability; 2) identify the neural circuit feeds into the hunger neurons and resets the protein intake target; and 3) elucidate the molecular sensors detecting the changes of protein needs. To achieve these goals, we will employ a multidisciplinary approach, including large-scale genetic analyses, quantitative behavioral measurements, immunohistochemistry, patch-clamp electrophysiology, and functional imaging. These investigations will shed light on the fundamental principles underlying the organization and modulation of homeostatic setpoint for motivated behaviors.

项目概要所有动物都有共同的动机行为来满足其生存的基本需求，包括食物、水、睡眠和社交互动等。稳态调节系统激发行为以捍卫这些需求的目标水平（稳态设定点）。例如，平均而言，成年人的目标是每天睡眠7-8小时。什么定义了稳态设定点以及如何调节它仍然存在所有动机行为的未解答问题。是否存在专用的神经回路来决定设定点？如何检测生理需求的变化并将其转化为修改后的设定值？这些问题很难解决，很大程度上是由于缺乏简单的操作快速而深刻地改变体内平衡设定点。蛋白质是一种至关重要的常量营养素，行为研究表明，包括人类在内的许多物种都试图食用固定蛋白质量：蛋白质摄入目标。在果蝇中，交配会产生强大的怀孕雌性果蝇对富含蛋白质的食物的消耗增加，因为需要更大用于鸡蛋生产中的蛋白质。需求的变化迅速重置了蛋白质摄入目标，从而提供了一个优雅的模型来研究动机行为的稳态设定点。使用果蝇，我们最近发现并描述了第一个编码蛋白质特异性饥饿的神经回路。在这个拟议的研究，我们试图描绘潜在的电路和分子机制蛋白质摄入设定点的确定和调节。具体来说，我们计划 1) 测试假设蛋白质摄入设定点由膜编码在饥饿神经元中兴奋性； 2）识别饥饿神经元的神经回路并重置蛋白质摄入量目标; 3）阐明检测蛋白质需求变化的分子传感器。达到为了实现这些目标，我们将采用多学科方法，包括大规模遗传分析，定量行为测量、免疫组织化学、膜片钳电生理学和功能成像。这些调查将揭示潜在的基本原则组织和调节动机行为的稳态设定点。