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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.

项目总结