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Coordinating hunger and thirst drives in Drosophila

协调果蝇的饥饿和口渴驱动

基本信息

批准号：
10117259
负责人：
Kristin E Scott
金额：
$ 34.7万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-15 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10117259
关键词：
Affect Animals Behavior Behavioral Behavioral Assay Blood Calcium Cells Complex Consumption Coupled Detection Drosophila genus Drosophila melanogaster Electrophysiology (science)GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Homeostasis Hunger Hypothalamic structure Image Ingestion Ion Channel Mammals Measurement Modeling Molecular Genetics Monitor Nervous system structure Neuromodulator Neurons Neurophysiology - biologic function Neurosciences Nutrient Nutritional Organ Osmolalities Pathway interactions Peptides Regulation Research Sensory Signal Transduction Structure of nucleus infundibularis hypothalami Sucrose System Taste Perception Testing Thirst Time Water Water consumption Work adipokinetic hormone base deprivation drinking feeding food consumption gene function imaging approach imaging study insight mutant neuroregulation response sugar tool

项目摘要

Feeding decisions are tightly regulated based on internal needs. Signals of hunger and thirst are detected by interoceptive neurons that promote specific consumption to restore homeostasis. Although generally considered independently, recent studies have demonstrated that interactions between hunger and thirst drives are important to coordinate competing needs. The aim of this proposal is to examine how food and water consumption is coordinately regulated, using the well developed Drosophila system as a model. These studies will evaluate how multiple internal signals are integrated within a neuron to regulate activity and how the activity of a single set of neurons regulates two opponent behaviors. This research takes advantage of established behavioral assays for water and sucrose consumption in Drosophila, molecular genetics to rapidly manipulate genes and neural function, single-cell electrophysiology for precise measurements of signal integration, and large-scale calcium imaging approaches to study network interactions. Specific Aim 1 will examine how signals of hunger and thirst modulate activity of interoceptive neurons, providing insight into how multiple signals are integrated within a neuron over time. Specific Aim 2 will characterize neurons downstream of the interoceptive neurons to examine how activity is transmitted to circuits to oppositely regulate two behaviors. Specific Aim 3 will determine how interoceptive neurons alter the responses in taste sensorimotor circuits to examine how internal states generate plastic changes in feeding networks. The proposed efforts will determine how internal signals of nutritional state are integrated across time to coordinate feeding decisions. The long-term objective of this work is to provide insight into how neuromodulators regulate circuits and behavior over long timescales, a basic problem in neuroscience relevant across systems.

喂养决定根据内部需求进行严格监管。饥渴的信号是通过内感受神经元检测，促进特定消耗以恢复体内平衡。虽然一般独立考虑，最近的研究表明，饥饿和饥饿之间的相互作用，渴驱力对于协调相互竞争的需求很重要。这项建议的目的是研究食物和以发育良好的果蝇系统为模型，对水分消耗进行协调调节。这些研究将评估多个内部信号如何整合在神经元内以调节活动，以及一组神经元的活动调节两种对立的行为。这项研究利用了在果蝇中建立了消耗水和蔗糖的行为测定，分子遗传学可以快速地操纵基因和神经功能，单细胞电生理学用于精确测量信号整合和大规模钙成像方法来研究网络相互作用。具体目标1将研究饥饿和口渴的信号如何调节内感受神经元的活动，多个信号随时间在神经元内被积分。具体目标2将表征神经元下游的内感受神经元，以检查活动是如何传递到电路，以相反地调节两个行为。具体目标3将确定内感受神经元如何改变味觉感觉运动反应电路来研究内部状态如何在馈电网络中产生塑性变化。拟议的努力将确定营养状态的内部信号如何跨时间整合，以协调喂养决策。这项工作的长期目标是深入了解神经调节剂如何调节回路，长期行为，这是神经科学中与系统相关的基本问题。