STUDY OF ODOR PERCEPTION AND APPETITIVE MOTIVATION IN DROSOPHILA - Resubmission -

果蝇气味感知和食欲动机的研究 - 重新提交 -

基本信息

批准号：
9013466
负责人：
PING SHEN
金额：
$ 31.66万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-15 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9013466
关键词：
Acetates Action Potentials Adenylate Cyclase Anosmia Appetitive Behavior Behavior Brain Brain region Cues Desire for food Disease Dopamine Dopamine Receptor Dose Drosophila genus Family Food Functional disorder Genes Genetic Health Horns Individual Insecta Knowledge Larva Lasers Lateral Lesion Mammals Mediating Membrane Potentials Modeling Molecular Motivation Names Nervous system structure Neuraxis Neurobiology Neurons Neuropil Odors Olfactory tubercle Organism Outcome Parkinson Disease Pathway interactions Peptides Perception Process Regulation Rewards Role Secretory Vesicles Shapes Signal Transduction Smell Perception Stimulus Synapses System Testing Transgenic Organisms Validation Vinegar base combinatorial dopaminergic neuron dosage electrical property feeding fly genetic analysis genetic risk assessment insight mRNA Differential Displays member mitral cell nervous system disorder neural circuit neuropathology neuropeptide F neuropeptide Y novel patch clamp piriform cortex postsynaptic receptor relating to nervous system research study response vapor

项目摘要

DESCRIPTION (provided by applicant): Understanding how smell is transformed to behavior remains highly challenging. The higher-order olfactory centers, which are two synapses away from the periphery in insects and mammals, are crucial for interpreting the motivational significance of environmental odor cues. At present, molecular and circuit mechanisms underlying the functioning of higher-order olfactory centers have been rarely explored in any organisms. Genetically tractable Drosophila larvae have a highly evolved nervous system that is yet numerically simple. In this application, we will use the fly larva model to elucidate: 1) how a small subset of dopaminergic neurons postsynaptic to second-order projection neurons (analogous to mitral cells in mammals) receives and processes odor representations; 2) how such DA neurons mediate the transformation of olfactory inputs into motivational values to drive appetite for palatable food. Our recent findings demonstrate that Drosophila larvae fed ad libitum display olfactory reward-driven appetite for palatable food, and this non-homeostatic control mechanism requires the neuropil (named the lateral horn) for higher-order olfactory processing. We have found that a small subset of DA neurons as well as four neuropeptide Y-like NPF-producing neurons project to larval lateral horns, and they mediate the transformation of odor representations to appetitive motivation. This application has three objectives: 1) Functional analyses of dopamine (DA) in reception of appetitive olfactory information; 2) Genetic analysis of a neuropeptide F and other molecular pathways in DA neurons; 3) Functional analyses of DA receptor neurons in transforming odor inputs to appetitive motivation. We expect that the successful outcomes from the proposed studies will provide validations of the fly larva model for elucidating the molecular and neural basis of transformation of odor representations to appetitive motivation. Such knowledge should also provide better understanding of the pathophysiology of appetite-related disorders, and aid the genetic risk assessment for such disorders.

描述（由申请人提供）：了解气味如何转化为行为仍然是高度挑战。高阶嗅觉中心，距离昆虫和哺乳动物的外围两个突触，对于解释环境气味提示的动机意义至关重要。目前，在任何生物体中很少探索高阶嗅觉中心功能的基础的分子和电路机制。遗传上可牵引的果蝇幼虫具有高度进化的神经系统，但在数值上却很简单。在此应用程序中，我们将使用Fly Larva模型来阐明：1）多巴胺能神经元的小子集突触后至二阶投射神经元（类似于哺乳动物中的二尖瓣细胞）接受气味表示； 2）这种DA神经元如何介导嗅觉输入转化为动机价值，以驱动对可口食品的食欲。我们最近的发现表明，果蝇幼虫饲养的杂物表现出对可口食品的嗅觉奖励驱动的食欲，而这种非固定控制机制需要神经皮质（称为外侧角）用于高阶嗅觉处理。我们发现，一小部分DA神经元以及四个神经肽Y样的NPF产生神经元向幼虫侧角项目，它们介导了气味表征转化为食用动机。该应用具有三个目标：1）在接受食用嗅觉信息中多巴胺（DA）的功能分析； 2）DA神经元中神经肽F和其他分子途径的遗传分析； 3）DA受体神经元在将气味输入转化为食用动机中的功能分析。我们预计，提出的研究的成功结果将提供验证幼虫模型，以阐明气味表征转化为食用动机的分子和神经基础。这种知识还应更好地了解与食欲相关疾病的病理生理学，并帮助对此类疾病的遗传风险评估。