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 -

• 批准号: 8697512
• 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
• 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/8697512
• 关键词: Action Potentials; Adenylate Cyclase; Anosmia; Appetitive Behavior; Behavior; Brain; Brain region; Cells; Cues; Desire for food; Disease; Dopamine; Dopamine Receptor; Dose; Drosophila genus; Family; Food; Functional disorder; Genes; Genetic; 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; amyl acetate; base; combinatorial; dopaminergic neuron; dosage; electrical property; feeding; fly; genetic analysis; genetic risk assessment; insight; mRNA Differential Displays; member; nervous system disorder; neural circuit; neuropathology; neuropeptide F; neuropeptide Y; novel; patch clamp; piriform cortex; postsynaptic; public health relevance; receptor; relating to nervous system; research study; response; vapor

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）：理解气味如何转化为行为仍然极具挑战性。高阶嗅觉中心是昆虫和哺乳动物中远离外围的两个突触，对于解释环境气味线索的动机意义至关重要。目前，在任何生物体中都很少探索高阶嗅觉中心功能的分子和电路机制。遗传上易驯化的果蝇幼虫具有高度进化的神经系统，但在数字上却很简单。在此应用中，我们将使用蝇幼虫模型来阐明：1） 突触后二阶投射神经元（类似于哺乳动物的二尖瓣细胞）的一小部分多巴胺能神经元接收并处理气味表征； 2）这些 DA 神经元如何介导将嗅觉输入转化为动机值，以驱动对美味食物的食欲。我们最近的研究结果表明，随意进食的果蝇幼虫表现出嗅觉奖励驱动的对美味食物的食欲，这种非稳态控制机制需要神经纤维（称为侧角）进行高阶嗅觉处理。我们发现一小部分 DA 神经元以及四个神经肽 Y 样 NPF 产生神经元投射到幼虫侧角，它们介导气味表征向食欲动机的转化。该应用程序具有三个目标：1）多巴胺（DA）在接收食欲嗅觉信息中的功能分析； 2) DA神经元中神经肽F和其他分子通路的遗传分析； 3）DA受体神经元将气味输入转化为食欲动机的功能分析。我们期望所提出的研究的成功结果将为蝇幼虫模型提供验证，以阐明气味表征转化为食欲动机的分子和神经基础。这些知识还应该有助于更好地理解食欲相关疾病的病理生理学，并有助于此类疾病的遗传风险评估。