Drosophila: Metabolic modulation of olfactory circuit function/ feeding behavior

描述(由申请人提供)：基本生理需求对行为的调节是动物生存所必需的。相关的感觉刺激由外周感受器转化为电信号，形成外部世界的内部表征。通过生物体内部的生理状态塑造感觉表征可能是提供行为灵活性的重要机制。特别是，饥饿调节了大多数动物的摄食行为，以维持能量平衡。尽管嗅觉对食物质量的感知有重要贡献，但人们对饥饿如何改变嗅觉表现知之甚少。本研究的重点是研究早期嗅觉加工中的饥饿调节。拟议的实验将在果蝇身上进行，这是一种在解剖学上具有简单嗅觉系统的有机体，可以接受分子和遗传操作、光学成像技术和行为分析。这里概述的实验研究了胰岛素是早期嗅觉系统中的全局饱腹感信号，以及胰岛素和局部神经肽信号在特定的感觉神经元上整合以实现嗅觉敏感性饥饿调节的假设。这些实验的目的是：1)评估胰岛素是调节饥饿的全球代谢信号的假设；2)研究局部sNPF(果蝇中NPY的同源物)信号在饥饿依赖的突触前促进中的作用；3)研究局部速激素信号在饥饿依赖的突触前抑制中的作用。有很好的证据表明，这种外周嗅觉系统的饥饿调节存在于脊椎动物系统中。外周嗅觉系统的饥饿调节与胰岛素信号有关的概念，对于在很大比例的人口中似乎无法阻止的肥胖流行趋势的治疗干预具有潜在的意义。 与公共健康相关：肥胖似乎是一种无法遏制的流行病，影响着大量人口。这项研究的工作是试图揭示嗅觉和食欲行为之间的联系的基础科学。定义调节摄食行为的嗅觉回路将创建一个知识库，根据该知识库可以为未来的治疗干预评估潜在的分子靶点。

DESCRIPTION (provided by applicant): The modulation of behavior by basic physiological need is essential for animal survival. Relevant sensory stimuli are transformed by peripheral receptors into electrical signals to form an internal representation of the external world. Shaping sensory representation by internal physiological state of the organism could be an important mechanism to provide behavioral flexibility. In particular, hunger modulates feeding behavior in most animals to maintain energy homeostasis. Despite that olfaction makes important contribution to the perception of food quality, very little is known about how starvation alters olfactory representation. This proposal focuses on studying the hunger modulation in early olfactory processing. The proposed experiments will be carried out in Drosophila, an organism with an anatomically simple olfactory system that is amenable to molecular and genetic manipulations, optical imaging technologies, and behavioral analysis. The experiments outlined here investigate the hypotheses that insulin is a global satiety signal in the early olfactory system, and that both insulin and local neuropeptide signaling are integrated at specific sensory neurons to enable hunger modulation of olfactory sensitivity. The goals of these experiments are: 1) evaluating the hypothesis that insulin is a global metabolic signal for hunger modulation; 2) investigating the role of local sNPF (a homolog of NPY in Drosophila) signaling in starvation-dependent presynaptic facilitation; 3) investigating the role of local tachykinin signaling in starvation-dependent presynaptic inhibition. There is good evidence to suggest that this kind of hunger modulation in peripheral olfactory system is present in vertebrate systems. The notion that hunger modulation at the peripheral olfactory system is linked to insulin signaling has potential implication for therapeutic intervention of the seemingly unstoppable obesity epidemic trend in a large percentage of the population. PUBLIC HEALTH RELEVANCE: Obesity is a seemingly unstoppable epidemic that affects a large population. The work of this proposal is basic science that seeks to reveal the connection between olfaction and appetitive behavior. Defining the olfactory circuit that modulate feeding behavior will create a knowledge base from which potential molecular targets can be evaluated for future therapeutic interventions.