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。相关的感官刺激经外周受体转化为电信号，形成对外部世界的内部表征。机体内部生理状态对感觉表征的塑造可能是提供行为灵活性的重要机制。特别是，饥饿调节大多数动物的摄食行为以维持能量稳态。尽管嗅觉对食物质量的感知做出了重要贡献，但人们对饥饿如何改变嗅觉表征知之甚少。本研究的重点是研究饥饿在早期嗅觉加工中的调节作用。拟议的实验将在果蝇身上进行，果蝇是一种具有解剖学上简单的嗅觉系统的生物，可以进行分子和遗传操作、光学成像技术和行为分析。本文研究了胰岛素在早期嗅觉系统中是一个全局饱腹信号的假设，并且胰岛素和局部神经肽信号在特定的感觉神经元中被整合，从而使嗅觉敏感性的饥饿调节成为可能。这些实验的目的是：1)评估胰岛素是饥饿调节的全球代谢信号的假设；2)研究局部sNPF（果蝇中NPY的同系物）信号在饥饿依赖性突触前促进中的作用；3)研究局部速激肽信号在饥饿依赖性突触前抑制中的作用。有充分的证据表明，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，这一概念对于在很大一部分人群中似乎不可阻挡的肥胖流行趋势的治疗干预具有潜在的意义。

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.