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对于动物生存至关重要。相关的感觉刺激被外周感受器转化为电信号，形成外部世界的内部表征。由机体内部生理状态形成的感觉表征可能是提供行为灵活性的重要机制。特别是，饥饿调节大多数动物的进食行为，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。本研究旨在探讨嗅觉加工早期的饥饿调节机制。拟议的实验将在果蝇中进行，果蝇是一种具有解剖学上简单的嗅觉系统的生物体，可以进行分子和遗传操作，光学成像技术和行为分析。这里概述的实验调查的假设，胰岛素是一个全球性的饱腹感信号在早期的嗅觉系统，胰岛素和本地神经肽信号被整合在特定的感觉神经元，使饥饿调节嗅觉灵敏度。这些实验的目的是：1）评估胰岛素是饥饿调节的全局代谢信号的假设; 2）研究局部sNPF（果蝇中NPY的同源物）信号在饥饿依赖性突触前易化中的作用; 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。有很好的证据表明，这种周围嗅觉系统的饥饿调制存在于脊椎动物系统。外周嗅觉系统的饥饿调节与胰岛素信号传导有关的概念，对于大部分人群中看似不可阻挡的肥胖流行趋势的治疗干预具有潜在意义。

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.