胰岛素信号历来被认为是机体能量代谢的系统性调控信号，然而近年来的研究提示，在中枢神经系统中，它可能不仅仅影响发育和营养代谢，而是具有更加复杂和特异的功能。向哺乳动物的脑中灌注胰岛素引起强烈的进食抑制效应，但由于大脑中类胰岛素生长因子或类胰岛素肽及其受体种类繁多、分布广泛，进食调控神经环路又异常复杂，难以全面解析相关的神经通路和分子机制。本实验室前期工作在果蝇中发现了首个蛋白营养特异性感知和进食抑制因子FIT，而它下游主要的效应分子是果蝇脑中表达的三种类胰岛素肽之一。因此，本申请提出，以果蝇高蛋白营养的进食抑制作用为索引，揭示中枢胰岛素信号的特异性释放和被下游神经元特异性识别的神经分子机制。通过遗传学筛选和神经行为学操控相结合，我们已找到了特异性响应高蛋白-胰岛素信号的候选神经元，并计划在此基础上进一步探索其细胞、分子基础，以期揭示出全新的中枢胰岛素信号在行为调控中的特异性信息传递功能。

Insulin-like Signaling (IlS) is always thought to be a systematic signal regulating energy metabolism. Nevertheless, more and more evidences have emerged to suggest that in addition to development and metabolism, IlS may play more complex and special functions in the central nervous system (CNS). Infusion of insulin into the cerebrospinal fluid (CSF) of mammal brains leads to strong inhibition of feeding behavior, while the underlying neural pathways and molecular mechanisms remain to be elucidated. This is partially due to various insulin-like growth factors (IGFs) and insulin-like peptides, as well as their receptors, are widely expressed in the CNS. Furthermore, the neural circuit for regulating feeding behavior is extremely complicated. Our recent work identified the first protein-specific nutrient sensing factor, FIT (Female-specific Independent of Transformer), that suppresses protein intake, specifically. Interestingly, its downstream effector is a Drosophila Insulin Like Peptide (DILP), one of the three that are expressed in the fly brain. Therefore, this application proposes to uncover the molecular and neural mechanisms of the specific release and recognition of CNS IlS by following up the feeding inhibition effect of high protein nutrient in the fruit flies. Utilizing the tools of genetic screen and neuroethology manipulation, we have found candidate neurons that specifically respond to high protein nutrient-induced IlS. From this, we plan to investigate the underlying cellular and molecular basis and aim to uncover novel information transmission function of CNS IlS in regulating animal behavior.