Investigating temperature sensitive neural circuits that regulate reproductive dormancy

动物神经系统进化出物种特有的适应行为，使它们能够应对 不利的环境条件。例如，在温带气候中，冬季的到来标志着急剧下降。 环境温度下降，导致粮食短缺和不利的热效应。动物必须对 环境中的这些热波动，以维持身体的动态平衡，这对他们的 生死存亡。许多动物物种都有能力经历某种类型的程序化休眠来避免这种 条件。例如，大多数昆虫和一些哺乳动物对日长和/或 温度，在发育和繁殖过程中停止，以保护它们或它们的后代免受死亡。 在这种通常由寒冷温度触发的休眠状态中，代谢率显著降低， 发育过程变慢了。尽管对休眠的生物学进行了数十年的研究，我们的 了解神经系统如何整合温度和光照条件的变化以减少 代谢率和生殖潜力有限。尤其是我们还不知道分子和神经 温度敏感神经元兴奋性和抑制性传递变化的调控机制 在环境中的温度波动期间。 在这里，我们建议使用一种遗传上易驯化的模式生物--苍蝇(Drophila Blackogaster)--来研究 对温度敏感的神经回路，改变活动以响应寒冷的温度并触发 生殖休眠。苍蝇是研究神经系统如何应对不良反应的极佳模型。 环境条件，因为苍蝇大脑中的神经元比脊椎动物少1000倍，但它们 仍然显示特定于温度的行为。此外，苍蝇的神经系统更容易获得基因 修改、解剖学研究和监测动物行为中大量神经元的活动。 我们的初步结果表明，大脑中的神经肽Allatostatin C(ASTC)及其受体(ASTC-R2) 可能是在寒冷的温度和短白天触发生殖休眠的关键因素。在……里面 在这个项目中，我们将首先确定ASTC和ASTC-R2作用于调节生殖的神经回路 苍蝇的休眠状态。接下来，我们将捕捉体内ASTC和ASTC-R2神经元的活动，并观察它们是如何 改变活动以适应温度和日光水平的变化。最后，我们将测试该函数是否 ASTC-R2基因在黄热病蚊虫埃及伊蚊体内保守。我们的结果不仅将有助于 基本了解昆虫生殖休眠的神经调节机制，但也将识别 开发可控制昆虫种群特别是携带疾病的药物的新靶点 野外的蚊子。

Animal nervous systems have evolved species specific adaptive behaviors which allows them to cope with adverse environmental conditions. For example, in temperate climates, the onset of winter marks a steep decline in environmental temperatures, leading to food scarcity and adverse thermal effects. Animals must respond to these thermal fluctuations in their environment in order to maintain body homeostasis which is critical for their survival. Many animal species have the ability to undergo some type of programmed dormancy to avoid such conditions. For example, most insects and some mammals respond to a sharp decrease in day length and/or temperature with an arrest in development and reproduction that protects them or their progeny from lethality. During this dormant state, often triggered by cold temperatures, metabolic rate is significantly decreased and developmental processes are slowed down. Despite decades of research on the biology of dormancy, our understanding of how the nervous system integrates changes in temperature and light conditions to decrease metabolic rate and reproductive potential is limited. Especially we still do not know the molecular and neural mechanisms that regulate the changes in excitatory and inhibitory transmission of temperature sensitive neurons during thermal fluctuations in the environment. Here, we propose to use a genetically tractable model organism, the fly (Drosophila melanogaster), to investigate temperature sensitive neural circuits that change activity in response to cold temperatures and trigger reproductive dormancy. Flies are an excellent model to investigate how nervous system responds to adverse environmental conditions, because flies have 1000-fold fewer neurons in the brain than vertebrates, and yet they still show temperature specific behaviors. Furthermore, the fly nervous system is more accessible for genetic modifications, anatomical studies and monitoring the activity of large populations of neurons in behaving animals. Our preliminary results suggest that a neuropeptide, Allatostatin C (AstC) and its receptor (AstC-R2) in the brain might be a key player in triggering reproductive dormancy during cold temperatures and short-day lengths. In this project, we will first identify the neural circuits that AstC and AstC-R2 act on to regulate reproductive dormancy in flies. Next, we will capture the activity of AstC and AstC-R2 neurons in vivo and observe how they change activity in response to changes in temperature and day light levels. Last, we will test whether the function of AstC-R2 is conserved in the yellow fever mosquito, Aedes aegypti. Our results will not only contribute to the basic understanding of neural mechanisms regulating reproductive dormancy in insects but also will identify novel targets for the development of drugs that can control insect populations especially disease carrying mosquitoes in the wild.