Investigating temperature sensitive neural circuits that regulate reproductive dormancy

研究调节生殖休眠的温度敏感神经回路

基本信息

批准号：
10084271
负责人：
Nilay Yapici
金额：
$ 24.6万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-09 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10084271
关键词：
Adaptive Behaviors Adult Aedes Aging Allatostatin Alleles Anatomy Animal Model Animals Behavior Behavioral Biology Bioluminescence Brain Cells Circadian Rhythms Climate Collaborations Communicable Diseases Culicidae Dengue Fever Development Developmental Process Disease Disease Vectors Drosophila genus Drosophila melanogaster Environment Environmental Risk Factor Female Female sterility Fertility Food Foundations Functional Imaging Genes Genetic Genetic Models Genetic Screening Goals Head Homeostasis Hormonal Hormones Insect Control Insecta Investigation Knock-in Label Light Maintenance Mammals Mediating Metabolic Metabolism Methods Modeling Modification Molecular Monitor Nervous system structure Neurons Neuropeptides Oocytes Oogenesis Ovarian Ovary Peptides Population Population Control Process Production Property Reproduction Reproductive Behavior Research Resistance Signal Transduction Temperature Testing Universities Vectorial capacity Vertebrates West Nile virus Yellow Fever Yellow fever virus base chikungunya circadian circadian pacemaker cold temperature day length drug development egg environmental change experimental study extreme temperature fly genetic approach human disease in vivo insight interest metabolic rate mutant neural circuit neuromechanism novel pathogen prevent receptor relating to nervous system reproductive response senescence transmission process two photon microscopy vector mosquito zika fever

项目摘要

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.

动物神经系统已经进化出物种特异性的适应行为，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，导致食物短缺和不利的热效应。动物必须做出反应环境中的这些热波动是为了维持身体稳态，这对于他们来说至关重要生存。许多动物物种都有能力经历某种类型的程序性休眠以避免这种情况状况。例如，大多数昆虫和一些哺乳动物会对日长急剧减少和/或温度导致发育和繁殖停止，从而保护它们或其后代免遭致命。在这种休眠状态下，通常由寒冷的温度引发，新陈代谢率显着降低，并且发育过程减慢。尽管对休眠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来减少新陈代谢率和生殖潜力是有限的。尤其是我们仍然不知道分子和神经调节温度敏感神经元兴奋性和抑制性传递变化的机制在环境热波动期间。在这里，我们建议使用遗传上易于处理的模式生物——果蝇（Drosophila melanogaster）来研究温度敏感的神经回路会根据寒冷的温度而改变活动并触发生殖休眠。果蝇是研究神经系统如何应对不良反应的绝佳模型环境条件，因为苍蝇大脑中的神经元比脊椎动物少 1000 倍，但它们仍然表现出温度特定的行为。此外，果蝇神经系统更容易受到遗传影响。修改、解剖学研究和监测行为动物中大量神经元的活动。我们的初步结果表明，大脑中存在神经肽 Allatostatin C (AstC) 及其受体 (AstC-R2) 可能是在寒冷气温和短日照长度下触发生殖休眠的关键因素。在在这个项目中，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，我们将在体内捕获AstC和AstC-R2神经元的活动，并观察它们如何根据温度和日光水平的变化而改变活动。最后我们来测试一下该功能是否可用 AstC-R2 在黄热病蚊子埃及伊蚊中是保守的。我们的成果不仅将有助于对调节昆虫生殖休眠的神经机制有基本的了解，但也将确定开发可控制昆虫种群（尤其是携带疾病）的药物的新目标野外的蚊子。