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

• 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
• 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

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.

动物的神经系统已经进化出物种特异性的适应行为，这使得它们能够科普 不利的环境条件。例如，在温带气候中，冬季的开始标志着 在环境温度下，导致粮食短缺和不利的热效应。动物必须对 这些热波动在他们的环境，以维持身体的稳态，这是至关重要的， 生存许多动物物种都有能力经历某种类型的程序化休眠，以避免这种情况。 条件例如，大多数昆虫和一些哺乳动物对日长和/或日照时间的急剧减少作出反应。 在发育和繁殖过程中受到抑制的温度，保护它们或它们的后代免于死亡。 在这种休眠状态下，通常由寒冷的温度触发，代谢率显着降低， 发育过程减慢。尽管对休眠的生物学进行了数十年的研究， 了解神经系统如何整合温度和光照条件的变化， 代谢率和繁殖潜力有限。特别是我们还不知道分子和神经 调节温度敏感神经元兴奋性和抑制性传递变化的机制 在环境中的热波动。 在这里，我们建议使用一种遗传学上易于处理的模式生物--果蝇（Drosophila melanogaster）来研究 对温度敏感的神经回路，其响应于寒冷的温度和触发而改变活动 生殖休眠苍蝇是研究神经系统对不良反应反应的极好模型 环境条件，因为苍蝇在大脑中的神经元比脊椎动物少1000倍，但它们 仍然显示出温度特异性行为。此外，果蝇神经系统更容易遗传 修改，解剖学研究和监测行为动物中大量神经元的活动。 我们的初步研究结果表明，脑中的一种神经肽，Allatostatin C（AstC）及其受体（AstC-R2）， 可能是在低温和短日照条件下引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，并观察它们如何在体内表达。 改变活动以响应温度和日光水平的变化。最后，我们将测试函数是否 AstC-R2在黄热病蚊子埃及伊蚊中是保守的。我们的成果不仅有助于 对调节昆虫生殖休眠的神经机制有基本的了解， 开发控制昆虫种群特别是疾病携带的药物的新目标 野外的蚊子