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.

动物神经系统具有进化的物种特定的自适应行为，使他们能够应对 不利的环境条件。例如，在温带气候下，冬季的开始标志着急剧下降 在环境温度下，导致食物稀缺和不良热效应。动物必须回应 这些在其环境中的热波动以维持身体的体内平衡，这对他们来说至关重要 生存。许多动物物种有能力经历某种类型的程序休眠，以避免这种情况 状况。例如，大多数昆虫和一些哺乳动物对白天长度和/或 温度随着发育和繁殖的逮捕，可以保护它们或其后代免受杀伤力。 在这种休眠状态下，通常是由寒冷温度触发的，代谢率显着降低，并且 发展过程放慢了速度。尽管研究了几十年来对休眠的生物学的研究，但我们 了解神经系统如何整合温度和光条件的变化以降低 代谢率和生殖潜力受到限制。特别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播的变化的机制 在环境中的热波动过程中。 在这里，我们建议使用遗传上的模型有机体，即果蝇（果蝇Melanogaster）来研究 温度敏感的神经回路会因寒冷温度而改变活动和触发 生殖休眠。苍蝇是研究神经系统如何应对不良的绝佳模型 环境条件，因为苍蝇在大脑中的神经元比脊椎动物少1000倍，但它们是 仍然显示特定温度的行为。此外，蝇神经系统更容易成为遗传 修改，解剖研究和监测行为动物中大量神经元种群的活性。 我们的初步结果表明，脑中神经肽，Allatostatin C（ASTC）及其受体（ASTC-R2） 可能是在寒冷温度和短期内触发生殖休眠的关键参与者。在 该项目，我们将首先确定ASTC和ASTC-R2的神经回路，以调节生殖 苍蝇的休眠。接下来，我们将在体内捕获ASTC和ASTC-R2神经元的活性，并观察它们如何 因温度和日光水平的变化而改变活动。最后，我们将测试功能是否 ASTC-R2的of在黄热病蚊子埃及埃及。我们的结果不仅会为 对调节昆虫生殖休眠的神经机制的基本理解，但也将确定 开发可以控制昆虫种群的药物的新目标，尤其是携带的疾病 荒野中的蚊子。