UV to blue neuronal phototransduction mechanisms

紫外到蓝色神经元光转导机制

• 批准号: 10388927
• 负责人: Todd C Holmes
• 金额: $ 5.5万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10388927
• 关键词: Arousal; Behavior; Behavioral; Biology; Brain; Cells; Complex; Coupled; Couples; Culicidae; Drosophila genus; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Image; Insect Control; Insecta; Invertebrates; Lateral; Light; Membrane; Membrane Potentials; Molecular Genetics; Monitor; Neurons; Opsin; Oxidation-Reduction; Pathway interactions; Photoreceptors; Phototransduction; Physiology; Reaction Time; Research; Resolution; Retina; Rhodopsin; Signal Transduction; Synapses; System; Time; Viola; Voltage-Gated Potassium Channel; Work; base; behavioral response; circadian; cryptochrome; fly; improved; novel; preference; sensor; ultraviolet

Project Summary Cryptochrome (CRY) transduces ultraviolet and blue wavelength light to rapid changes in neuronal membrane potential of lateral ventral circadian/arousal neurons in Drosophila brains by a redox based mechanism via voltage-gated K+ channel beta subunits that express a functional redox sensor that couples light activated CRY to depolarization of the neuronal membrane. Recently, we found that Rhodopsin 7 (Rh7) is an extra- retinal opsin that also expresses in the lateral ventral neurons and transduces violet light to depolarization and increased neuronal firing rate. Light activated Rh7 couples to multiple G-protein pathways. Thus, we have contributed to the discovery of two novel phototransduction that occur in central brain neurons. CRY and Rh7 interact in the lateral ventral neurons, which receive a third photic input synaptically from external photoreceptors. This raises a new set of questions of signaling interactions between redox-based CRY and a G protein-coupled opsin in the same neurons along with further modulation from light driven synaptic inputs. Using an integrative approach based on powerful molecular genetics and behavioral analysis and physiology, we find that CRY expressed in fly neurons regulates UV phototaxis and other light driven behaviors including executive choice. Our most recent work shows that these signaling mechanisms that drive complex light response behaviors are highly sensitive to circadian time of day effects, even diurnal vs. nocturnal preferences. The interactions between CRY and Rh7 provide precise time-of-day information to flies, which we can monitor by circadian whole circuit imaging at single cell resolution. The opportunities are enormous because heretofore, our understanding of short wavelength light sensing in invertebrates, including harmful insects such as mosquitoes has been limited to retinal opsin-based phototransduction. We propose to determine how these short wavelength phototransduction systems converge to a small number of neurons to drive light responses and time of day behavior in flies and mosquitoes. Our research provides new opportunities to improve light control of insects by understanding the fundamental biology of novel redox and G-protein based light signaling mechanisms.

项目概要 隐花色素 (CRY) 将紫外线和蓝色波长的光转变成神经元膜的快速变化 通过基于氧化还原的机制，果蝇大脑侧腹侧昼夜节律/唤醒神经元的潜力 电压门控 K+ 通道 β 亚基，表达耦合光激活的功能性氧化还原传感器 CRY 导致神经元膜去极化。最近，我们发现视紫红质 7 (Rh7) 是一种额外的 视网膜视蛋白也在外侧腹侧神经元中表达，并将紫光转变成去极化和 神经元放电率增加。光激活的 Rh7 与多种 G 蛋白途径偶联。因此，我们有 有助于发现中枢脑神经元中发生的两种新型光转导。 CRY和Rh7 在侧腹神经元中相互作用，该神经元从外部突触接收第三个光输入 光感受器。这提出了基于氧化还原的 CRY 和基于氧化还原的 CRY 之间的信号相互作用的一系列新问题。 同一神经元中的 G 蛋白偶联视蛋白以及光驱动突触输入的进一步调制。 使用基于强大的分子遗传学、行为分析和生理学的综合方法， 我们发现果蝇神经元中表达的 CRY 调节紫外线趋光性和其他光驱动行为，包括 行政选择。我们最近的工作表明，这些驱动复杂光的信号机制 反应行为对昼夜节律的影响高度敏感，甚至对白天与夜间的偏好也高度敏感。 CRY 和 Rh7 之间的相互作用为果蝇提供了精确的时间信息，我们可以监控这些信息 通过单细胞分辨率的昼夜节律全电路成像。机会是巨大的，因为 迄今为止，我们对无脊椎动物（包括有害昆虫，如 因为蚊子仅限于基于视网膜视蛋白的光转导。我们建议确定如何这些 短波长光转导系统汇聚到少量神经元以驱动光响应 以及苍蝇和蚊子一天中不同时间的行为。我们的研究为改善光线提供了新的机会 通过了解新型氧化还原和基于 G 蛋白的光信号传导的基本生物学来控制昆虫 机制。