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.

项目总结