UV to blue neuronal phototransduction mechanisms

紫外到蓝色神经元光转导机制

• 批准号: 10621560
• 负责人: Todd C Holmes
• 金额: $ 52.05万
• 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 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621560
• 关键词: Aedes; Agriculture; Anopheles gambiae; Arousal; Behavior; Behavior Control; Behavioral; Biological; Biological Assay; Brain; Cells; Color Visions; Complex; Crying; Culicidae; Custom; Devices; Disease Vectors; Drosophila genus; Economics; Electrophysiology (science); Environment; Eye; Flavin-Adenine Dinucleotide; Friends; G-Protein Signaling Pathway; Genetic; Goals; Health; Human; Image; Insect Control; Insecta; Light; Measures; Mediating; Molecular Genetics; Mosquito Control; Neurons; Opsin; Output; Oxidation-Reduction; Pesticides; Phototransduction; Physiological; Research; Rhodopsin; Signal Transduction; System; Time; Vector-transmitted infectious disease; Vision; Visual; behavioral response; chromophore; combat; cryptochrome; design; fighting; fly; hazard; human disease; in vivo; innovation; instrumentation; novel; response; vector-borne

Many insects pose major health and economic hazards to humans as common disease vectors and agricultural pests. Almost all of our present understanding of insect phototransduction is based on opsin-based photoreception in eyes that mediate image forming vision. My lab has recently discovered two additional phototransduction mechanisms in Drosophila. Cryptochrome (CRY) and Rhodopsin 7 (Rh7) expressed in central brain neurons mediate rapid onset sustained electrophysiological responses in these neurons. CRY and Rh7 light signaling underlie a novel form of non-image forming vision that strongly modulates complex time-of-day dependent insect behavioral responses to light, including avoidance/attraction behavioral choice between light and shade and light evoked arousal. While CRY's mechanism of action is due to light evoked redox state changes of its flavin adenine dinucleotide (FAD) chromophore and Rh7's mechanism of action is through a G- protein signaling pathway, they physiologically interact and may form the basis of a true color vision system for non-image forming vision that discerns specific light spectra. We have extended our study of non-image forming vision to harmful nocturnal Anopheles gambiae and diurnal Aedes aegypti mosquitoes and find that CRY1s mediate very distinct time-of-day dependent species specific behavioral light responses in these mosquitp-o important disease vectors. Remarkably, nocturnal and diurnal mosquito CRY1s confer mosquito species specific behavioral effects when expressed in all CRY expressing cells in a cry-null Drosophila genetic background and nocturnal mosquito CRY1 is significantly more light sensitive than diurnal mosquito CRY1 measured by multiple behavioral and electrophysiological assays. We will determine the detailed mechanisms that confer species specific physiological and behavioral light responses for flies and mosquitoes and other insects using a highly sensitive electrophysiological assay that we have developed that will allow us to accurately measure redox state changes and biological outputs for light sensitive CRYs and functional interactions between CRYs and Rh7, in combination with behavioral analysis. Our custom designed instrumentation allows us to examine CRY spectrally driven redox state changes in vivo. Present insect control strategies rely heavily on highly toxic pesticides. A far more environmentally friendly alternative is to make use of light-based behavioral manipulation of insects in a species specific fashion to attract harmful insect species to traps or to repel them away from human habitation. The goal of our research to form a rational basis for designing innovative new LED devices for species-specific harmful insect control in the ongoing fight against vector-borne diseases.

许多昆虫作为常见的疾病媒介对人类构成重大的健康和经济危害， 农业害虫目前我们对昆虫光转导的认识几乎都是基于视蛋白的 眼睛的光感受，调节图像形成视觉。我的实验室最近发现了另外两个 果蝇的光传导机制隐花色素（CRY）和视紫红质7（Rh 7）在中央 脑神经元介导这些神经元中的快速发作持续电生理反应。CRY和Rh 7 光信号是一种新的非图像形成视觉形式的基础，它强烈地调节复杂的时间 依赖性昆虫对光的行为反应，包括对光之间的回避/吸引行为选择 阴影和光线会唤起性欲而CRY的作用机制是由于光诱发的氧化还原状态 其黄素腺嘌呤二核苷酸（FAD）发色团的变化和Rh 7的作用机制是通过一个G- 蛋白质信号通路，它们在生理上相互作用，并可能形成一个真正的彩色视觉系统的基础， 一种非成像的视觉，它能辨别特定的光谱。我们已经扩展了我们对非成像的研究 视觉有害的夜间冈比亚按蚊和白天埃及伊蚊蚊子，并发现， 介导非常不同的时间的一天依赖物种的具体行为光反应，在这些蚊子-o 重要的疾病媒介。值得注意的是，夜间和白天活动的蚊子叮咬赋予蚊子物种特异性 当在cry-无效果蝇遗传背景中的所有CRY表达细胞中表达时的行为效应， 通过多重测量，夜间蚊子E11比白天蚊子E11对光的敏感性明显更高。 行为和电生理测定。我们将确定赋予物种的详细机制 使用高强度的荧光灯， 我们开发的灵敏的电生理学测定方法，使我们能够准确地测量氧化还原状态 光敏感的Rh 7的变化和生物输出以及Rh 7和Rh 7之间的功能相互作用， 结合行为分析。我们定制设计的仪器允许我们检查CRY 光谱驱动的氧化还原状态在体内变化。目前的昆虫控制策略严重依赖于高毒性的 农药一个更环保的替代方案是利用基于光的行为操纵 以一种特定的方式吸引有害的昆虫种类进入陷阱或将它们从陷阱中赶走。 人类居住。我们研究的目标是为设计创新的新型LED器件提供合理的基础。 在持续防治病媒传播疾病的斗争中，对特定物种的有害昆虫进行控制。

项目成果

Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine.

• DOI: 10.1038/s41398-021-01255-4
• 发表时间: 2021-02-24
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Grieco SF;Qiao X;Johnston KG;Chen L;Nelson RR;Lai C;Holmes TC;Xu X
• 通讯作者: Xu X

Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.

• DOI: 10.1186/s12974-023-02932-5
• 发表时间: 2023-11-15
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3

Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony.

• DOI: 10.1523/jneurosci.3074-19.2021
• 发表时间: 2021-06-16
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Nave C;Roberts L;Hwu P;Estrella JD;Vo TC;Nguyen TH;Bui TT;Rindner DJ;Pervolarakis N;Shaw PJ;Leise TL;Holmes TC
• 通讯作者: Holmes TC

Probing neural circuit mechanisms in Alzheimer's disease using novel technologies.

• DOI: 10.1038/s41380-023-02018-x
• 发表时间: 2023-10
• 期刊: MOLECULAR PSYCHIATRY
• 影响因子: 11
• 作者: Grieco, Steven F.;Holmes, Todd C.;Xu, Xiangmin
• 通讯作者: Xu, Xiangmin

Mosquito cryptochromes expressed in Drosophila confer species-specific behavioral light responses.

• DOI: 10.1016/j.cub.2022.07.021
• 发表时间: 2022-09-12
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Au, David D.;Foden, Alexander J.;Park, Soo Jee;Nguyen, Thanh H.;Liu, Jenny C.;Tran, Mary D.;Jaime, Olga G.;Yu, Zhaoxia;Holmes, Todd C.
• 通讯作者: Holmes, Todd C.