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造成重大健康和经济危害 农业害虫。我们目前对昆虫光转导的所有理解几乎都是基于视蛋白 眼睛的光接收介导图像形成视觉。我的实验室最近发现了另外两个 果蝇的光转导机制。隐花色素 (CRY) 和视紫红质 7 (Rh7) 在中枢表达 大脑神经元介导这些神经元快速发生持续的电生理反应。 CRY和Rh7 光信号是一种新型非图像形成视觉的基础，它强烈调节一天中复杂的时间 依赖昆虫对光的行为反应，包括光之间的回避/吸引行为选择 阴影和光线会引起兴奋。而CRY的作用机制是由于光诱发的氧化还原态 其黄素腺嘌呤二核苷酸（FAD）发色团的变化和Rh7的作用机制是通过G- 蛋白质信号通路，它们在生理上相互作用，并可能形成真正的色彩视觉系统的基础 辨别特定光谱的非图像形成视觉。我们扩展了非图像形成的研究 对有害的夜间活动冈比亚按蚊和白天活动的埃及伊蚊进行视觉观察，发现 CRY1s 在这些 mosquitp-o 中介导非常独特的依赖于一天中时间的物种特定行为光反应 重要的疾病媒介。值得注意的是，夜间和白天的蚊子 CRY1 赋予蚊子物种特异性 在cry-null果蝇遗传背景下的所有CRY表达细胞中表达时的行为影响 通过多次测量，夜间活动的蚊子 CRY1 比昼间活动的蚊子 CRY1 的光敏感度明显更高。 行为和电生理学测定。我们将确定赋予物种的详细机制 苍蝇、蚊子和其他昆虫的特定生理和行为光反应，使用高度 我们开发的灵敏电生理测定法将使我们能够准确测量氧化还原状态 光敏 CRY 的变化和生物输出以及 CRY 和 Rh7 之间的功能相互作用， 与行为分析相结合。我们定制设计的仪器使我们能够检查 CRY 光谱驱动的体内氧化还原态变化。目前的昆虫控制策略严重依赖剧毒 杀虫剂。一种更环保的替代方案是利用基于光的行为操纵 以特定物种的方式吸引有害昆虫物种到陷阱或将其驱逐 人类居住。我们研究的目标是为设计创新的新型 LED 器件形成合理的基础 在持续对抗媒介传播疾病的过程中进行特定物种的有害昆虫控制。

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

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

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

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.