Olfactory neuromodulation of visual circuits and behavior

视觉回路和行为的嗅觉神经调节

• 批准号: 10405378
• 负责人: Mark Arthur Frye
• 金额: $ 6.34万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405378
• 关键词: Affect; Aging; Behavior; Biogenic Amines; Biological Models; Brain; Cells; Chemicals; Cognitive; Complex; Couples; Degenerative Disorder; Detection; Disease; Drosophila genus; Functional disorder; Genetic Models; Genetic Techniques; Human; Image; Individual; Lead; Logic; Modality; Molecular; Nervous system structure; Neurons; Norepinephrine; Output; Pathology; Pathway interactions; Perception; Population; Process; Property; Research; Sensory; Signal Transduction; Stimulus; Stroke; Synapses; Traumatic injury; United States; Visual; Writing; brain health; chemical function; cognitive function; disability; fly; functional disability; multimodality; multisensory; neuronal circuitry; neuroregulation; nonhuman primate; optogenetics; public health relevance; relating to nervous system; response; two-photon; virtual reality system; visual processing

Project summary A significant percentage of people in the US suffer from disabilities resulting from traumatic injury, stroke, or degenerative disease which result in enigmatic deficits in cognitive function. Therefore, an understanding of the fundamental properties of neuronal circuits for complex brain function, and how these circuits are modulated by biogenic amines, will sharpen our understanding of the normal brain, thereby highlighting pathology and facilitating treatments. A major function of the brain is to integrate information across sensory modalities to enable sharp and robust perception. The cell-circuit mechanism for how different sensory modalities interact is not well understood. This project will capitalize on the significant experimental advantages of the fruit fly Drosophila to explore the molecular logic and neural connections that produce an elementary form of multisensory integration perception. The fly displays robust multisensory perception, integrating olfactory signals with visual processing to enhance perceptual abilities. Furthermore, sensory circuits have been shown to be under robust neuromodulatory control by biogenic amines. Similar processes have been localized to sub- cortical and cortical pathways in humans and non-human primates. The fly has a numerically compact nervous system, with which highly advanced genetic techniques can be used to identify, manipulate, and record activity from individual neurons and neurosecretory cells, as well as their upstream and downstream synaptic partners and molecular components. The PI hypothesizes that the fly brain couples olfactory sensory detection to visual processing through neuromodulatory cells that carry the chemical equivalent of norepinephrine. The PI will perform two-photon Ca2+ imaging to ‘read’ activity from live flies in response to stimuli the PI has discovered elicit robust multi-modal integration behavior within a virtual reality system. The PI will use optogenetics imaging to ‘write’ signals into these circuit pathways to assess input-output functions from an intact behaving fly.

项目摘要 在美国，很大一部分人患有创伤性残疾， 损伤、中风或退行性疾病，导致认知功能的神秘缺陷。 因此，了解复杂大脑神经元回路的基本特性 功能，以及这些电路是如何被生物胺调节的，将使我们的研究更加清晰。 了解正常的大脑，从而突出病理和促进治疗。 大脑的一个主要功能是整合各种感官形式的信息， 敏锐而有力的感知。不同感觉形态的细胞回路机制 交互作用还没有得到很好的理解。该项目将利用重要的实验性 果蝇的优势，以探索分子逻辑和神经连接， 产生一种多感官整合感知的基本形式。苍蝇表现出健壮的 多感官知觉，整合嗅觉信号与视觉处理，以增强 感知能力此外，感觉回路已经被证明是鲁棒的， 生物胺的神经调节控制。类似的过程已被本地化， 人类和非人类灵长类动物的皮质和皮质通路。苍蝇有一个数字 紧凑的神经系统，高度先进的遗传技术可以用来 识别、操纵和记录单个神经元和神经分泌细胞的活动， 以及它们的上游和下游突触伴侣和分子组分。的PI 假设苍蝇的大脑通过嗅觉感觉检测与视觉处理相结合， 神经调节细胞携带去甲肾上腺素的化学等价物。PI将执行 双光子Ca2+成像，以“读取”活蝇对PI刺激的反应活性， 发现在虚拟现实系统内引发鲁棒的多模态集成行为。的PI 将使用光遗传学成像将信号“写入”这些电路路径，以评估输入输出 一只完好的果蝇的功能