Neural Mechanisms of Cross-modal Integration in the Fruit Fly

果蝇跨模态整合的神经机制

• 批准号: 1455869
• 负责人: Mark Frye
• 金额: $ 68万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455869&HistoricalAwards=false
• 关键词: Neural; Mechanisms; Cross; modal; Integration

It is scientifically daunting, yet society poses a grand challenge to neuroscientists to discover how complex brain function emerges from the activity patterns of individual neurons and the small interconnected circuits that they form. One important open question is how does the brain integrate different sensory inputs to create a cohesive perception of the world? Neuroscientists have a good understanding that senses are integrated at the cognitive level, for example that the perception of flavor is an integration of taste and smell. But the field has a poor understanding of the underlying mechanism - how circuits of brain cells wire multiple senses together. This project takes an interdisciplinary approach using genetics, live brain imaging, virtual reality behavior and engineering analysis to determine the elemental neural circuit mechanisms by which sensory modalities are integrated for perception. The researchers seek to identify the cellular identity, cell-cell connections, function, and neuro-chemical interactions that link sensory modalities together. For this work, the researchers use a powerful neuro-genetic model system: the fruit fly Drosophila, which exhibits a rich multi-sensory repertoire of behavior in the laboratory, and for which there exists a wealth of molecular-genetic tools to study and manipulate identified neurons and neural circuits. A large body of evidence has demonstrated that in flies olfactory signals boost the strength of visual stabilization reflexes analogous to our own gaze-stabilizing eye movements. The researchers will test the hypothesis that olfactory signaling alters the response strength of neurons within the visual processing pathway, and that olfactory sensory pathways are linked to visual pathways by neurosecretory cells releasing biogenic amines. The researchers make use of virtual reality flight simulators, and live imaging using state-of-the-art multi-photon excitation fluorescence microscopy to genetically target calcium reporters within select interneurons and neuromodulatory circuits innervating the visual regions of the brain. They expect to discover that neurosecretory cells are excited by odor, and release biogenic amines into visual processing centers, which in turn alter the membrane properties and synaptic integration of visual motion circuitry. They expect that genetically silencing these interactions eliminates behavioral responses to visual motion that are well known to be enhanced by simultaneous presentation of odor cues. The project is conceptually linked with an outreach effort to K-12 students by outfitting a Mobile Fly Lab to provide demonstration workshops at local elementary schools.

这在科学上是令人生畏的，但社会对神经科学家提出了一个巨大的挑战，要发现复杂的大脑功能是如何从单个神经元的活动模式和它们形成的相互连接的小回路中产生的。一个重要的悬而未决的问题是，大脑如何整合不同的感官输入，以创造一个有凝聚力的感知世界？神经科学家很好地理解了感官是在认知水平上整合的，例如对味道的感知是味觉和嗅觉的整合。但该领域对潜在的机制--脑细胞回路如何将多种感觉连接在一起--的理解很差。该项目采用跨学科的方法，使用遗传学，活体脑成像，虚拟现实行为和工程分析，以确定感觉模态集成感知的基本神经回路机制。 研究人员试图确定将感觉方式联系在一起的细胞身份，细胞间连接，功能和神经化学相互作用。对于这项工作，研究人员使用了一个强大的神经遗传模型系统：果蝇果蝇，它在实验室中表现出丰富的多感官行为，并且存在大量的分子遗传工具来研究和操纵已识别的神经元和神经回路。大量的证据表明，在苍蝇中，嗅觉信号增强了视觉稳定反射的强度，类似于我们自己的凝视稳定眼球运动。研究人员将测试这样的假设：嗅觉信号改变视觉处理途径中神经元的反应强度，以及嗅觉感觉途径通过释放生物胺的神经分泌细胞与视觉途径联系起来。研究人员利用虚拟现实飞行模拟器，以及使用最先进的多光子激发荧光显微镜的实时成像，在选定的中间神经元和支配大脑视觉区域的神经调节回路中遗传靶向钙报告基因。他们希望发现神经分泌细胞被气味兴奋，并释放生物胺到视觉处理中心，这反过来又改变了视觉运动回路的膜特性和突触整合。他们预计，基因沉默这些相互作用消除了对视觉运动的行为反应，众所周知，这是通过同时呈现气味线索来增强的。该项目在概念上与K-12学生的外展工作联系在一起，方法是配备一个移动的飞行实验室，在当地小学提供示范讲习班。