Neural Mechanisms of Cross-modal Integration in the Fruit Fly

这在科学上是令人望而生畏的，但社会向神经科学家提出了一个巨大的挑战，即如何从单个神经元的活动模式及其形成的微小相互连接的电路中发现复杂的大脑功能。一个重要的悬而未决的问题是，大脑如何整合不同的感觉输入，以创造对世界的凝聚力感知？神经学家很好地理解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--脑细胞电路如何将多个感官连接在一起--知之甚少。这个项目采用跨学科的方法，使用遗传学、活脑成像、虚拟现实行为和工程分析来确定基本的神经回路机制，通过这些机制将感觉形式整合为感知。研究人员试图确定将感觉模式联系在一起的细胞身份、细胞-细胞连接、功能和神经化学相互作用。在这项工作中，研究人员使用了一个强大的神经遗传学模型系统：果蝇，它在实验室中展示了丰富的多感官行为曲目，并且存在丰富的分子遗传学工具来研究和操纵已识别的神经元和神经回路。大量证据表明，在果蝇中，嗅觉信号增强视觉稳定反射的强度，类似于我们自己的稳定凝视的眼睛运动。研究人员将测试一种假设，即嗅觉信号改变视觉处理通路中神经元的反应强度，并且嗅觉通路通过神经分泌细胞释放生物胺而与视觉通路相连。研究人员利用虚拟现实飞行模拟器，并使用最先进的多光子激发荧光显微镜进行现场成像，在选定的中间神经元和支配大脑视觉区域的神经调制电路中进行遗传靶向钙报告。他们希望发现神经分泌细胞受到气味的刺激，并将生物胺释放到视觉处理中心，这反过来又改变了视觉运动回路的膜属性和突触整合。他们预计，通过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，这种行为反应会通过同时呈现气味线索来增强。该项目在概念上与一项面向K-12学生的外展工作联系在一起，方法是配备一个流动飞行实验室，在当地小学提供示范讲习班。

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.