Electrophysiology and imaging of Drosophila olfaction

描述（由申请人提供）：对整个动物王国嗅觉系统的分子生物学、结构和功能的研究揭示了进化遥远的动物物种（如昆虫和灵长类动物（包括人类））的许多共同设计特征（例如：大量的气味受体、精确的轴突收敛、活动的振荡同步）。有趣的是，许多这些设计特征在这些物种中以不同的方式实现（例如：不同的基因序列，突触类型和细胞形态）：比较这些不同的实现，并通过这种比较，确定它们共同的高级特征有助于我们识别嗅觉系统的功能规则。因为嗅觉回路与记忆结构紧密相关——人类对气味的记忆尤其生动且持久——理解嗅觉编码也有助于我们更好地理解联想记忆的本质及其潜在的生物学。目前的工作是为了了解这些嗅觉/记忆回路的基本生理学。这项工作将构成电生理学的基础，在此基础上，嗅觉学习的新细胞和系统研究可以在一个特别有利的模型系统中建立：实验将在果蝇的大脑中进行，利用数百个实验室在该系统上进行的一个世纪的遗传学和分子工作。由于果蝇基因的可获得性和我们现在对它们的了解，果蝇基因可以被控制，从而标记或操纵特定的神经元和电路。通过将这些强大的工具与电极记录和快速脑成像工具相结合，我们可以检查特定分子，神经元或突触在嗅觉功能中的作用。果蝇的大脑相对较小（约10万个神经元）也将大大简化破译更复杂系统（如人脑）中神经编码本质的任务，从而有助于更好地理解感知障碍的可能原因。

DESCRIPTION (provided by applicant): Studies of the molecular biology, structure and function of olfactory systems throughout the animal kingdom reveal many common design features (for example: large set of odorant receptors, precise axonal convergence, oscillatory synchronization of activity) across evolutionary distant animal species such as insects and primates (including humans). Interestingly, many of these design features are implemented differently (for example: different gene sequences, synaptic types and cell morphologies) across these many species: comparing these different implementations and, through this comparison, identifying their common high-level features helps us identify the rules of function of olfactory systems. Because olfactory circuits are tightly associated with memory structures-the memories of smells are particularly vivid and long lasting in humans-understanding olfactory coding also helps us better understand the nature of associative memories and their underlying biology. The present work is geared towards understanding the basic physiology of these olfactory/memory circuits. This work will constitute the electrophysiological foundation on which new cellular and systems studies of olfactory learning can be built in a particularly advantageous model system: experiments will be carried out with the brain of the fruit-fly Drosophifa, taking advantage of a century of genetics and molecular work by hundreds of laboratories on this system: by virtue of their accessibility and knowledge we now have of them, Drosophila genes can be controlled so as to either mark or manipulate specific neurons and circuits. By combining these powerful tools with electrode recordings and fast brain imaging tools, we can examine the role of specific molecules, neurons or synapses for olfactory function. The relatively small size of the Drosophila brain (~100,000 neurons) will also greatly simplify the task of deciphering the nature of neural codes in more complex systems, such as the human brain, thus contributing to a better understanding of the possible causes of perceptual disorders.