Neural Ensemble Codes in Drosophila Olfaction

描述（由申请人提供）：开发了新的实验技术，通过光监测和操纵体内遗传限制的神经元群体。这些技术将用于研究果蝇（Drosophila melanogaster）嗅觉系统的信息处理。细胞类型特异性启动子和增强子将遗传编码的光学传感器和效应器靶向四个突触耦合处理层中的神经元：1）嗅觉受体神经元，其位于感觉表面并将轴突投射到触角叶（脊椎动物嗅球的类似物）; 2）触角叶的局部抑制性中间神经元; 3）将嗅觉信息从触角叶传递到蘑菇体的投射神经元，蘑菇体是脊椎动物嗅觉皮层的类似物; 4）肯扬细胞，蘑菇体的内在神经元。气味诱发的神经活动模式将通过光学显微镜在这些基因突出的处理阶段中的每一个进行可视化，并且将跟踪从处理阶段到处理阶段的活动传播。以这种创新策略为核心，将解决针对多层神经网络的基本操作原理的三个具体目标：1）用于表示四个嗅觉处理阶段中的每个阶段的气味信息的代码，以及与这些代码相关的映射规则，将被表征。2)在联合收割机结合光学成像和行为分析的实验中，我们将阐明表达抽象、分类和行为内涵的神经符号的计算起源、物理形式和语义内容。这些实验的重点将是用于连接享乐价的神经元基底（即，吸引力或厌恶性）的气味，并在其修改的经验。3)具有确定的神经或行为表型的突变，或将通过选择性光刺激插入遗传指定的靶神经元的人工神经信号，将用于干扰神经元生理学;将通过光学成像分析这些干扰在系统水平上的影响。这为我们提供了一个机会，让我们可以从细胞甚至分子的角度来理解集体网络的特性，从而超越目前将神经科学划分为分子、细胞和系统分支的一些界限。

DESCRIPTION (provided by applicant): Novel experimental technologies were developed to monitor and manipulate, through light, genetically circumscribed populations of neurons in vivo. These technologies will be harnessed to study information processing in the olfactory system of the fruit fly, Drosophila melanogaster. Cell-type specific promoters and enhancers will target genetically encoded optical sensors and effectors to neurons in four synaptically coupled processing layers: 1) To olfactory receptor neurons, which are located at the sensory surface and project axons to the antennal lobe, the analog of the vertebrate olfactory bulb; 2) to local inhibitory interneurons of the antennal lobe; 3) to projection neurons that relay olfactory information from the antennal lobe to the mushroom body, the analog of the vertebrate olfactory cortex; and 4) to Kenyon cells, the intrinsic neurons of the mushroom body. Odor-evoked neural activity patterns will be visualized by optical microscopy at each of these genetically highlighted processing stages, and the propagation of activity from processing stage to processing stage will be traced. With this innovative strategy at their core, three specific aims directed at the fundamental operational principles of a multi-layered neural network will be addressed: 1) The codes employed to represent odor information at each of the four olfactory processing stages, and the mapping rules that relate these codes, will be characterized. 2) The computational origin, physical form, and semantic content of neural symbols that express abstractions, classifications, and behavioral connotations will be elucidated in experiments that combine optical imaging with behavioral assays. The focus of these experiments will be on the neuronal substrate for attaching hedonic valence (i.e., attractiveness or repulsiveness) to odors, and on its modification by experience. 3) Mutations with defined neural or behavioral phenotypes, or artificial neural signals that will be inserted into genetically designated target neurons by selective photostimulation, will be used to perturb neuronal physiology; the impact of these perturbations at the systems level will be analyzed by optical imaging. This opens an opportunity to understand collective network properties in cellular or even molecular terms, and to transcend thereby some of the boundaries that currently divide neuroscience into molecular, cellular, and systems branches.