Neural Ensemble Codes in Drosophila Olfaction

描述（由申请人提供）：开发了新的实验技术，通过光来监测和操纵体内遗传受限的神经元群体。这些技术将被用于研究果蝇嗅觉系统的信息处理。细胞类型特异性启动子和增强子将基因编码的光学传感器和效应器靶向于四个突触耦合处理层的神经元：1)嗅觉受体神经元，位于感觉表面并将轴突投射到触角叶，类似于脊椎动物的嗅球；2)触角叶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，类似于脊椎动物的嗅觉皮层；4)凯尼恩细胞，蘑菇体的固有神经元。气味诱发的神经活动模式将在每个基因突出的加工阶段通过光学显微镜可视化，并且活动从加工阶段到加工阶段的传播将被追踪。以这一创新策略为核心，将解决针对多层神经网络基本操作原理的三个具体目标：1)在四个嗅觉处理阶段中用于表示气味信息的代码，以及与这些代码相关的映射规则，将被表征。2)通过结合光学成像和行为分析的实验，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。这些实验的重点将放在将快乐价（即吸引力或厌恶性）附加到气味的神经元基质上，以及通过经验对其进行修改。3)具有特定神经或行为表型的突变，或通过选择性光刺激将人工神经信号插入基因指定的目标神经元，将用于扰乱神经元生理；这些扰动对系统水平的影响将通过光学成像进行分析。这为从细胞甚至分子的角度理解集体网络特性提供了机会，从而超越了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.