Neural Ensemble Codes in Drosophila Olfaction

描述(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黑腹果蝇嗅觉系统的信息处理。细胞型特异性启动子和增强子将针对四个突触耦合处理层中的神经元以遗传编码的光学传感器和效应器为靶点：1)嗅觉感受器神经元，位于感觉表面并将轴突投射到触角叶，类似脊椎动物的嗅球；2)触角叶的局部抑制中间神经元；3)投射神经元，将嗅觉信息从触角叶传递到蘑菇体，脊椎动物嗅觉皮质的类似物；以及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每个基因突出的处理阶段可视化，并将跟踪活动从一个处理阶段到另一个处理阶段的传播。以这一创新策略为核心，将针对多层神经网络的基本工作原理解决三个具体目标：1)将表征在四个嗅觉处理阶段中的每一个阶段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。2)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将在光学成像和行为分析相结合的实验中阐明。这些实验的重点将放在将享乐性价态(即吸引力或排斥性)附加到气味上的神经元底物，以及经验对其进行修改。3)具有特定神经或行为表型的突变，或将通过选择性光刺激插入到遗传指定的目标神经元中的人工神经信号，将被用来扰乱神经生理学；这些扰动在系统水平上的影响将通过光学成像进行分析。这为理解细胞甚至分子方面的集体网络属性提供了机会，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.