Neuronal and Network Dynamics in the Olfactory System

描述（由申请人提供）：嗅觉感觉开始于气味剂与鼻上皮中的气味受体相互作用。化学信号被转换成电脉冲信号，然后被送到嗅球表面附近的数千个肾小球。重要的是，与相同气味受体相关的气味信号汇聚到几个肾小球，每个肾小球代表一个单一的气味受体。因此，长期以来，人们一直认为单个肾小球和所有相关的神经元组成了一个离散的功能模块，它介导了与特定类型的气味受体相关的气味信息的处理。然而，由于同时可视化和检测模块内每个神经元的活动的技术困难，这一假设尚未得到直接测试。在这个提议中，我们采用了最近开发的转基因小鼠系，通过单肾小球电穿孔和体内双光子光学成像技术进行神经元标记。我们的目标是揭示肾小球模块的结构和功能组织，并确定相邻模块之间的相互作用，重点关注以下具体目标；1)确定单个肾小球模块的细胞类型特异性解剖和功能配置。2)量化多个模块对单一气味分子和混合气味分子的时空活动模式。从这些研究中获得的结果将强调肾小球回路中信息处理的基本规则，并将有助于揭示嗅球中气味处理的机制。此外，它们将揭示其他大脑区域信息处理的一般原理，并将促进旨在将网络动力学分析与单细胞特性结合起来的未来研究。

DESCRIPTION (provided by applicant): Olfactory sensation begins when odorants interact with odorant receptors in the nasal epithelium. The chemical signal is transformed into an electric spike signal, before being sent to the thousands of glomeruli near the surface of the olfactory bulb. Importantly, odor signals associated with the same odorant receptors converge to a few glomeruli and each glomerulus represents a single odorant receptor. Therefore, it has long been assumed that a single glomerulus and all associated neurons compose a discrete functional module, which mediates the processing of odor information associated with a given type of odorant receptor. However this hypothesis has not been directly tested, owing to the technical difficulties of simultaneously visualizing and detecting the activity of each neuron within a module. In this proposal, we employ recently developed transgenic mouse lines, neuronal labeling by single glomerular electroporation and in vivo two-photon optical imaging techniques. Our goals are to reveal the structural and functional organization of the glomerular module and to determine the interaction between adjacent modules, focusing on the following specific aims; 1) Determine the cell-type specific anatomical and functional configuration of a single glomerular module. 2) Quantify the spatiotemporal activity patterns of multiple modules in response to single odorants and mixtures of odorant molecules. The results gained from these studies will highlight the fundamental rules that underlie information processing in glomerular circuits and will help to reveal the mechanisms of odor processing in the olfactory bulb. Moreover, they will shed light on general principles that underlie information processing in other brain regions and will facilitate future studies that aim to combine the analysis of network dynamics with single cell properties.