Neuronal and Network Dynamics in the Olfactory System

描述(申请人提供)：当气味与鼻上皮中的气味感受器相互作用时，嗅觉开始。化学信号被转化为电脉冲信号，然后被发送到靠近嗅球表面的数千个肾小球。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神经元组成一个离散的功能模块，该模块介导与给定类型的气味感受器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存在技术困难，这一假设尚未得到直接验证。在这个方案中，我们使用了最近发展起来的转基因小鼠系，通过单肾小球电穿孔进行神经元标记和活体双光子光学成像技术。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定的解剖和功能构型。2)量化多个模块对单一气味和混合气味分子的时空活动模式。这些研究的结果将突出肾小球回路中信息处理的基本规律，并将有助于揭示嗅球中气味处理的机制。此外，他们将阐明在其他大脑区域进行信息处理的一般原理，并将促进未来旨在将网络动力学分析与单细胞特性相结合的研究。

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.