Glomeruli as Functional Units for Olfactory Coding

描述(申请人提供)：包括人类在内的不同动物大脑中的主要嗅觉中心由一系列称为肾小球的突触模块来表征。这些中心是按化学方法组织起来的，因此气味信息在肾小球中呈现在空间上。尽管化学感觉研究取得了巨大的进步，但我们仍然不清楚有关气味刺激的信息是如何在神经活动中编码的，在被传递到更高级别的皮质区域进行进一步处理之前，在肾小球内和肾小球之间。这个项目建立在坚实的技术经验和关于实验上有利的模型的知识的基础上，Manduca sexta的嗅觉系统在组织和功能上与其哺乳动物相当，并允许对关于肾小球处理气味信息的假说进行神经生理学测试，比在其他物种中可能的更精确。该模型系统具有解剖结构简单、肾小球可识别、受体细胞和中枢神经元容易接近以及化学可识别的、行为相关的气味等优点。它还提供了一个难得的机会来解开已识别的肾小球内和肾小球之间的突触神经电路，以便分析特定的气味信息是如何在大脑中的第一个中转站处理的。通过细胞内记录和染色、细胞外多道记录、激光扫描共聚焦显微镜以及关键突触受体的克隆、表达和药理学研究，我们将重点关注已识别的气味“调谐”的“参考”肾小球及其邻近的肾小球，以检验以下假设：(1)肾小球的投射(输出)神经元(PN)功能多样；(2)PNS的功能相似与增强的放电同步性相关；(3)肾小球内和肾小球间的突触电路，特别是抑制性连接，塑造了PNS的活动，包括放电的同步性，因此是理解气味信息的中枢编码和整合的关键；(4)相邻肾小球之间的突触相互作用最强。这项研究将促进对包括人类在内的所有动物的基本嗅觉机制的了解，并有望有助于解释感觉障碍，如嗅觉异常、嗅觉减退和嗅觉缺失。

DESCRIPTION (provided by applicant): The primary olfactory centers in the brains of diverse animals, including humans, are characterized by an array of synaptic modules called glomeruli. These centers are organized chemotopically, such that odor information is represented spatially among glomeruli. Despite dramatic advances in chemosensory research, we still do not understand how information about odor stimuli is encoded in neural activity, within and among glomeruli, before being relayed to higher-order cortical areas for further processing. This project builds on a firm foundation of technical experience and knowledge about an experimentally favorable model, the olfactory system of Manduca sexta, which is comparable to its mammalian counterpart in organization and function and permits neurophysiological testing of hypotheses about glomerular processing of odor information with greater precision than has been possible in other species. This model system offers the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and central neurons, and chemically identified, behaviorally relevant odors. It also offers an exceptional opportunity to unravel synaptic neural circuitry within and among identified glomeruli in order to analyze how specific odor information is processed at its first way-station in the brain. By means of intracellular recording and staining, extracellular multichannel recording, laser-scanning confocal microscopy, and cloning, expression and pharmcological studies of key synaptic receptors, we will focus on identified "reference" glomeruli of known odor "tuning" and their neighboring glomeruli to test the hypotheses that: (1) the projection (output) neurons (PNs) of a glomerulus are functionally diverse; (2) functional similarity of PNs correlates with enhanced firing synchrony; (3) intra- and interglomerular synaptic circuitry, and especially inhibitory connections, shape the activity of PNs, including synchrony of firing, and thus is key to understanding central coding and integration of odor information; and (4) synaptic interactions between glomeruli are strongest between adjacent glomeruli. This research will promote understanding of basic olfactory mechanisms in all animals, including mankind, and promises to contribute toward explanation of sensory disorders such as parosmia, hyposmia, and anosmia.