Glomeruli as Functional Units for Olfactory Coding

描述（由申请人提供）：包括人类在内的多种动物大脑中的初级嗅觉中心，其特征是一系列被称为肾小球的突触模块。这些中心以化学方式组织，因此气味信息在肾小球中以空间形式呈现。尽管化学感觉研究取得了巨大的进步，但我们仍然不明白气味刺激的信息是如何在肾小球内部和肾小球之间的神经活动中编码的，然后再传递到高阶皮层区域进行进一步处理。这个项目建立在一个坚实的技术经验和实验上有利的模型的知识基础上，Manduca sexta的嗅觉系统在组织和功能上与哺乳动物的嗅觉系统相当，并且允许对肾小球处理气味信息的假设进行神经生理学测试，比其他物种更精确。该模型系统具有解剖简单、可识别的肾小球、可接近的受体细胞和中枢神经元以及化学识别的、与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肾小球内部和之间的突触神经回路，以分析特定气味信息在大脑中的第一个中转站是如何处理的。通过细胞内记录和染色、细胞外多通道记录、激光扫描共聚焦显微镜以及关键突触受体的克隆、表达和药理研究，我们将重点关注已知气味“调谐”的“参考”肾小球及其邻近肾小球，以验证以下假设：(1)肾小球的投射（输出）神经元（PNs）具有功能多样性；(2) PNs的功能相似性与放电同步性增强相关；(3)肾小球内和肾小球间突触回路，尤其是抑制性连接，塑造了PNs的活动，包括放电的同步性，因此是理解中枢编码和气味信息整合的关键；(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理解，并有望有助于解释嗅觉障碍，如嗅觉缺失、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.