Glomeruli as Functional Units for Olfactory Coding

肾小球作为嗅觉编码的功能单位

• 批准号: 7262432
• 负责人: JOHN G HILDEBRAND
• 金额: $ 35.57万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7262432
• 关键词: Agonist; Animals; Anosmia; Area; Biological Models; Brain; Characteristics; Code; Complementary DNA; Complex; Condition; Detection; Distant; Dose; Drug usage; Exhibits; Fire - disasters; Foundations; GABA Agonists; GABA Receptor; Heterogeneity; Housing; Human; In Situ Hybridization; Individual; Insecta; Knowledge; Laser Scanning Confocal Microscopy; Lateral; Lobe; Manduca; Manduca sexta; Maps; Mediating; Modeling; Mushroom Bodies; Nature; Neurons; Neuropil; Northern Blotting; Odors; Oocytes; Output; Paraosmias; Pathway interactions; Pattern; Pharmacological Treatment; Phase; Pheromone; Physiological; Polymerase Chain Reaction; Process; Property; Receptor Cell; Research; Research Personnel; Reverse Transcription; Role; Sensory; Sensory Disorders; Shapes; Staining method; Stains; Standards of Weights and Measures; Stimulus; Synapses; Synaptic Receptors; System; Techniques; Testing; Tissues; Vertebrates; Xenopus laevis; base; experience; expression cloning; extracellular; gamma-Aminobutyric Acid; hyposmia; immunocytochemistry; male; neural circuit; neurophysiology; olfactory stimulus; postsynaptic; receptor; relating to nervous system; research study; response; synaptic inhibition; transmission process

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.

描述（由申请人提供）：包括人类在内的各种动物的大脑中的主要嗅觉中心的特征是一系列称为Glomeruli的突触模块。这些中心是在化合物上组织的，因此气味信息在肾小球中在空间上表示。尽管化学感应研究取得了巨大的进步，但我们仍然不了解有关气味刺激的信息如何在神经活动，肾小球内部和肾小球之间编码，然后再将到高阶皮质区域以进行进一步处理。该项目以实验性有利模型的牢固的技术经验和知识为基础，即Manduca Sexta的嗅觉系统，该系统可与其在组织和功能方面的哺乳动物对应物相媲美，并允许在其他物种中可以精确地进行异常信息的神经生理测试。该模型系统提供了解剖学简单，可识别的肾小球，可访问的受体细胞和中央神经元的优势，以及化学鉴定的，具有行为相关的气味。它还提供了一个非凡的机会，可以在已确定的肾小球内部和确定的肾小球内部的突触神经回路，以分析其在大脑中的第一个路线上如何处理特定的气味信息。通过细胞内记录和染色，细胞外多通道记录，激光扫描的共聚焦显微镜以及关键突触受体的克隆，表达和药物学研究，我们将重点介绍已识别的“参考”“参考”“参考”，以测试已知的odor及其邻近glomeruli的glomeruli and the neyuri and the neyuri shective the Proccessive the Proccessive offective（1）：（1）（1）（1（Fucfuct）：（1）（1（1）（1）（1（Fucfution）：（1）（1（Fucfution）：（1（Fucfution）：（1（Fucfution）：（1）（1）肾小球在功能上是多样的。 （2）PNS的功能相似性与增强的点火同步相关； （3）内部和胶体间突触电路，尤其是抑制性连接，塑造了PN的活性，包括射击同步，因此是理解气味信息的中央编码和整合的关键； （4）肾小球之间的突触相互作用在相邻的肾小球之间最强。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，并有望有助于解释感觉障碍，例如帕罗斯马病，低质量和厌食症。