DENDRITIC SIGNALING IN THE OLFACTORY BULB

嗅球中的树突信号传导

• 批准号: 7689736
• 负责人: GRAEME LOWE
• 金额: $ 29.41万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689736
• 关键词: Address; Autoreceptors; Axon; Binding; Biological Models; Brain; Calcium; Cell Count; Cell model; Cells; Cholecystokinin; Cholecystokinin B Receptor; Code; Coupling; Data; Dementia; Dendrites; Electrophysiology (science); Employee Strikes; Epilepsy; Exhibits; Feedback; Figs - dietary; Frequencies; Glutamates; Image; Individual; Interneurons; Knowledge; Label; Lasers; Lateral; Link; Maps; Medial; Modeling; Molecular; N-Methylaspartate; Neurons; Neuropeptides; Odors; Olfactory Cortex; Optics; Output; Pathology; Pathway interactions; Pattern; Peptides; Physiological; Physiology; Preparation; Process; Receptor Activation; Relative (related person); Rodent; Rodent Model; Role; Scanning; Sensory; Sensory Process; Signal Transduction; Signal Transduction Pathway; Slice; Stimulus; Stream; Structure; Synapses; System; Systems Analysis; Testing; Time; Work; base; computerized data processing; granule cell; improved; insight; neural circuit; neuronal cell body; olfactory bulb; olfactory receptor; patch clamp; progesterone 11-hemisuccinate-(2-iodohistamine); public health relevance; research study; response; role model; sensory system; theories; transmission process; tumorigenesis

DESCRIPTION (provided by applicant): Odor information is encoded by selective activation of olfactory receptors and mapped topographically to glomeruli in the olfactory bulb. Our broad, long term objective is to understand dendritic and synaptic signaling mechanisms in the bulb that transform this mapped input into odor-encoding spike patterns in output neurons - the mitral cells and tufted cells. We focus on the tufted cells, a major class of principal neurons in the olfactory bulb that has been mostly ignored. Tufted cells differ from mitral cells in their cortical projections, dendritic fields, spike frequencies, and lateral inhibitory tuning of molecular receptive ranges. Our working hypothesis is that sensory processing in the olfactory bulb is split into parallel pathways by sub-circuits containing the tufted cells and mitral cells. We will test this theory by analyzing and contrasting the spike timing and synchronization of tufted cells relative to mitral cells, by mapping out the spatial structure of local interneuron circuits that link to tufted cells and mitral cells, and by determining biophysical and synaptic mechanisms of spike synchrony. We will also analyze the intrabulbar projections of tufted cells to granule cells linking mirror symmetric glomerular maps, and test a specific model for the role of the neuropeptide cholecytokinin as a co-transmitter or modulator in these projections. Our work will yield new insights into differential coding and dynamic inhibitory mechanisms regulating rhythmic spike activity in a sensory system. Our experimental approaches include a combination of patch-clamp electrophysiology and optical recording or stimulation in slice preparations in a rodent model. PUBLIC HEALTH RELEVANCE This work address a major gap in our knowledge of connectivity and synaptic physiology of circuits in the olfactory bulb that process sensory information. It has broad significance for understanding the synchronization and dynamics of brain circuits,.and is relevant to improving our understanding of pathologies in the coordination of neuronal networks, such as epilepsy and dementia. We also take pioneering steps in developing a new cellular model for analyzing a peptide signal transduction pathway that is involved in oncogenesis.

描述（由申请人提供）：气味信息是通过选择性激活嗅觉受体并在地形上映射到嗅球中肾小球的。我们广泛的长期目标是了解灯泡中的树突状和突触信号传导机制，这些机制将映射的输入转化为输出神经元中的气味编码尖峰模式 - 二尖瓣细胞和簇状细胞。我们专注于簇状细胞，簇状细胞是嗅球中主要的主要主神经元类，主要被忽略。簇状细胞与二尖瓣细胞的皮质投影，树突状场，尖峰频率和分子接受范围的侧面抑制性调节不同。我们的工作假设是，通过含有簇的细胞和二尖瓣细胞的亚电路将嗅球中的感觉处理分为平行途径。我们将通过分析和对比簇簇细胞相对于二尖细胞的尖峰时序和同步来测试该理论，并通过绘制与簇状细胞和二尖瓣连接的局部核元电路的空间结构，并确定尖峰同步的生物物理和突触机制。我们还将分析簇状细胞的簇内投影到连接镜子对称肾小球图的颗粒细胞，并测试一个特定模型，以作为神经肽胆固醇胆碱蛋白作为共肽或调节剂在这些投影中的作用。我们的工作将为调节感觉系统中节奏的尖峰活性的差异编码和动态抑制机制提供新的见解。我们的实验方法包括在啮齿动物模型中的切片制剂中的贴片钳电生理学和光学记录或刺激的结合。公共卫生相关性这项工作解决了我们对处理感官信息的嗅球中电路连通性和突触生理学的了解的主要差距。它对于理解脑电路的同步和动力学具有广泛的意义，并且与我们改善我们对神经元网络协调（例如癫痫和痴呆症）中病理的理解有关。我们还采取了开拓步骤，以开发一种新的细胞模型，用于分析参与肿瘤发生的肽信号转导途径。