DENDRITIC SIGNALING IN THE OLFACTORY BULB

嗅球中的树突信号传导

• 批准号: 7849879
• 负责人: GRAEME LOWE
• 金额: $ 16.11万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849879
• 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）：气味信息通过嗅觉受体的选择性激活进行编码，并以拓扑学方式映射到嗅球中的肾小球。我们广泛的长期目标是了解灯泡中的树突和突触信号传导机制，这些机制将映射的输入转换为输出神经元（二尖瓣细胞和簇状细胞）中的气味编码尖峰模式。我们专注于簇状细胞，在嗅球的主要神经元，已被大多数人忽视的主要类别。簇状细胞与二尖瓣细胞在皮质投射、树突区、尖峰频率和分子感受范围的侧抑制调谐方面不同。我们的工作假设是嗅球中的感觉处理被包含簇状细胞和僧帽细胞的子回路分成平行的通路。我们将通过分析和对比簇状细胞相对于二尖瓣细胞的尖峰定时和同步，绘制出连接到簇状细胞和二尖瓣细胞的局部中间神经元电路的空间结构，以及确定尖峰同步的生物物理和突触机制来测试这一理论。我们还将分析球内预测的簇状细胞颗粒细胞连接镜像对称的肾小球地图，并测试一个特定的模型的神经肽胆囊收缩素作为一个共同的发射器或调制器在这些预测的作用。我们的工作将产生新的见解差异编码和动态抑制机制调节节奏的尖峰活动的感觉系统。我们的实验方法包括膜片钳电生理学和光学记录或刺激切片制备在啮齿动物模型的组合。公共卫生相关性这项工作解决了我们对处理感觉信息的嗅球回路的连接性和突触生理学知识的一个主要空白。它对于理解脑回路的同步和动力学具有广泛的意义，并且与提高我们对神经元网络协调中的病理学的理解有关，例如癫痫和痴呆。我们还采取开拓性的步骤，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。