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(申请人提供)：气味信息通过选择性激活嗅觉感受器进行编码，并在地形图上映射到嗅球中的肾小球。我们广泛的长期目标是了解球状细胞中的树突和突触信号机制，这些机制将这种映射的输入转化为输出神经元-二尖瓣细胞和簇生细胞-的气味编码棘波模式。我们把重点放在簇状细胞上，这是嗅球中的一类主要神经元，但大多被忽视。簇生细胞与二尖瓣细胞在皮质投射、树突域、尖峰频率和分子接受范围的侧向抑制调谐方面不同。我们的工作假设是，嗅球的感觉处理被包含簇状细胞和二尖瓣细胞的子回路分成几个平行的通路。我们将通过分析和对比丛生细胞相对于二尖瓣细胞的棘波计时和同步，通过绘制连接到丛生细胞和二尖瓣细胞的局部神经元间回路的空间结构，以及通过确定棘波同步的生物物理和突触机制来验证这一理论。我们还将分析丛生细胞到颗粒细胞的球内投射，将镜像对称的肾小球映射联系起来，并测试神经肽CCK在这些投射中作为辅助递质或调节器的作用的特定模型。我们的工作将对差异编码和动态抑制机制产生新的见解，这些机制调节感觉系统中的节律性尖峰活动。我们的实验方法包括结合膜片钳电生理学和光记录或刺激在啮齿动物模型的切片制备中。公共卫生相关性这项工作解决了我们在处理感觉信息的嗅球电路的连接性和突触生理学知识方面的一个主要缺口。这对于理解大脑回路的同步性和动力学具有广泛的意义，对于提高我们对癫痫和痴呆等神经元网络协调的病理机制的理解也有重要意义。我们还采取了开创性的步骤，开发了一种新的细胞模型，用于分析参与肿瘤发生的多肽信号转导途径。