Dendritic signaling in the olfactory bulb

嗅球中的树突信号传导

• 批准号: 7808666
• 负责人: GRAEME LOWE
• 金额: $ 30万
• 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: 2009-09-09 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808666
• 关键词: Affect; Alzheimer' s Disease; Anxiety; Apical; Award; Basic Science; Behavioral; Brain; Brain Part; Calcium; Calcium Channel; Calcium Signaling; Cells; Chemicals; Cholecystokinin; Complex; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Data; Dendrites; Diabetes Mellitus; Discipline; Disease; Doctor of Philosophy; Drug Controls; Economics; Electrophysiology (science); Enzymes; Funding; Future; GABA Receptor; Glutamate Receptor; Image; Impairment; Inflammatory; Link; Malignant Neoplasms; Maps; Mediating; Membrane; Memory; Memory Loss; Methods; Modeling; Mus; Neuraxis; Neurodegenerative Disorders; Neurons; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Odors; Optics; Oranges; Output; Parents; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; Positioning Attribute; Postdoctoral Fellow; Preparation; Principal Investigator; Process; Records Controls; Recovery; Research; Role; Schizophrenia; Scientist; Sensory; Series; Signal Pathway; Signal Transduction; Signaling Molecule; Slice; Smell Perception; Solid; Soluble Guanylate Cyclase; Source; Stimulus; Synapses; Synaptic Transmission; Taste Perception; Testing; Thapsigargin; Training; Training Programs; Transgenic Mice; United States National Institutes of Health; Up-Regulation; Work; addiction; analog; base; density; depression; gamma-Aminobutyric Acid; granule cell; inhibitor/antagonist; insight; member; mouse model; neuronal cell body; neurophysiology; neuroregulation; neurotransmitter release; olfactory bulb; olfactory receptor; parent grant; postsynaptic; progesterone 11-hemisuccinate-(2-iodohistamine); programs; public health relevance; research study; response; voltage

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, mitral cells and tufted cells. This application is in response to NOT-OD-09-058: "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". We will expand the scope of the specific aims of the parent award. The approved aims investigate signaling in tufted cells, focusing on synchronization, granule cell synaptic connections and neuromodulation by cholecystokinin. This Revision expands our studies to cover neuromodulation of synaptic transmission between mitral and granule cells of the olfactory bulb by nitric oxide (NO). Our new Specific Aim will test the hypothesis that NO signaling in the olfactory bulb activates soluble guanylyl cyclase (sGC) in a subset of granule cells, leading to upregulation of granule cell calcium which drives increased GABAergic inhibition of mitral cells. The new aim augments and synergizes with aims of the parent grant. Our experimental approaches include electrophysiology and optical recording or stimulation of neurons in slice preparations in a mouse model. PUBLIC HEALTH RELEVANCE: This work will elucidate the neurophysiological mechanisms of NO signaling in the olfactory bulb. These mechanisms not been studied at the cellular level, in spite of anatomical and behavioral evidence implicating NO in olfactory function, including odor memory formation. Our research will offer new insights into regulation of neural activity underlying sensory function in the brain. It has potential relevance for understanding neurodegenerative disorders such as Alzheimers disease which cause olfactory impairment and memory loss. NO signaling is implicated in inflammatory diseases,cancer, diabetes.anxiety, addiction, depression and schizophrenia. This CRA will provided much needed support for the Monell Center, the nation's only non-profit basic research center devoted to chemical senses: taste, smell, and chemesthesis. Monell's discoveries extend across a broad range of disciplines and add value to the local and national economy. Monell currently employs 150 staff members and in recent years has generated close to $16M annually in regional economic activity. The Center's training programs produce highly-skilled research scientists for the future. The current proposal will help retain two positions at Monell, including a highly trained research associate scientist, thus directly contributing to economic stimulus and recovery.

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，长期的目标是了解树突和突触的信号传导机制，在灯泡转换这个映射输入到输出神经元，二尖瓣细胞和簇状细胞的气味编码尖峰模式。本申请是对NOT-OD-09-058的回应：“NIH宣布为竞争性修订申请提供恢复法案资金”。我们将扩大家长奖的具体目标范围。批准的目的是研究簇状细胞中的信号传导，重点是同步化，颗粒细胞突触连接和胆囊收缩素的神经调节。这一修订扩大了我们的研究，包括一氧化氮（NO）对嗅球的二尖瓣和颗粒细胞之间突触传递的神经调节。我们的新的特定目的将测试假设，即嗅球中的NO信号激活颗粒细胞亚群中的可溶性鸟苷酸环化酶（sGC），导致颗粒细胞钙的上调，从而增加对二尖瓣细胞的GABA能抑制。新的目标与父母补助金的目标相辅相成。我们的实验方法包括电生理学和光学记录或刺激的神经元切片制备在小鼠模型。 公共卫生相关性：这项工作将阐明嗅球中NO信号传导的神经生理机制。这些机制没有在细胞水平上进行研究，尽管解剖学和行为学证据暗示NO参与嗅觉功能，包括气味记忆的形成。我们的研究将为大脑感觉功能的神经活动调节提供新的见解。它对理解神经退行性疾病如阿尔茨海默病（Alzheimers disease）具有潜在的相关性，这些疾病会导致嗅觉障碍和记忆丧失。 NO信号传导与炎症性疾病、癌症、糖尿病、焦虑、成瘾、抑郁和精神分裂症有关。该CRA将为Monell中心提供急需的支持，Monell中心是美国唯一致力于化学感官（味觉，嗅觉和化学感觉）的非营利基础研究中心。Monell的发现涵盖了广泛的学科，并为当地和国家经济增加了价值。Monell目前拥有150名员工，近年来每年在区域经济活动中产生近1600万美元的收入。该中心的培训计划为未来培养高技能的研究科学家。目前的提议将有助于保留蒙内尔的两个职位，包括一名训练有素的研究助理科学家，从而直接促进经济刺激和复苏。