Dendritic signaling in the olfactory bulb

嗅球中的树突信号传导

基本信息

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
项目类别：
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&apos 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

项目摘要

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）：气味信息通过选择性激活嗅觉受体进行编码，并在地形上映射到嗅球中的肾小球。我们广泛的长期目标是了解球茎中的树突和突触信号传导机制，将这种映射的输入转化为输出神经元、二尖瓣细胞和簇状细胞中的气味编码尖峰模式。此申请是对 NOT-OD-09-058 的回应：“NIH 宣布恢复法案基金可用于竞争性修订申请”。我们将扩大家长奖励的具体目标范围。批准的目标是研究簇状细胞中的信号传导，重点关注同步、颗粒细胞突触连接和胆囊收缩素的神经调节。本次修订扩大了我们的研究范围，涵盖一氧化氮 (NO) 对嗅球二尖瓣细胞和颗粒细胞之间突触传递的神经调节。我们的新特定目标将测试这样的假设：嗅球中的 NO 信号传导会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，从而驱动二尖瓣细胞的 GABA 能抑制增加。新的目标与母公司拨款的目标相增强和协同。我们的实验方法包括电生理学和光学记录或刺激小鼠模型切片制剂中的神经元。公共健康相关性：这项工作将阐明嗅球中 NO 信号传导的神经生理学机制。尽管解剖学和行为学证据表明一氧化氮与嗅觉功能（包括气味记忆形成）有关，但这些机制尚未在细胞水平上进行研究。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。它对于理解神经退行性疾病（例如导致嗅觉障碍和记忆丧失的阿尔茨海默病）具有潜在的相关性。 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 将为莫内尔中心提供急需的支持，莫内尔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。莫内尔的发现涉及广泛的学科，为当地和国家经济增加价值。 Monell 目前拥有 150 名员工，近年来每年在地区经济活动中创造近 1600 万美元的收入。该中心的培训项目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莫内尔公司的两个职位，其中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。