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，二尖瓣和簇状细胞中的气味编码尖峰模式。该申请是对NOT-OD-09-058的响应：“ NIH宣布为竞争性修订申请提供恢复法案的可用性”。我们将扩大父母奖的特定目标的范围。批准的目的研究了簇状细胞中的信号传导，重点是同步，颗粒细胞突触连接和胆囊基蛋白的神经调节。这项修订扩大了我们的研究，以涵盖通过一氧化氮（NO）的嗅球灯泡二尖瓣和颗粒细胞之间突触传播的神经调节。我们的新特定目的将检验以下假设：嗅球中没有信号传导在颗粒细胞的一个子集中激活可溶性鸟叶基环酶（SGC），从而导致颗粒细胞钙的上调，从而驱动了颗粒细胞的GABA能抑制。新目标增强并与父母赠款的目标协同作用。我们的实验方法包括电生理学和小鼠模型中切片制剂中神经元的光学记录或刺激。公共卫生相关性：这项工作将阐明嗅球中无信号传导的神经生理机制。尽管有解剖学和行为证据，涉及嗅觉功能，包括气味记忆的形成，但这些机制尚未在细胞水平上进行研究。我们的研究将为调节大脑的感觉功能的神经活动调节提供新的见解。它与理解神经退行性疾病（例如阿尔茨海默氏病）具有潜在相关性，这些疾病会导致嗅觉障碍和记忆力丧失。没有信号与炎症性疾病，癌症，糖尿病。焦虑，成瘾，抑郁和精神分裂症有关。该CRA将为Monell Center提供急需的支持，Monell中心是该国唯一致力于化学感官的非营利基础研究中心：口味，气味和化学感。 Monell的发现扩展了广泛的学科，并为地方和国民经济增加了价值。 Monell目前雇用150名员工，近年来，每年在区域经济活动中产生近1600万美元。该中心的培训计划为未来提供高技能的研究科学家。当前的提案将有助于保留Monell的两个职位，其中包括一位训练有素的研究助理科学家，因此直接有助于经济刺激和恢复。