Mechanisms of olfactory signal processing

嗅觉信号处理机制

• 批准号: 8079517
• 负责人: NATHAN Eric SCHOPPA
• 金额: $ 30.71万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079517
• 关键词: Action Potentials; Alzheimer' s Disease; Calcium; Cells; Collaborations; Complex; Data; Dendrites; Discrimination; Disease; Dyes; Electrons; Elements; Environment; Foundations; Functional disorder; Fura-2; Glutamates; Human; Image; Lateral; Lead; Link; Maps; Measurable; Measurement; Mediating; Methods; Microscopic; Neurons; Nose; Odorant Receptors; Odors; Olfactory Cortex; Olfactory Receptor Neurons; Output; Parkinson Disease; Pattern; Physiological; Population; Process; Property; Resistance; Rodent; Role; Schizophrenia; Signal Transduction; Site; Slice; Smell Perception; Structure; Synapses; Testing; Universities; Work; base; computerized data processing; granule cell; imaging modality; information processing; nervous system disorder; neuronal cell body; novel; olfactory bulb; patch clamp; public health relevance; research study; transmission process

DESCRIPTION (provided by applicant): Most odors are composed of a mixture of many different molecules. Our overall objective is to study the physiological mechanisms by which the first olfactory processing structure, the olfactory bulb, refines complex odor signals, using electrophysiological and calcium imaging methods in rodent olfactory bulb slices, along with electron microscopic methods. Our focus is on synaptic mechanisms that operate within glomeruli, which are structures that act as both the site of input into the bulb from olfactory receptor neurons (ORNs) in the nose and also the starting point for output signals that pass onto the olfactory cortex. These output signals are carried by mitral cells (MCs). Studies in the three Specific Aims together will test the hypothesis that a small microcircuit of neurons that surround each glomerulus, involving excitatory external tufted (ET) cells and inhibitory periglomerular (PG) cells, dictates whether any particular odor signal passes onto the cortex in the form of MC action potentials. These studies of excitatory mechanisms in the glomerulus in the first two Aims will serve as the basis for experiments in Aim 3 that examine how inhibitory PG cells interact with excitation to suppress MC activation. Selective suppression of weak signals by the ET-PG cell microcircuit could enhance perceptual differences between similar odors and facilitate odor discrimination. Our experiments, studying basic mechanisms of odor discrimination, could also serve as the basis for understanding olfactory deficits associated with many neurological disorders in humans, such as Alzheimer's disease, Parkinson's disease, and schizophrenia. All of these diseases are known to cause structural changes in the bulb, and our studies showing how certain key elements of the bulb circuit are involved in circuit level processing, will provide the foundation for linking disease-associated structural changes to olfactory dysfunction. PUBLIC HEALTH RELEVANCE: In humans, dysfunctions in the sense of smell are encountered in many neurological disorders such as Alzheimer's disease, Parkinson's disease, and schizophrenia. Our studies of the basic mechanisms of information processing in the olfactory bulb will provide the basis for understanding specific disease- associated olfactory deficits and also potential treatments.

描述（由申请人提供）：大多数气味由许多不同分子的混合物组成。我们的总体目标是研究的生理机制，第一个嗅觉加工结构，嗅球，细化复杂的气味信号，使用电生理和钙成像方法在啮齿动物嗅球切片，沿着与电子显微镜的方法。我们的重点是在肾小球内运作的突触机制，肾小球是既作为从鼻子中的嗅觉受体神经元（ORN）输入到球的位点，也作为传递到嗅觉皮层的输出信号的起点的结构。这些输出信号由二尖瓣细胞（MC）携带。 三个特定目标的研究将一起测试假设，即围绕每个肾小球的神经元的小微电路，包括兴奋性外部簇状（ET）细胞和抑制性肾小球周围（PG）细胞，决定是否有任何特定的气味信号以MC动作电位的形式传递到皮层。前两个目标中肾小球兴奋机制的这些研究将作为目标3中实验的基础，该实验研究抑制性PG细胞如何与兴奋相互作用以抑制MC激活。通过ET-PG细胞微电路选择性抑制弱信号可以增强相似气味之间的感知差异，并促进气味辨别。 我们的实验，研究气味辨别的基本机制，也可以作为理解与人类许多神经系统疾病相关的嗅觉缺陷的基础，如阿尔茨海默病，帕金森病和精神分裂症。所有这些疾病都已知会导致灯泡的结构变化，我们的研究表明灯泡回路的某些关键元素如何参与回路水平的处理，将为将疾病相关的结构变化与嗅觉功能障碍联系起来提供基础。 公共卫生关系：在人类中，嗅觉功能障碍在许多神经系统疾病中遇到，如阿尔茨海默病，帕金森病和精神分裂症。我们对嗅球信息处理的基本机制的研究将为理解特定疾病相关的嗅觉缺陷和潜在的治疗方法提供基础。