Mechanisms of olfactory signal processing

嗅觉信号处理机制

• 批准号: 8271454
• 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/8271454
• 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(申请人提供)：大多数气味是由许多不同分子的混合物组成的。我们的总体目标是利用啮齿动物嗅球切片的电生理和钙成像方法，以及电子显微镜方法，研究第一嗅觉处理结构--嗅球--提炼复杂气味信号的生理机制。我们的重点是在肾小球内工作的突触机制，这些结构既是鼻部嗅觉感受器神经元(ON)输入到球状细胞的位置，也是输出信号传递到嗅觉皮质的起点。这些输出信号由二尖瓣细胞(MC)携带。对这三个特定目标的研究将共同检验这样一个假设，即围绕每个肾小球的神经元的一个小微电路，包括兴奋性外部簇状(ET)细胞和抑制性小球周围(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质。这些对前两个目标中肾小球兴奋机制的研究将作为目标3中检验抑制性PG细胞如何与兴奋相互作用以抑制MC激活的实验的基础。通过ET-PG细胞微电路选择性地抑制微弱信号，可以增强相似气味之间的知觉差异，促进气味识别。我们研究气味识别的基本机制的实验，也可以作为理解与人类许多神经疾病相关的嗅觉缺陷的基础，如阿尔茨海默病、帕金森氏病和精神分裂症。所有这些疾病都会导致灯泡的结构变化，我们的研究表明灯泡电路的某些关键元件是如何参与电路水平的处理的，这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。 公共卫生相关性：在人类中，嗅觉功能障碍在许多神经疾病中都会遇到，如阿尔茨海默病、帕金森氏病和精神分裂症。我们对嗅球信息处理的基本机制的研究将为了解特定疾病相关的嗅觉缺陷以及潜在的治疗方法提供基础。