Defining the functions of olfactory bulb processing via comparison of input and output

通过输入和输出的比较定义嗅球处理的功能

• 批准号: 9461038
• 负责人: Douglas Anthony Storace
• 金额: $ 5.19万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2018-12-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9461038
• 关键词: Aging-Related Process; Alzheimer' s Disease; Anatomy; Animals; Apical; Attenuated; Axon; Brain; Brain region; Calcium; Cells; Complex; Data; Dendrites; Dependence; Dimensions; Discrimination; Exhibits; Feedback; Goals; Image; Individual; Interneurons; Lateral; Maps; Mediating; Mental disorders; Modeling; Neurons; Neuropil; Olfactory Pathways; Olfactory Receptor Neurons; Output; Parkinson Disease; Pathway interactions; Perception; Peripheral; Population; Process; Role; Sensory; Signal Transduction; Smell Perception; Stimulus; Stream; Suggestion; Synapses; Time; cell type; experimental study; human disease; imaging approach; individual response; mitral cell; neural circuit; novel; novel strategies; olfactory bulb; olfactory stimulus; receptor; response; sensor; sensory mechanism; voltage

Project Summary/Abstract Our incomplete understanding of the brain makes it challenging to understand the mechanisms that underlie sensory deficits and other psychiatric disorders. The olfactory system is an established model for understanding the basic mechanisms of sensory processing, although its specific role(s) in olfactory processing and perception remain unclear. In the olfactory bulb, thousands of olfactory receptor neurons each expressing the same receptor protein converge onto one or two regions of bulb neuropil called glomeruli. There these cells synapse onto the apical dendrites of a few dozen mitral and tufted cells which only innervate that glomerulus, and whose axons provide all of the output to higher brain regions. Thus, the bulb’s input and output are defined anatomically and they spatially overlap in glomeruli. This input-output transformation is shaped by more than 20 different interneuron cell types and feedback from several brain regions. Decades of studying the bulb has led to a number of suggestions that its complex synaptic network may be involved in generating olfactory perceptions like odorant recognition, discrimination and adaptation. The goal of this project is to define the role of the olfactory bulb in olfactory perception, and to understand the mechanisms that underlie those functions. Comparing the signals from the olfactory receptor neuron input and the mitral and tufted cell output can provide definitive statements about the information transformations that occur in the olfactory bulb, and will guide further studies of its synaptic network. We have developed a novel imaging approach to determine this input-output transfer function by comparing the activity signals of both the input and the output of individual glomeruli using voltage and calcium sensors. Our preliminary data using this approach revealed that the glomerular output maps and signal amplitude were much less sensitive to changes in odorant concentration than the input maps. This result suggests that the olfactory bulb contributes to the perception of concentration invariance (i.e., that an odorant is considered the same over a range of concentrations). Here we propose to use our approach to examine the role of the olfactory bulb in an additional olfactory perceptual dimension, and to begin to investigate the mechanism(s) behind these transformations. We will image the voltage or calcium response of the glomerular olfactory receptor neuron input, and the glomerular or individual mitral and tufted cell output in each of these aims. These experiments will generate the first mapping of the glomerular input maps onto the glomerular output maps. At the same time we will optimize our approach for comparing output with input. We expect that our approach will have application to other brain regions.

项目总结/摘要 我们对大脑的不完全理解使得理解大脑的机制变得具有挑战性， 是感官缺陷和其他精神疾病的基础。嗅觉系统是一个既定的模型， 理解感觉处理的基本机制，尽管它在嗅觉中的具体作用 处理和感知仍然不清楚。在嗅球中，数千个嗅觉受体神经元， 表达相同受体蛋白的细胞聚集在称为肾小球的球状神经元的一个或两个区域。 在那里，这些细胞与几十个二尖瓣和簇状细胞的顶树突形成突触， 肾小球，其轴突提供所有的输出到更高的大脑区域。因此，灯泡的输入和 输出在解剖学上被定义，并且它们在肾小球中空间上重叠。这种输入输出转换是 由20多种不同的中间神经元细胞类型和来自几个大脑区域的反馈形成。几十年的 对灯泡的研究提出了许多建议，认为其复杂的突触网络可能与 产生嗅觉感知，如气味识别、辨别和适应。这个项目的目标 是定义嗅球在嗅觉感知中的作用，并了解 这些功能的基础。比较来自嗅觉受体神经元输入和二尖瓣的信号， 簇状单元格输出可以提供有关 嗅球，并将指导其突触网络的进一步研究。 我们已经开发了一种新的成像方法来确定这种输入输出传递函数， 使用电压和钙比较单个肾小球的输入和输出的活动信号 传感器.我们使用这种方法的初步数据显示，肾小球输出图和信号 振幅对气味剂浓度变化的敏感性比输入图低得多。这一结果 表明嗅球有助于浓度不变性的感知（即，一种气味 在一定浓度范围内被认为是相同的）。在这里，我们建议使用我们的方法来检查 嗅球的作用，在一个额外的嗅觉知觉方面，并开始调查， 这些转变背后的机制。我们将对肾小球的电压或钙反应进行成像， 嗅觉受体神经元的输入，以及这些神经元中的肾小球或单个二尖瓣和簇状细胞的输出。 目标。这些实验将生成肾小球输入映射到肾小球的第一个映射。 输出映射。与此同时，我们将优化我们的方法来比较输出与输入。我们预计 我们的方法将应用于其他大脑区域。