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

项目摘要/摘要 我们对大脑的不完全理解使我们很难理解 感觉缺陷和其他精神障碍的根源。嗅觉系统是一个建立起来的模型 理解感觉加工的基本机制，尽管它在嗅觉中的特殊作用(S) 加工和感知仍不清楚。在嗅球内，数千个嗅觉感受器神经元 表达相同受体蛋白的细胞聚集在称为肾小球的球神经束的一个或两个区域。 在那里，这些细胞突触到几十个二尖瓣和簇状细胞的顶端树突上，这些细胞只支配 那个小球，它的轴突为大脑高级区域提供了所有的输出。因此，灯泡的输入和 输出是解剖学定义的，它们在空间上重叠在肾小球中。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塑造。几十年来 对球状突触的研究导致了许多迹象表明，它复杂的突触网络可能参与了 产生嗅觉，如气味识别、辨别和适应。这个项目的目标是 就是定义嗅球在嗅觉中的作用，并了解 这是这些功能的基础。比较来自嗅觉感受器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在 并将指导对其突触网络的进一步研究。 我们开发了一种新的成像方法来确定这种输入-输出传递函数，方法是 用电压和钙比较单个肾小球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，肾小球的输出映射和信号 与输入映射相比，幅度对气味浓度变化的敏感度要低得多。这个结果 这表明嗅球有助于感知浓度不变性(即，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 嗅球在额外的嗅觉维度中的作用，并开始研究 这些转变背后的机制(S)。我们将成像肾小球的电压或钙反应 嗅觉感受器神经元的输入，以及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 输出地图。与此同时，我们将优化我们的产出与投入比较方法。我们期待着 我们的方法将适用于其他大脑区域。

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.