Mechanisms of biophysical diversity within and between olfactory bulb mitral and tufted cells.

嗅球二尖瓣和簇状细胞内部和之间的生物物理多样性机制。

• 批准号: 9764324
• 负责人: Nathan G Glasgow
• 金额: $ 6.37万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764324
• 关键词: Action Potentials; Animal Behavior; Animals; Behavior; Biological Models; Biophysical Process; Biophysics; Brain; Brain region; Cells; Cellular Morphology; Collection; Complement; Computational Technique; Disease; Electrophysiology (science); Exhibits; Frequencies; Goals; Injections; Ion Channel; Knowledge; Linear Models; Link; Measures; Membrane; Methodology; Modeling; Morphology; Mus; Neurons; Neurosciences; Pattern; Pharmacology; Physiological; Population; Potassium Channel; Procedures; Property; Proteins; Regulation; Role; Sensory; Signaling Molecule; Slice; Statistical Models; Stimulus; System; Testing; Translating; Variant; base; biophysical model; cell type; complex biological systems; density; mitral cell; novel; olfactory bulb; predictive modeling; protein expression; relating to nervous system; response; sensory input; theories; voltage; voltage gated channel

Project Summary Complex biological systems are composed of diverse units, a feature which is exemplified throughout the brain. This diversity is evident at each scale from animal behavior, to distinct brain regions, to local circuit responses, to distinct cell types and their unique morphologies, to the diverse protein expression patterns and subcellular localization of those proteins. Reductionist theory suggests that understanding the diversity of the most basic building blocks will ultimately inform our understanding of differences in animal behavior. However, linking knowledge of diversity in protein expression to diverse behavior is challenging. Here we propose an experimental and computational approach to linking mechanisms of diversity between cells to how a given cell performs a computation - particularly to how that cell encodes specific features of a stimulus. We will use the mammalian olfactory bulb as a model system to probe how sensory information is encoded by its two main projection neuron types, mitral cells (MCs) and tufted cells (TCs). Our lab has previously demonstrated that cell-to-cell diversity of physiological properties within MCs increases the information transferred by a population of MCs, enhances its range of stimulus encoding, and limits its neural synchronization. However, the mechanisms that underlie the diversity within MCs are poorly understood. Whereas our lab and others have demonstrated diverse ion channel expression within MCs, the relationship between diverse ion channel expression and differential sensitivity to specific stimulus features has not been established. Importantly, understanding of this link is not established in any cell type across the brain. Yet, this link is essential to comprehend how the collection of ion channels in a cell create the emergent property of single neuron computation. Here we propose to test our central hypothesis that differences in functional ion channel expression within and between MCs and TCs govern the differential sensitivity to specific stimulus features across these cells. In Aim 1, we will determine the mechanisms of diversity within and between MCs and TCs. We will measure diversity across cells using a recently developed experimental and computational approach to creating biophysical models. We predict that levels of functional ion channel expression will covary across cells. In Aim 2, we will determine the role of the diversity of ion channel expression in stimulus encoding. We will use statistical approaches to determine how diverse functional ion channel expression relates to encoding of specific stimulus features and test novel hypotheses with recordings from MCs and TCs.

项目摘要 复杂的生物系统是由不同的单位组成的，这一特点在整个过程中得到了体现。 大脑这种多样性在从动物行为到不同大脑区域再到局部电路的各个层面上都很明显 反应，不同的细胞类型和它们独特的形态，不同的蛋白质表达模式， 这些蛋白质的亚细胞定位。还原论理论表明，理解的多样性， 最基本的构建模块将最终告知我们对动物行为差异的理解。然而，在这方面， 将蛋白质表达的多样性知识与不同的行为联系起来是具有挑战性的。在这里，我们提出一个 实验和计算的方法来连接细胞之间的多样性机制， 执行计算-特别是细胞如何编码刺激的特定特征。我们将使用 哺乳动物的嗅球作为模型系统，以探索感觉信息是如何编码的两个主要 投射神经元类型，二尖瓣细胞（MC）和簇状细胞（TC）。 我们的实验室先前已经证明，MCs内生理特性的细胞间多样性 增加了由MC群体传递的信息，增强了其刺激编码的范围， 限制了神经同步然而，在MC内的多样性的基础机制是差的 明白尽管我们的实验室和其他实验室已经证明了MC内不同的离子通道表达， 不同的离子通道表达和对特定刺激特征的不同敏感性之间的关系， 尚未建立。重要的是，对这种联系的理解并没有在大脑中的任何细胞类型中建立起来。 然而，这种联系对于理解细胞中离子通道的集合如何产生涌现是必不可少的。 单神经元计算的性质。 在这里，我们提出测试我们的中心假设，功能性离子通道表达的差异， 在MC和TC之内和之间，控制着对这些特定刺激特征的不同敏感性。 细胞在目标1中，我们将确定MC和TC内部和之间的多样性机制。我们将 使用最近开发的实验和计算方法测量细胞间的多样性， 创建生物物理模型。我们预测功能性离子通道的表达水平将在不同的时间点之间存在协变。 细胞在目标2中，我们将确定离子通道表达的多样性在刺激中的作用。 编码.我们将使用统计方法来确定不同功能离子通道表达 涉及特定刺激特征的编码和用来自MC和TC的记录测试新假设。