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

项目摘要 复杂的生物系统由不同的单元组成，这一特征贯穿始终 大脑。这种多样性在每个尺度上都很明显，从动物行为，到不同的大脑区域，再到局部环路 对不同的细胞类型及其独特的形态，对不同的蛋白质表达模式和 这些蛋白质的亚细胞定位。简化论者的理论认为，理解生物多样性 最基本的构件最终将帮助我们理解动物行为的不同。然而， 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，我们提出一种 用实验和计算方法将细胞间的多样性机制与一个给定的细胞 进行计算--特别是计算该细胞如何编码刺激的特定特征。我们将使用 哺乳动物嗅球作为一个模型系统来探索感觉信息是如何通过它的两个主要的 投射神经元类型、二尖瓣细胞(MC)和簇状细胞(TCS)。 我们的实验室之前已经证明了MC内细胞间生理特性的多样性 增加MC群体传递的信息，增强其刺激编码范围，以及 限制了它的神经同步。然而，构成跨国公司内部多样性的机制并不完善。 明白了。鉴于我们的实验室和其他实验室已经展示了MC内不同的离子通道表达， 不同的离子通道表达与对特定刺激特征的差异敏感性之间的关系 没有得到证实。重要的是，对这种联系的理解并不是在大脑中的任何细胞类型中建立的。 然而，这种联系对于理解细胞中的离子通道集合如何创建紧急情况是必不可少的 单神经元计算的性质。 在这里，我们建议检验我们的中心假设，即功能离子通道表达的差异 MC和TC内部和之间控制着对这些特定刺激功能的差异敏感性 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。我们会 使用最近开发的实验和计算方法来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 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的离子通道表达 涉及对特定刺激特征的编码，并使用MC和TCS的录音来测试新的假设。

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.