An Origin of Temporal Coding in the Early Olfactory System

 描述(申请人提供)：神经科学领域的一个基本目标是学习大脑如何处理感觉信息。了解神经元在正常情况下如何表示感觉刺激，可以在病理情况下识别受损成分，并制定具体的、有针对性的策略来治疗它们。啮齿动物嗅觉系统在探测感觉编码方案方面表现出许多独特的优势，包括它在解剖学上是紧凑的，并且完全服从于所有当前的遗传工具。自从发现嗅觉受体基因家族定义了许多离散的信息通道以来，这个领域已经取得了很大的进展，这些信息通过球提供给嗅球。尽管如此，对于嗅觉系统中的神经编码如何构建气味特征的表征，仍然没有连贯的理论。这项建议通过提出一个模型来解决这个问题，该模型将嗅球输入和输出水平上的表示联系起来，并通过实验测试其预测。具体地说，该项目试图解释在二尖瓣和簇状细胞(MTC)群体的反应中观察到的时间结构的来源，每个MTC接受来自单个肾小球的输入，并形成球茎的输出。我们的核心假设是，气味激活肾小球的顺序直接影响连接的MTCs的反应的符号和时间。目的1验证该模型的基本预测：在被气味激活的时空序列中，较早的肾小球将主要在连接的MTC中激发早期的兴奋性反应，而从较晚的肾小球接受输入的细胞将表现出一组不同的反应。目标2将确定这种编码方案是否像模型中的潜在机制预测的那样，在一定的浓度范围内有效。目的3因果关系地探讨群体内肾小球的早期激活是否会降低其MTCs反应的异质性。建议的编码方案有可能以一种可以容忍浓度变化的方式来传达关于气味的身份的信息。这些想法将利用光遗传学和电生理学的最新技术进步进行测试，这些技术允许研究人员定位并记录功能上与特定肾小球通道相连的MTCs的气味活动。拟议的实验将构成主要研究人员毕业论文工作的基础，并将在未来3年内进行。赞助商将在整个过程中提供指导，特别是在计算方面和分析方面。这项工作将在科学会议上公布，并将在完成后发表并向公众提供。

 DESCRIPTION (provided by applicant): A fundamental goal in the field of neuroscience is to learn how the brain processes sensory information. Understanding how neurons represent sensory stimuli under normal conditions provides the ability to identify compromised components in situations of pathology and develop specific, targeted strategies to treat them. The rodent olfactory system presents many unique advantages to probe sensory coding schemes, including that it is anatomically compact and is fully amenable to all current genetic tools. The field has made great progress since the discovery that families of olfactory receptor genes define many discrete channels of information providing the input to the olfactory bulb through glomeruli1. Still, there is no cohesive theory for how neural codes in the olfactory system build representations of odor features. This proposal approaches the question by proposing a model to link the representations on the input and output levels of the olfactory bulb and testing its predictions experimentally. Specifically, the project seeks to explain the source o the temporal structure observed in responses of the population of mitral and tufted cells (MTCs), each of which receives input from a single glomerulus, and which form the output of the bulb. Our core hypothesis is that the sequence in which an odor activates glomeruli directly influences the sign and timing of responses in the connected MTCs. Aim 1 tests the basic prediction of the model: that the earlier glomeruli in the spatiotemporal sequence activated by an odor will evoke mainly early, excitatory responses in the connected MTCs, while cells receiving input from later glomeruli will show a heterogeneous set of responses. Aim 2 will determine if this coding scheme holds over a range of concentrations, as the underlying mechanism in the model predicts. Aim 3 causally probes whether earlier activation of a glomerulus within the population decreases heterogeneity of responses of its MTCs. The proposed coding scheme has the potential to convey information about the identity of an odor in a way that is tolerant to changes in concentration. These ideas will be tested using recent technological advances in optogenetics and electrophysiology that allow the researchers to target and record odor activity from MTCs that are functionally connected to a specific glomerular channel. The proposed experiments will form the basis of the Primary Investigator's graduate dissertation work and will be carried out over the next 3 years. The Sponsor will provide guidance throughout the process, and particularly with the computational aspects and analyses. The work will be presented at scientific meetings and will be published and made available to the public when completed.