An Origin of Temporal Coding in the Early Olfactory System

 描述（由申请人提供）：神经科学领域的一个基本目标是了解大脑如何处理感觉信息。了解神经元在正常条件下如何代表感觉刺激，可以识别病理情况下受损的成分，并制定具体的，有针对性的策略来治疗它们。啮齿类动物的嗅觉系统具有许多独特的优势来探测感觉编码方案，包括它在解剖学上是紧凑的，并且完全适合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，通过肾小球向嗅球提供输入信息以来，该领域取得了很大进展。然而，对于嗅觉系统中的神经代码如何构建气味特征的表征，还没有一个内聚理论。这个提议通过提出一个模型来连接嗅球的输入和输出水平的表示，并通过实验来测试其预测。具体而言，该项目旨在解释在二尖瓣和簇状细胞（MTCs）群体的反应中观察到的时间结构的来源，每个MTCs都从单个肾小球接收输入，并形成灯泡的输出。我们的核心假设是，气味激活肾小球的顺序直接影响相关MTCs的反应信号和时间。目的1测试的基本预测模型：早期肾小球在时空序列中激活的气味将引起主要是早期，兴奋性反应，在连接的MTCs，而细胞接收输入从后来的肾小球将显示一组异质性的响应。目标2将确定这种编码方案是否在一定浓度范围内保持不变，正如模型中的潜在机制所预测的那样。目的3因果关系探讨是否早期激活的肾小球内的人口减少其MTCs的反应的异质性。建议的编码方案有可能传达信息的身份的气味的方式，是容忍的浓度变化。这些想法将使用光遗传学和电生理学的最新技术进展进行测试，这些技术进展使研究人员能够靶向并记录功能上与特定肾小球通道连接的MTCs的气味活动。拟议的实验将构成主要研究者的研究生论文工作的基础，并将在未来3年内进行。申办者将在整个过程中提供指导，特别是计算方面和分析。这项工作将在科学会议上提出，完成后将出版并向公众提供。

 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.