Learning-mediated plasticity in cortical feedback projections to the olfactory bulb

项目摘要/摘要 为了可靠地编码有关环境的信息，神经元必须修改它们的活动特征，甚至 准确解释复杂刺激的连通性。皮层对嗅球的反馈投射是 独特地定位于基于检测的处理(由感觉输入驱动)和 梨状皮质中的分析处理。这种安排使这些投影成为理想的目标 研究学习是如何重塑神经元活动图谱的。我已经开发了一种方法，它将允许 在小鼠学习一项任务时梨状皮质主要神经元轴突活动的综合分析 要求他们识别复杂混合物中嵌入的特定气味，从而提供对 嗅觉场景分析。我的方法还将详细分析大脑皮质之间的连通性 嗅球中的轴突及其突触后靶点，这将揭示嗅球如何整合 处理来自梨状皮质的信息。我要检验的假设是，学习会重塑大脑皮质 输入到嗅球，通过消除歧义导致增强的气味场景分割 嗅球输出神经元活动图谱。这些研究的结果将为我们提供新的见解 大脑将其刺激编码方案从对刺激的合成表示更新为分析表示 环境。这里提出的研究在技术上和概念上都是新颖的，结果将是 广泛适用于其他感官系统。在目标1中，我将描述学习如何塑造人的活动 皮质反馈投射到嗅球。目标2将决定突触的强度和数量 在学习过程中，对各个嗅觉模块的皮质输入进行更新。最后，目标3将决定如何 大脑皮层的输入形成了延髓输出神经元的活动轮廓。该奖项的培训阶段将是 由哈佛大学的Venkatesh Murthy教授和Naoshige Uchida教授的实验室进行。 与我的导师和咨询委员会一起，我制定了一个全面的培训计划，将 为我提供新的技术技能，并提供专业发展，使我能够成功 过渡到一个独立的调查员。该项目的建成将为今后的工作奠定基础 与嗅觉系统和其他感觉系统的学习调节可塑性有关的实验。

PROJECT SUMMARY/ABSTRACT To reliably encode information about the environment, neurons must modify their activity profiles and even connectivity to accurately interpret complex stimuli. Cortical feedback projections to the olfactory bulb are uniquely positioned at the interface between detection-based processing that is driven by sensory input and analytical processing occurring in the piriform cortex. This arrangement makes these projections an ideal target to study how learning reshapes neuronal activity profiles. I have developed an approach that will allow for a comprehensive analysis of the axonal activity of principal neurons in the piriform cortex, while mice learn a task requiring them to identify a specific odor embedded in complex mixtures, thereby providing unique insight into olfactory scene analysis. My approach will also provide a detailed analysis of the connectivity between cortical axons and their postsynaptic targets in the olfactory bulb, which will reveal how the olfactory bulb integrates processed information from the piriform cortex. The hypothesis I will test is that learning reshapes cortico-fugal input to the olfactory bulb, leading to enhanced odor-scene segmentation through the disambiguation of olfactory bulb output neuron activity profiles. The outcomes of these studies will provide novel insight to how the brain to updates its stimulus-encoding scheme from a synthetic to analytical representation of a stimulus environment. The studies proposed here are novel technically as well as conceptually, and the results will be broadly applicable to other sensory systems. In Aim 1, I will characterize how learning shapes the activity of cortical feedback projections to the olfactory bulb. Aim 2 will determine how the synaptic strength and number of cortical inputs to individual olfactory modules are updated during learning. Finally, Aim 3 will determine how cortical input shapes the activity profiles of bulbar output neurons. The training phase of this award will be conducted at Harvard University in the laboratories of Prof. Venkatesh Murthy and Prof. Naoshige Uchida. Together with my mentors and advisory committee, I have developed a comprehensive training plan that will provide me with new technical skills and provide professional development that will enable my successful transition to an independent investigator. The completion of this project will provide the basis for future experiments related to learning-mediated plasticity in the olfactory system and other sensory systems.