Circuit dynamics underlying perceptual learning in the functionally organized visual cortex

项目摘要 在发育过程中，经验以一种显著的方式塑造了皮层的感觉表征， 可塑性的成熟能力变得有限。成熟大脑皮层的可塑性受到严格控制， 学习，但阻碍大脑的能力，以恢复适当的功能后，受伤，中风或长期的感觉 损失研究成人阶段知觉学习的基本机制将促进我们的理解 并将为开发促进成人可塑性的新方法提供基础 个脑袋最近的研究在树（树鼩 belangeri），一个高度视觉的哺乳动物，分享皮层 灵长类动物的组织特征表明，学习基于奖励的方向辨别任务会导致 兴奋性反应的长期持续变化，增加了任务相关刺激之间的辨别力， 成熟的初级视皮层（V1）。然而，我们缺乏对潜在电路机制的清晰理解 这些变化的罪魁祸首我将联合收割机我以前研究突触机制的经验， 可塑性与新的培训，重点是扩大我的技术专长，在尖端光学方法， 揭示树鼩感知学习的潜在机制。初步数据显示， 抑制性网络反应的短暂和特征特异性降低先于兴奋性网络反应的变化。 神经元群体与增强的性能，表明学习过程中，在树鼩 V1 层2/3是精确层，其中电路元件与特征和时间特异性接合。我会 采用慢性双光子成像与新型遗传增强剂和精确的RNA显微镜相结合 技术，以确定V1抑制性神经亚群的反应特性的变化， 感知学习（目标1）。此外，我将定义兴奋性神经元的功能性突触结构的变化， 神经元经历学习相关的变化（目的2）通过应用钙成像的树突棘， 学习过程。最后，我将建立乙酰胆碱释放的时空募集过程中， 辨别学习（目标3），利用最近开发的胆碱能传感器，可以 通过学习阶段长期成像。这个项目利用了树的功能组织 Shrew V1区作为一个独特的模型，以解决感知学习是如何在高度结构化的皮层 类似于灵长类动物大脑皮层的网络。这些研究将在一个合作的环境中进行， 马克斯·普朗克佛罗里达神经科学研究所（MPFI）以开发创新方法解决 关于神经回路的基本问题，以及世界上为数不多的树鼩栖息地之一。 完成这些目标和培训计划将导致一个全面的框架，描述进展情况 在功能结构皮层中与学习相关的可塑性，我将在此基础上建立一个独立的研究 计划在未来。

Project Summary Experience shapes cortical sensory representations in a remarkable manner during development, but after maturation capacity for plasticity becomes limited. The tightly regulated plasticity of the mature cortex enables learning but impedes the brain’s capacity to regain appropriate function after injury, stroke or prolonged sensory loss. Studying mechanisms that underlie perceptual learning in the adult stage will advance our understanding of perception and will provide the foundation to develop novel approaches that promote plasticity in the adult brain. Recent studies in the tree shrew (tupaia belangeri), a highly visual mammal that shares cortical organization features with primates, show that learning a reward-based orientation discrimination task leads to long lasting changes in excitatory responses that increase discriminability between task relevant stimuli in the mature primary visual cortex (V1). However, we lack a clear understanding of the underlying circuit mechanisms that are responsible for these changes. I will combine my previous experience studying mechanisms of synaptic plasticity with new training focused on expanding my technical expertise in cutting edge optical approaches to uncover the mechanisms underlying perceptual learning in the tree shrew. Preliminary data suggest that a transient and feature specific decrease in the inhibitory network response precedes changes in the excitatory neuronal population associated with enhanced performance, showing that the learning process in tree shrew V1 layer 2/3 is a precise one where circuit elements are engaged with both feature and temporal specificity. I will employ chronic 2-photon imaging in combination with novel genetic enhancers and precise RNAscope technology to determine changes in the response properties of V1 inhibitory neural subpopulations during perceptual learning (Aim 1). Additionally, I will define changes in the functional synaptic architecture of excitatory neurons that undergo learning-related changes (Aim 2) by applying calcium imaging of dendritic spines through the learning process. Finally, I will establish the spatiotemporal recruitment of acetylcholine release during discrimination learning (Aim 3) by taking advantage of a recently developed cholinergic sensor that can be imaged chronically through learning stages. This project capitalizes on the functional organization of the tree shrew V1 area as a unique model to address how perceptual learning is implemented in highly structured cortical networks akin to those found in the primate cortex. The studies will take place in a collaborative environment at Max Planck Florida Institute for Neuroscience (MPFI) known for developing innovative approaches to address fundamental questions about neural circuits and hosting one of the few tree shrew colonies in the world. Completion of these aims and training plan will lead to a comprehensive framework describing the progression of learning-related plasticity in a functionally structured cortex upon which I will build an independent research program in the future.