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质感觉表征，但在发育之后 塑性的成熟能力变得有限。受严格控制的成熟皮质的可塑性使 学习，但会阻碍大脑在受伤、中风或感觉延长后恢复适当功能的能力 损失。研究成人阶段知觉学习的基础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 大脑。树鼠(Tupaia Belangeri)的最新研究，这种高度视觉的哺乳动物分享大脑皮层 灵长类动物的组织特征表明，学习基于奖励的定向辨别任务会导致 兴奋性反应的长期变化提高了任务相关刺激之间的区分性 成熟初级视皮层(V1)。然而，我们对潜在的电路机制缺乏清楚的了解 对这些变化负有责任。我将结合我以前研究突触机制的经验 新的培训侧重于扩展我在尖端光学方法方面的技术专长，以 揭示树精知觉学习的潜在机制。初步数据显示， 在兴奋性改变之前，抑制性网络反应的暂时性和特异性下降 神经元群与增强的表现相关，表明树鼠V1的学习过程 第2/3层是一个精确的层，其中电路元件同时具有特性和时间特性。这就做 将慢性双光子成像与新型基因增强剂和精密RNAScope相结合 检测V1抑制神经亚群反应特性变化的技术 知觉学习(目标1)。此外，我还将定义兴奋性神经元功能性突触结构的变化。 经历学习相关变化的神经元(目标2)--通过应用树突棘的钙成像 学习过程。最后，我将建立乙酰胆碱释放的时空招募 通过利用最近开发的胆碱能传感器的优势进行辨别学习(目标3) 通过学习阶段慢性成像。这个项目充分利用了树的功能组织 Shrew V1区域作为一个独特的模型来解决如何在高度结构化的大脑皮层中实施知觉学习 网络与灵长类皮质中发现的网络相似。研究将在以下地点的协作环境中进行 马克斯·普朗克佛罗里达神经科学研究所(MPFI)以开发创新的方法来解决 关于神经回路的基本问题，以及世界上为数不多的树鼠栖息地之一。 完成这些目标和培训计划将产生一个描述进展的全面框架 我将在此基础上进行一项独立的研究 未来的计划。

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.