Role of neuronal ensembles in cortical plasticity during learning and development

项目概要/摘要 大脑在发育过程中经历了广泛的突触可塑性和回路细化。类似 在整个生命过程中，变化会以一种更狭隘的方式在学习过程中反复发生。了解如何 神经元的连接和活动被适应性地重塑，以适应不断变化的世界， 神经科学研究中最突出的问题。最近的技术创新提供了前所未有的机会 来解决这个问题在这里，该建议的重点是电路机制，重新配置神经元合奏， 小鼠初级视皮层（V1）在发育和学习过程中的变化。为了响应视觉需求，皮层 集合改变它们的响应特性以“给予”视觉空间中的相关特征显著性。使用体积 双光子（2 P）显微镜，候选人将纵向跟踪V1中数千个神经元的活动， 在整个视觉学习过程中，候选人将使用空间光调制器（SLM） 激活和特异性功能和/或分子定义的神经元亚群， 揭示了皮层可塑性的基础电路元件。第二，掌握了“全光学”方法， 记录和询问神经元，候选人将研究一个特定的发育活动期的作用， 在建立皮层集合的方向调谐中起作用，并探索消除这种计算如何改变 视觉感知该项目的成功完成将为电路机制提供新的见解， 在神经元活动中建立稳态，同时产生足够的灵活性以适应 学习当这种平衡被破坏时，许多神经病理状态就会出现。更好地了解 生理回路功能无疑先于并将有助于新疗法的发展 来治疗神经系统疾病最后，这项工作将定位候选人建立一个独立的 一个研究项目，询问来自发育中的硬连线感觉电路的信息是如何 与可延展的皮质集合体汇合以产生视觉引导的行为。

Project Summary/Abstract The brain undergoes extensive synaptic plasticity and circuit refinement during development. Similar changes recur throughout life during learning in a more narrowly constrained manner. Understanding how neuronal connections and activity are adaptively remodeled to accommodate a changing world remains an outstanding question in neuroscience research. Recent technological innovations provide unprecedented access to address this. Here, the proposal focuses on the circuit mechanisms that reconfigure neuronal ensembles in mouse primary visual cortex (V1) during development and learning. In response to visual demands, cortical ensembles shift their response properties to “give” salience to relevant features in visual space. Using volumetric two-photon (2P) microscopy, the candidate will longitudinally track the activity of thousands of neurons in V1, with single-cell resolution, throughout visual learning. The candidate will then use a spatial light modulator (SLM) to activate and inactivate specific functionally and/or molecularly defined subpopulations of neurons to causally uncover circuit elements that underlie cortical plasticity. Second, having mastered an “all-optical” approach to record and interrogate neurons, the candidate will study the role that a specific developmental activity period plays in establishing orientation tuning in cortical ensembles and probe how eliminating this computation alters visual perception. Successful completion of this project will provide new insights to the circuit mechanisms that establish homeostasis in neuronal activity while simultaneously yielding sufficient flexibility to accommodate learning. Many neuropathological states arise when this balance is disrupted. A greater understanding of physiological circuit function undoubtedly precedes, and will contribute to, the development of novel therapeutics to treat disorders of the nervous system. Finally, this work will position the candidate to establish an independent research program which interrogates how information from developmentally hardwired sensory circuits converges with malleable cortical ensembles to generate visually-guided behaviors.