Role of neuronal ensembles in cortical plasticity during learning and development

项目摘要/摘要 大脑在发育过程中经历了广泛的突触可塑性和电路精炼。类似 在学习的过程中，变化会以一种更狭隘的方式在一生中反复发生。了解如何 神经元连接和活动被适应性地重塑，以适应不断变化的世界 神经科学研究中的突出问题。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，该提案集中在重新配置神经元集合的电路机制上 发育和学习过程中的小鼠初级视皮层(V1)。作为对视觉需求的响应，皮质 合奏改变了它们的反应特性，使视觉空间中的相关特征“突出”起来。使用体积 双光子(2P)显微镜，候选者将纵向跟踪V1中数千个神经元的活动， 具有单细胞分辨率，贯穿整个视觉学习过程。然后，候选人将使用空间光调制器(SLM) 激活和失活特定的功能和/或分子定义的神经元亚群 发现构成皮质可塑性的电路元件。第二，掌握了一种“全光”的方法 记录和询问神经元，考生将研究特定发育活动期的作用 在建立大脑皮层集合中的定向调整方面发挥了作用，并探讨了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动态平衡，同时产生足够的灵活性来适应 学习。当这种平衡被打破时，许多神经病理状态就会出现。更好地理解 生理回路功能无疑领先于并将有助于新疗法的发展 治疗神经系统疾病。最后，这项工作将把候选人定位为建立独立的 一种研究程序，它询问来自发育硬连接感觉电路的信息是如何 与可延展的皮质合奏融合，以产生视觉引导行为。

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.