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Role of neuronal ensembles in cortical plasticity during learning and development

神经元群在学习和发展过程中皮质可塑性中的作用

基本信息

批准号：
10688120
负责人：
Alejandro Akrouh
金额：
$ 14.32万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10688120
关键词：
Address Behavior Behavioral Benchmarking Brain Calcium Cells Chronic Cognition Collaborations Development Discrimination Disease Elasticity Elements Equilibrium Exhibits Eye Future Genetic Holography Homeostasis Image Interneurons Investigation Lasers Learning Life Light Link Maps Mediating Microscopy Molecular Motor Mus Nervous System Neurons Neurosciences Research Optics Pattern Perception Periodicals Phase Physiological Play Population Positioning Attribute Property Recurrence Research Resolution Retina Rewards Role Sensory Shapes Somatostatin Stereotyping Stimulus Synaptic plasticity Testing Training Vision Visual Visual Perception Visual System Vocabulary Work area striata behavioral response cognitive process excitatory neuron flexibility hippocampal pyramidal neuron inhibitory neuron insight neonatal mice nervous system disorder neural neural circuit neuropathology novel novel therapeutics optogenetics orientation selectivity preference programs receptive field response technological innovation theories therapeutic development tool two-photon visual learning

项目摘要

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.

项目概要/摘要大脑在发育过程中经历广泛的突触可塑性和电路细化。相似的在学习过程中，变化会以更严格的限制方式在一生中反复出现。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，该提案重点关注重新配置神经元集合的电路机制发育和学习期间的小鼠初级视觉皮层（V1）。为了响应视觉需求，皮质集成改变了它们的响应属性，以“赋予”视觉空间中相关特征的显着性。使用体积双光子 (2P) 显微镜，候选人将纵向追踪 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。然后，候选人将使用空间光调制器（SLM）激活和失活特定功能和/或分子定义的神经元亚群，以因果关系揭示皮层可塑性背后的电路元件。其次，掌握了“全光学”方法记录和询问神经元，考生将研究特定发育活动时期的作用在皮质系综中建立方向调整，并探讨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建立神经元活动的稳态，同时产生足够的灵活性以适应学习。当这种平衡被破坏时，就会出现许多神经病理状态。更深入地了解生理回路功能无疑先于新疗法的发展，并将有助于新疗法的发展治疗神经系统疾病。最后，这项工作将使候选人能够建立一个独立的研究项目询问来自发育性硬连线感觉回路的信息如何与可延展的皮质整体融合，产生视觉引导的行为。