PLASTICITY OF CORTICAL ENSEMBLE CONNECTIVITY IN VISUAL LEARNING

视觉学习中皮质整体连接的可塑性

• 批准号: 10693279
• 负责人: William Andrew Stoy
• 金额: $ 7.38万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2024-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693279
• 关键词: Address; Algorithms; Amblyopia; Behavior; Blindness; Brain; Calcium; Cells; Chronic; Compensation; Data; Discrimination; Disease; Economics; Electrodes; Electrophysiology (science); Exhibits; Holography; Human; Image; In Vitro; Individual; Intervention; Lead; Learning; Link; Maps; Measures; Methodology; Modality; Motion; Mus; Neocortex; Neurons; Neurophysiology - biologic function; Ocular Prosthesis; Optics; Pattern; Population; Property; Prosthesis; Reproducibility; Rewards; Robotics; Sensory; Stimulus; Structure; Structure-Activity Relationship; Synapses; Synaptic plasticity; Techniques; Technology; Testing; Time; Vision; Vision Disorders; Visual; Visual Cortex; Visual Perception; Visual System; Vocabulary; Work; area striata; effective therapy; in vivo; neocortical; neural; novel therapeutics; optogenetics; patch clamp; postsynaptic; presynaptic; response; sensory input; spatiotemporal; tool; two-photon; vision development; visual information; visual learning; visual process; visual processing; visual stimulus

Vision is a critical sensory modality that we depend on to navigate through the world and understand our surroundings. Disorders of the visual system lead to severe interpersonal deficits and to economic immiseration. Although much progress has been made describing the cellular basis of visual perception, little is known about the connectivity of brain circuits that process visual information, and even less is known about how this connectivity changes over time. I propose to leverage cutting-edge robotic and optical technologies to clarify how neuronal ensembles (coactive groups of cells) are connected in the primary visual cortex (V1), the neocortical region where visual perception arises. Ensembles in V1 exhibit activity patterns with reproducible spatial and temporal structures which define the functional vocabulary of cortical microcircuits. It has been recently shown that the activation of ensembles is necessary and sufficient for visual perception. The Hebbian hypothesis suggests that neurons that are repeatedly coactive over time (ensembles) are likely to be more strongly synaptically connected to one another than to neurons outside of the ensemble. I will develop a high-throughput tool to test this Hebbian hypothesis of preferential synaptic connectivity within ensembles using robotic electrophysiology and holographic optogenetic stimulation (Aim 1). I will then describe the functional and structural changes of cortical microcircuits during visual learning using chronic two-photon calcium imaging of neurons in the mouse visual cortex, in relation to the Hebbian hypothesis of synaptic plasticity and learning (Aim 2). Successful completion the current project will establish a structural link between ensemble activity and the activity of the brain during visual learning, yielding inroads towards a more complete understanding of visual processing, a prerequisite to addressing the dearth of effective treatment options for blindness.

视觉是一种重要的感官形式，我们依靠它来浏览世界并了解我们的生活。 四周视觉系统障碍导致严重的人际交往障碍和经济困难。 不幸虽然在描述视觉的细胞基础方面已经取得了很大进展， 人们对处理视觉信息的大脑回路的连通性知之甚少， 我们知道这种连通性是如何随时间变化的。我建议利用尖端的机器人和 光学技术，以澄清神经元集合（细胞的共同活动组）是如何连接在 初级视觉皮层（V1），即产生视觉感知的新皮层区域。V1展览中的合奏 活动模式与可再现的空间和时间结构，定义功能词汇 大脑皮层微电路最近的研究表明，合奏的激活是必要的， 足够的视觉感知。赫布假说认为，神经元， 随着时间的推移，相互作用（集合）可能比彼此之间的突触连接更强烈 到群体之外的神经元。我将开发一个高通量的工具来测试这个赫布假说 使用机器人电生理学和全息技术， 光遗传学刺激（Aim 1）。然后，我将描述皮层的功能和结构变化， 用慢性双光子钙离子成像研究小鼠视觉学习过程中的微电路 视觉皮质，与突触可塑性和学习的赫布假说有关（目的2）。成功 完成目前的项目将建立一个整体活动和活动之间的结构联系， 大脑在视觉学习过程中，产生对视觉更完整的理解的进展 这是解决失明有效治疗方案缺乏问题的先决条件。