Circuitry Mechanisms of Enhanced Visual Plasticity During Locomotion

运动过程中增强视觉可塑性的电路机制

• 批准号: 10213933
• 负责人: Yujiao Jennifer Sun
• 金额: $ 5.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213933
• 关键词: Acute; Adolescent; Adult; Affect; Animals; Area; Automobile Driving; Award; Axon; Biological; Brain; Brain Injuries; Brain imaging; Calcium; Cell Nucleus; Cells; Cues; Development; Dorsal; Electrophysiology (science); Ensure; Environment; Exhibits; Fiber; Human; Image; Imaging Techniques; Injections; Instruction; Interneurons; Label; Lead; Learning; Locomotion; Measures; Mentors; Modification; Mus; Neurons; Parvalbumins; Pathologic; Pathway interactions; Pattern; Perceptual learning; Phase; Photometry; Play; Process; Property; Recovery; Rehabilitation therapy; Research; Research Personnel; Resolution; Resources; Rodent; Role; Running; Scientist; Serotonin; Signal Transduction; Slice; Somatostatin; Stimulus; System; Therapeutic Intervention; Training; Vasoactive Intestinal Peptide; Viral; Vision; Visual; Visual Cortex; Work; area striata; career development; cell type; cholinergic; density; excitatory neuron; experience; forest; in vivo; inhibitory neuron; insight; interdisciplinary approach; learning ability; mature animal; microendoscope; monocular; mouse model; neural circuit; neuromechanism; neuroregulation; novel strategies; optogenetics; patch clamp; relating to nervous system; research and development; response; two-photon; visual plasticity

PROJECT SUMMARY/ABSTRACT The developing visual cortex is remarkably plastic, capable of exhibiting a long-term modification of its neuronal responses to adapt to the external environment. However, this experience-dependent plasticity becomes much less prominent in the adult animal, responsible for reduced learning ability and incomplete recovery from brain injury. Therefore, it is critical to identify ways to enhance adult plasticity and elucidate its underlying neural mechanism. Recent works have demonstrated that running is effective in enhancing adult brain functions and visual plasticity in animals and human beings. Therefore, the proposed research aims to dissect the underlying circuit to uncover the principle governing brain plasticity and provide a mechanistic understanding for potential therapeutic intervention to promote rehabilitation and visual perceptual learning. I will characterize the intracortical circuit and subcortical neuromodulatory system involved in cortical plasticity, with novel and multidisciplinary approaches including state-of-the-art imaging techniques, optogenetics, and electrophysiology. In the mentored phase of the award, the proposed study will focus on local inhibitory circuit that contributes to the enhanced visual responsiveness during locomotion-dependent visual plasticity. Taking advantage of transgenetic mouse models and two-photon calcium imaging, I will measure the activity patterns in different types of inhibitory neurons, especially the less studied VIP and SST interneurons, at single-cell resolution to track their longitudinal changes during visual plasticity. I will also learn to utilize optogenetics, together with patch clamping, to determine how specific inhibitory inputs will contribute to visual enhancement in a subpopulation of excitatory neurons. In the independent stage of the award, I hope to lead a research team to pinpoint the neuromodulatory systems that play an essential role in driving plasticity. With viral tracing and deep-brain imaging, I aim to identify subcortical projecting pathways that convey locomotion-related information. I will combine in vivo optogenetics and high-density electrophysiology recording to study how neuromodulatory systems, particularly the long-questioned serotonin, affect cortical processing and leads to cortical plasticity. In the long term, I hope to understand how interconnected brain circuits integrate to modulate visual activity and plasticity, the fundamental basis for perceptual learning and rehabilitation in normal and pathological conditions. Dr. Stryker is a world-prominent expert in visual plasticity and a reputed mentor for foresting and supporting young scientists. Together with Dr. Sohal, the two labs at UCSF are an ideal environment for the proposed projects, which will provide me with abundant resources, substantial technical supports, and invaluable intellectual insights to ensure the successful completion of the research and career development training for transitioning into a potent independent researcher.

项目摘要/摘要 发展中的视觉皮层非常塑料，能够长期修改 它对适应外部环境的神经元反应。但是，这种依赖于经验 在成年动物中，可塑性变得不那么突出，负责降低学习能力和 从脑损伤中恢复不完全。因此，确定增强成人可塑性的方法至关重要 并阐明其潜在的神经机制。最近的作品表明跑步是 有效增强动物和人类的成人脑功能和视觉可塑性。 因此，拟议的研究旨在剖析基础电路以发现原理 管理大脑可塑性并为潜在的治疗干预提供机械理解 促进康复和视觉感知学习。我将表征心脏内电路和 皮质可塑性涉及的皮质下神经调节系统，具有新颖和多学科 包括最先进的成像技术，光遗传学和电生理学的方法。 在奖励的指导阶段，拟议的研究将重点放在本地抑制回路上 在运动依赖性视觉可塑性过程中有助于增强的视觉响应能力。 利用转基因小鼠模型和两光子钙成像，我将测量 不同类型的抑制性神经元中的活性模式，尤其是研究较少的VIP和SST 中间神经元，以单细胞分辨率来跟踪其在视觉可塑性期间的纵向变化。我会 还要学会利用光遗传学以及斑块夹紧，以确定特定的抑制作用 输入将有助于兴奋性神经元亚群的视觉增强。在 该奖项的独立阶段，我希望领导一个研究团队来指出神经调节 在驱动可塑性中起着至关重要的作用的系统。通过病毒追踪和深度脑成像，我的目标 确定传达与运动相关信息的皮质下投影途径。我将结合 体内光遗传学和高密度电生理记录，以研究神经调节系统如何， 特别是长期提出的5-羟色胺，影响皮质加工并导致皮质可塑性。 从长远来看，我希望了解如何整合互连的脑电路以调节视觉 活动和可塑性，正常学习和康复的基本基础 病理状况。 Stryker博士是视觉可塑性的全球主要专家，也是知名的导师 用于森林和支持年轻科学家。与苏哈尔博士一起，UCSF的两个实验室是 拟议项目的理想环境，这将为我提供丰富的资源，大量资源 技术支持和宝贵的知识见解，以确保成功完成 研究和职业发展培训，用于过渡到有效的独立研究人员。