Circuitry Mechanisms of Enhanced Visual Plasticity During Locomotion

项目摘要/摘要 发育中的视皮层具有显著的可塑性，能够表现出长期的 它的神经元反应，以适应外部环境。然而，这种经验依赖于 成年动物的可塑性变得不那么明显，这是学习能力下降和 未完全从脑损伤中恢复。因此，找出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。最近的研究表明，跑步是 能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潜在的电路，以揭示其原理 控制大脑的可塑性并为潜在的治疗干预提供机制理解 促进康复和视觉知觉学习。我将描述大脑皮质内回路的特征 皮质下神经调节系统参与皮质可塑性，具有新颖性和多学科 方法包括最先进的成像技术、光遗传学和电生理学。 在该奖项的指导阶段，拟议的研究将集中在局部抑制回路 有助于在运动依赖的视觉可塑性过程中增强视觉反应能力。 利用转基因小鼠模型和双光子钙成像，我将测量 不同类型抑制性神经元的活动模式，特别是研究较少的VIP和SST 中间神经元在单细胞分辨率下跟踪它们在视觉可塑性过程中的纵向变化。这就做 还要学习利用光遗传学和膜片钳技术来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 在独立阶段的颁奖中，我希望带领一个研究团队来准确地研究神经调节 在推动可塑性方面发挥重要作用的系统。通过病毒追踪和脑深部成像，我的目标是 识别传递运动相关信息的皮质下投射通路。我会加入的 活体光遗传学和高密度电生理记录，以研究神经调节系统， 尤其是长期受到质疑的5-羟色胺，会影响大脑皮层的加工，导致大脑皮层可塑性。 从长远来看，我希望了解相互连接的大脑回路是如何整合来调节视觉的 活动性和可塑性，是正常和正常儿童知觉学习和康复的基本基础 病理情况。史崔克博士是世界著名的视觉可塑性专家，也是著名的导师。 来支持和支持年轻的科学家。与索哈尔博士一起，加州大学旧金山分校的两个实验室是 建议项目的理想环境，这将为我提供充裕的资源，可观的 技术支持和宝贵的智力见解，以确保成功完成 研究和职业发展培训，以过渡到一个强有力的独立研究人员。

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.