Circuitry Mechanisms of Enhanced Visual Plasticity During Locomotion

项目总结/摘要 发育中的视觉皮层具有显著的可塑性，能够表现出长期的变化。 它的神经元反应以适应外部环境。然而，这种经验依赖 可塑性在成年动物中变得不那么突出，导致学习能力降低， 脑损伤的不完全恢复。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。最近的研究表明，跑步是 有效地增强动物和人类的成年脑功能和视觉可塑性。 因此，拟议的研究旨在剖析底层电路，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性理解 促进康复和视觉感知学习。我将描述皮质内回路的特征， 皮层下神经调节系统参与皮层可塑性，新的和多学科的 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，拟议的研究将侧重于局部抑制回路， 有助于增强运动依赖性视觉可塑性过程中的视觉反应。 利用转基因小鼠模型和双光子钙成像，我将测量 不同类型的抑制性神经元的活动模式，特别是研究较少的VIP和SST interneurons，在单细胞分辨率跟踪其纵向变化过程中的视觉可塑性。我会 我也学会利用光遗传学，连同膜片钳，以确定如何具体的抑制， 输入将有助于兴奋性神经元亚群中的视觉增强。在 在这个奖项的独立阶段，我希望领导一个研究小组，以确定神经调节 这些系统在驱动可塑性方面发挥着重要作用。通过病毒追踪和脑深部成像 来识别传递运动相关信息的皮层下投射路径。我会把联合收割机 活体光遗传学和高密度电生理记录来研究神经调节系统， 特别是长期被质疑的血清素，影响皮层处理并导致皮层可塑性。 从长远来看，我希望了解相互关联的大脑回路如何整合以调节视觉 活动和可塑性，知觉学习和康复的基本基础， 病理条件。斯特赖克博士是世界著名的视觉可塑性专家和著名的导师 支持年轻的科学家。与Sohal博士一起，UCSF的两个实验室是一个 理想的环境，为拟议的项目，这将为我提供丰富的资源， 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，以过渡到一个强大的独立研究人员。

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.