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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要正在发育的视觉皮层具有显着的可塑性，能够表现出长期的变化其神经元的反应是为了适应外部环境。然而，这种依赖经验的可塑性在成年动物中变得不那么突出，导致学习能力下降和脑损伤未完全恢复。因此，找到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增强动物和人类的成人大脑功能和视觉可塑性。因此，所提出的研究旨在剖析底层电路以揭示其原理控制大脑可塑性并为潜在的治疗干预提供机制理解促进康复和视知觉学习。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，具有新颖性和多学科性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，拟议的研究将重点关注局部抑制回路有助于增强运动依赖性视觉可塑性期间的视觉响应能力。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，尤其是研究较少的 VIP 和 SST 中间神经元，以单细胞分辨率跟踪其在视觉可塑性过程中的纵向变化。我会还学习利用光遗传学和膜片钳技术来确定特异性抑制作用输入将有助于兴奋性神经元亚群的视觉增强。在独立阶段的奖项，我希望带领一个研究团队来精确定位神经调节在推动可塑性方面发挥重要作用的系统。通过病毒追踪和深部脑成像，我的目标是识别传达运动相关信息的皮层下投射路径。我将结合在体内光遗传学和高密度电生理学记录来研究神经调节系统，特别是长期受到质疑的血清素，会影响皮质加工并导致皮质可塑性。从长远来看，我希望了解互连的大脑回路如何整合来调节视觉活动性和可塑性，是正常和正常情况下知觉学习和康复的基本基础病理状况。 Stryker 博士是世界著名的视觉可塑性专家和著名导师用于造林和支持年轻科学家。加州大学旧金山分校的两个实验室与 Sohal 博士一起，拟议项目的理想环境，将为我提供丰富的资源，实质性的技术支持和宝贵的见解，以确保成功完成研究和职业发展培训，帮助转变为一名强大的独立研究员。