Precision of Myelin Plasticity in Health and Disease

项目摘要 我们的应用程序满足了专注于治疗多发性硬化症的科学界的基本需求 (毫秒)。MS是一种中枢神经系统炎症性疾病，影响着250多万人 原因不明的世界范围内。在对多发性硬化症的理解方面，由于缺乏 理解与行为相关的神经元活动和脑电活动变化之间的相互作用 髓鞘在健康和疾病中的作用。行为相关神经元活动和电路特异性之间的联系 髓鞘形成的变化尚不清楚，行为干预在促进髓鞘再生中的作用也是未知的。 最近，我们开发了新的方法来显示髓鞘、少突胶质细胞及其前体细胞。 完整的小鼠大脑，使人们能够前所未有地了解它们在健康和健康中的动态和行为 疾病。在这个应用中，我们建议利用个体间的、纵向的、亚细胞的洞察力 通过这些技术揭示局部电路活动和髓鞘形成对运动的影响 行为。这项建议的目标是：1)评估行为相关神经元回路的功能 调节学习过程中的髓鞘形成和髓鞘修复，以及2)阐明髓鞘特异性的变化 调节运动学习和行为。这一建议代表了一种新的研究方法的综合。 神经回路在行为和少突胶质细胞生物学中的作用，并在 了解脱髓鞘损伤后运动学习和功能障碍的机制。

Project Summary Our application addresses a fundamental need of the scientific community focused on curing Multiple Sclerosis (MS). MS is an inflammatory disease of the central nervous system that affects more than 2.5 million people worldwide with an unknown etiology. Progress in the understanding of MS has been constrained by a lack of understanding of the reciprocal interactions between behaviorally-relevant neuronal activity and changes in myelination in health and disease. The link between behaviorally-relevant neuronal activity and circuit-specific changes in myelination remain unknown, as does the role of behavior interventions in enhancing remyelination. Recently, we have developed new approaches to visualize myelin, oligodendrocytes, and their precursors in the intact mouse brain, allowing an unprecedented view into their dynamics and behavior in health and disease. In this application, we propose to capitalize on the inter-individual, longitudinal, subcellular insights revealed by these techniques to discern the effects of changes in local circuit activity and myelination on motor behavior. The objectives of this proposal are: 1) evaluate how behaviorally-relevant neuronal circuit function regulates myelination during learning and myelin repair and 2) to elucidate how changes in myelin specificity modulate motor learning and behavior. This proposal represents a novel synthesis of approaches to study neural circuit function during behavior and oligodendrocyte biology, and breaks new ground in the understanding of the mechanisms underlying motor learning and dysfunction following demyelinating injuries.