Precision of Myelin Plasticity in Health and Disease

项目摘要 我们的应用程序解决了科学界的基本需求，专注于治疗多发性硬化症 （MS）。MS是一种中枢神经系统的炎症性疾病，影响超过250万人 病因不明对多发性硬化症认识的进展受到缺乏 理解行为相关神经元活动和神经元活动变化之间的相互作用， 髓鞘形成在健康和疾病中的作用行为相关的神经元活动和特定回路之间的联系 髓鞘形成的变化仍然未知，行为干预在促进髓鞘再生中的作用也是未知的。 最近，我们已经开发了新的方法来可视化髓鞘，少突胶质细胞，以及它们的前体细胞。 完整的小鼠大脑，允许前所未有的观点，他们的动态和行为在健康和 疾病在这个应用程序中，我们建议利用个体间，纵向，亚细胞的见解 通过这些技术揭示了辨别局部回路活动和髓鞘形成变化对运动神经元的影响， 行为本研究的目的是：1）评估行为相关神经元回路的功能 在学习和髓鞘修复过程中调节髓鞘形成，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综合研究方法， 神经回路功能在行为和少突胶质细胞生物学，并开辟了新的领域， 了解脱髓鞘损伤后运动学习和功能障碍的潜在机制。

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.