Local slow wave sleep in repair and recovery after stroke

这个指导性职业发展奖的目标是帮助候选人过渡到独立 作为一名研究可塑性、睡眠和中风之间关系的医师科学家。候选人是医学博士， 睡眠神经学家博士，拥有工程学、人类睡眠电生理学及其与睡眠的关系背景 大脑的可塑性。该奖项将帮助候选人获得基础遗传、分子和体内的经验 成像技术以及对参与的细胞和分子机制的深入了解 可塑性介导的神经元修复。该奖项将帮助候选人成为一名独立医生 科学家利用睡眠来加快科学发现的步伐及其在护理方面的应用 患有神经系统疾病的人。该职业发展奖汇集了三位专家，涵盖以下领域： 睡眠的不同领域（Landsness – PI）、大脑恢复的可塑性（Lee – Mentor）和光学神经影像 （卡尔弗 - 导师）来解决这个创新概念，并有可能开辟一个新的研究领域。研究 设立该职业发展奖的环境非常出色。 Jin Moo Lee 博士，翻译家 神经科学家和血管神经学家，对中风恢复的可塑性感兴趣，拥有长期的记录 科学和指导的成功。 Joe Culver 博士是 Lee 实验室的长期合作者，高度评价 对候选人将使用的成像技术有丰富的经验。最后，华盛顿大学神经科学 社区强调高质量的研究、年轻教师的职业发展和协作，所有关键 他的成功。 该提案的一个目标是了解慢波睡眠 (SWS) 在术后修复和恢复中的作用 局灶性缺血性脑损伤。局部 SWS 对于与学习相关的大脑可塑性至关重要。涉及的机制 大脑可塑性被认为是脑损伤后成功的神经修复和恢复所必需的。 最近已证明生长抑素能中间神经元 (SOMi) 的神经元活动对 SWS 具有重要调节作用。 我们建议 1) 确定全局 SWS 在局灶性缺血后脑修复小鼠模型中的作用 （光血栓形成）在体感皮层，2）局部操纵 SWS（通过 SOMi 使用化学遗传学） 确定调节局部 SWS 是否会影响皮质重映射、突触发生和感觉运动恢复。 如果假设正确，它将表明局部操纵 SWS 可以选择性地驱动可塑性和 最终从中风中康复。它还将确定 SOMi 是否适合定位并可能提供帮助 制定一种新的治疗方法来增强中风后的可塑性和恢复。这个职业 发展奖是候选人获得基础研究重要培训的理想平台 技术，加深他对SWS在中风修复和恢复中的作用的理解，并将让他启动 致力于独立研究生涯，专注于利用睡眠来帮助护理中风患者。

The goal of this mentored career development award is to enable the candidate’s transition to independence as a physician-scientist studying the connection between plasticity, sleep and stroke. The candidate is an MD, PhD sleep neurologist with a background in engineering, human sleep electrophysiology and how it relates to brain plasticity. The award will help the candidate gain experience in basic genetic, molecular and in-vivo imaging techniques as well as an in-depth knowledge of the cellular and molecular mechanisms involved in plasticity mediated neuronal repair. This award will help the candidate to become an independent physician scientist using sleep as way to accelerate the pace of scientific discovery and its application to the care of individuals with neurological disease. This career development award brings together three experts covering the diverse fields of sleep (Landsness – PI), plasticity of brain recovery (Lee – Mentor) and optical neuroimaging (Culver – Mentor) to tackle this innovative concept and potentially open-up a new field of research. The research environment in which this career development award is proposed is outstanding. Dr. Jin Moo Lee, a translational neuroscientist and vascular neurologist with an interest in the plasticity of stroke recovery, has a long track record of both scientific and mentorship success. Dr. Joe Culver, is a long-time collaborator of the Lee lab and highly experienced in the imaging techniques the candidate will use. Finally, the Washington University neuroscience community emphasizes high quality research, career development of young faculty and collaboration, all keys to his success. An objective of this proposal is to understand the role of slow wave sleep (SWS) in repair and recovery after focal ischemic brain injury. Local SWS is critical for learning-related brain plasticity. Mechanisms involved in brain plasticity have been postulated to be necessary for successful neural repair and recovery after brain injury. Neuronal activity in somatostatinergic interneurons (SOMi) has recently been shown to critically mediate SWS. We propose to 1) determine the role of global SWS in a mouse model of brain repair following focal ischemia (photothrombosis) in somatosensory cortex and 2) locally manipulate SWS (via SOMi using chemogenetics) to determine if modulating local SWS affects cortical remapping, synaptogenesis, and sensorimotor recovery. If the hypothesis is correct, it will show that locally manipulating SWS can selectivity drive plasticity and ultimately recovery from stroke. It will also determine if SOMi might be amenable to targeting and may help shape a novel therapeutic approach to enhancing plasticity and recovery following stroke. This career development award is the ideal platform for the candidate to acquire important training in basic research techniques, deepen his understanding of the role SWS in repair and recovery of stroke, and will launch him towards an independent research career focused on using sleep to aid in care of individuals suffering from stroke.