Local slow wave sleep in repair and recovery after stroke

这个辅导式职业发展奖的目标是使候选人能够过渡到独立 作为一名研究可塑性、睡眠和中风之间联系的内科科学家。候选人是医学博士， 睡眠神经科博士，具有工程学、人类睡眠电生理学及其与 大脑的可塑性。该奖项将帮助候选人获得基础遗传学、分子和体内实验方面的经验 成像技术以及对细胞和分子机制的深入了解 可塑性介导的神经元修复。这个奖项将帮助候选人成为一名独立的医生 科学家以睡眠为手段加快科学发现的步伐及其在护理中的应用 患有神经系统疾病的个体。这个职业发展奖汇集了三位专家，他们涵盖了 睡眠的不同领域(Landsness-PI)、脑恢复的可塑性(Lee-Mentor)和光学神经成像 (卡尔弗-导师)致力于解决这一创新概念，并可能开辟一个新的研究领域。这项研究 这个职业发展奖的评选环境非常出色。李金武博士，翻译 神经学家和血管神经学家对中风康复的可塑性感兴趣，有着长期的记录 无论是科学还是导师的成功。乔·卡尔弗博士是李实验室的长期合作者，他高度重视 在应聘者将使用的成像技术方面经验丰富。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合作，所有这些都是关键 为他的成功干杯。 这项建议的一个目的是了解慢波睡眠(SWS)在修复和康复中的作用 局灶性脑缺血损伤。局部短波对学习相关的大脑可塑性至关重要。涉及的机制 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。 生长抑素能中间神经元(Somi)的神经元活动在SWS中起重要作用。 我们建议1)确定全局SWS在局灶性脑缺血后小鼠脑修复模型中的作用 (光血栓)在躯体感觉皮质和2)局部操纵SWS(通过使用化学遗传学的Somi)以 确定调节局部SWS是否影响皮质重新映射、突触发生和感觉运动恢复。 如果假设是正确的，它将表明，局部操纵SWS可以选择性地驱动可塑性和 最终从中风中恢复过来。它还将确定Somi是否可以接受目标，并可能有所帮助 塑造一种新的治疗方法，以增强中风后的可塑性和康复。这份职业 发展奖是候选人获得重要基础研究培训的理想平台 技术，加深他对SWS在中风修复和康复中的作用的理解，并将启动他 迈向一个独立的研究生涯，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.