A new mechanistic and technological framework for uncovering the spinal cord neural systems important for functional recovery after injury

项目概要和摘要 增加脊髓损伤（SCI）后可塑性和再生的干预措施正在改善，但几乎没有改善。 我们知道哪些神经系统对这种干预最有效。基于感官 康复表明，皮肤和本体感觉神经元活动和运动神经元活动之间有很强的联系。 复苏先前的实验为脊髓（SC）的中间区（IZ）提供了强有力的支持， 一个重要的网站调解这一复苏。然而，很少有研究评估特定IZ神经元的作用， 在功能恢复方面。进展的关键障碍包括缺乏对细胞内特定细胞类型的表征。 IZ和缺乏工具来可视化电路并测试其在运动性能和恢复中的功能 SCI之后。我们的实验室将复杂的小鼠遗传方法与敏感的运动运动相结合 跟踪以了解SC如何编码感官信息以影响行为。使用此 方法，我们发现，中间区（IZ）小白蛋白阳性中间神经元（PV）是重要的， 触觉运动反应和运动。我们假设IZ-PV处理感觉信息以激活 运动过程中的特定肌肉群，它们在基于活动的功能恢复中发挥关键作用 SCI之后。识别对功能恢复重要的电路的能力取决于我们能多准确地 量化行为结果的差异。我们正在使用3D姿势实现无监督方法 动态和人工智能（AI）来表征敏感的行为生物标志物， 脊髓回路对恢复过程很重要。增加可塑性和再生的干预措施 正在改善，这个项目既确定了神经系统和突触机制，这将是最 有效地针对这些干预措施，并建立一个基于人工智能的平台， 啮齿类动物运动恢复的量化。因此，该项目为中国的发展做出了原创性的重要贡献。 脊髓研究领域的方式是专门与NINDS的中心任务对齐。此外，委员会认为， 我们在神经和行为水平上的实验研究为以下方面奠定了重要基础： 发展一个领先的研究项目，并获得研究脊髓的独立奖励资金 脊髓损伤后感觉运动功能和恢复的重要回路。为此，我制定了一个 一个全面和务实的职业发展计划，由一个强大的导师委员会支持， 实验室和部门级指导的业绩记录，以及SCI专项资助的杰出组合 美国国立卫生研究院，国防部和私人基金会的支持。我的职业发展活动将集中在四个方面 我的学术成就。1)辅导和指导侧重于实验室管理。（二） 我的独立研究计划和奖励资金的发展和增长，重点是SCI 基于研究差距的培训。3)明确机构职责，满足晋升要求 和任期4)扩大我的科学网络和个人资料。

Project Summary and Abstract Interventions that increase plasticity and regeneration after spinal cord injury (SCI) are improving, but little is known about the neural systems that would be most effective to target such interventions. Sensory based rehabilitation suggests a strong link between cutaneous and proprioceptive sensory neuron activity and motor recovery. Previous experiments provide strong support for the intermediate zone (IZ) of the spinal cord (SC) as an important site mediating this recovery. However, few studies have assessed the role of specific IZ neurons in functional recovery. Key barriers to progress include lack of characterization of specific cell types within the IZ and a paucity of tools to visualize circuits and test their functions in motor performance and recovery following SCI. Our lab combines sophisticated mouse genetic approaches with sensitive motor movement tracking to understand how sensory information is encoded by the SC to influence behavior. Using this approach, we uncovered that intermediate zone (IZ) parvalbumin positive interneurons (PVs) are important for tactile motor responses and locomotion. We hypothesize that IZ-PVs process sensory information to activate specific muscle groups during locomotion and that they play a critical role in activity-based functional recovery following SCI. The ability to identify circuits important for functional recovery relies on how accurately we can quantify differences in behavioral outcomes. We are implementing an unsupervised approach using 3-D pose dynamics and artificial intelligence (AI) to characterize both sensitive behavioral biomarkers and uncover key spinal cord circuits important for the recovery process. Interventions that increase plasticity and regeneration are improving, and this project both identifies the neural systems and synaptic mechanisms that would be most effective to target such interventions and establishes an AI-based platform for fast, reliable and unbiased quantification of motor recovery in rodents. Thus, this project makes original and important contributions to the field of spinal cord research in ways that are specifically aligned with central missions of the NINDS. Moreover, our experimental scrutiny at both the neural and behavioral levels establishes a critical foundation for developing a leading research program and securing independent award funding studying the spinal cord circuits important for sensorimotor function and recovery following SCI. To this end, I have developed a thorough and pragmatic career development plan supported by a strong committee of mentors with extensive track records of laboratory and departmental level mentoring and distinguished portfolios of SCI-specific grant support from the NIH, DoD and private foundations. My career development activities will be focused on four aspects of my academic success. 1) Mentorship and guidance focused on laboratory management. 2) Development and growth of my independent research program and award funding, with a focus on SCI research gap-based training. 3) Navigating institutional responsibilities and fulfilling requirements for promotion and tenure. 4) Expanding my scientific network and profile.