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

揭示脊髓神经系统对损伤后功能恢复至关重要的新机制和技术框架

• 批准号: 10391487
• 负责人: Victoria Eugenia Guadalupe Abraira
• 金额: $ 24.52万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10391487
• 关键词: 3-Dimensional; Anatomy; Artificial Intelligence; Award; Behavior; Behavioral; Behavioral Assay; Biological Markers; Complex; Cutaneous; Data; Development Plans; Elements; Ensure; Foundations; Funding; Gait; Genetic; Goals; Grant; Growth and Development function; Injury; Interneurons; Intervention; Label; Laboratories; Leg; Link; Liquid substance; Locomotion; Mediating; Mentors; Mentorship; Mission; Modeling; Motor; Movement; Muscle; National Institute of Neurological Disorders and Stroke; Natural regeneration; Neurons; Output; Parvalbumins; Pattern; Performance; Play; Population; Positioning Attribute; Privatization; Probability; Process; Proprioceptor; Publishing; Records; Recovery; Recovery of Function; Rehabilitation therapy; Research; Rodent; Rogaine; Role; Secure; Sensorimotor functions; Sensory; Sensory Process; Shapes; Site; Spinal Cord; Spinal Cord Contusions; Spinal cord injury; Structure; Synapses; System; Tactile; Technology; Testing; Therapeutic Intervention; Three-Dimensional Imaging; Touch sensation; Training; United States National Institutes of Health; Volition; base; behavior influence; behavioral outcome; career development; cell type; defined contribution; experimental study; genetic approach; improved; injury recovery; insight; kinematics; motor behavior; motor recovery; mouse genetics; programs; relating to nervous system; response; success; synergism; tool

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.

项目摘要和摘要 增加脊髓损伤后可塑性和再生的干预措施正在改善，但几乎没有 知道最有效的针对此类干预措施的神经系统。基于感官 康复表明皮肤和本体感知性感觉神经元活动与运动之间有很强的联系 恢复。以前的实验为脊髓（SC）的中间区（IZ）提供了强有力的支持 一个重要的站点，调解了这种恢复。但是，很少有研究评估特定IZ神经元的作用 在功能恢复中。进步的关键障碍包括缺乏特定细胞类型的表征 IZ和少数工具可视化电路并测试其在运动性能和恢复中的功能 跟随科学。我们的实验室将复杂的小鼠遗传方法与敏感运动运动相结合 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）白蛋白阳性中间神经元（PVS）对 触觉电动机反应和运动。我们假设IZ-PVS处理感官信息以激活 运动期间特定的肌肉群，并且它们在基于活动的功能恢复中起着至关重要的作用 跟随科学。识别电路对功能恢复重要的能力取决于我们的准确程度 量化行为结果的差异。我们正在使用3D姿势实施无监督的方法 动态和人工智能（AI）表征敏感的行为生物标志物和发现钥匙 脊髓电路对于恢复过程很重要。增加可塑性和再生的干预措施 正在改善 有效针对此类干预措施，并建立一个基于AI的平台，以快速，可靠和公正 定量啮齿动物的运动恢复。因此，该项目为 脊髓研究的领域以与NIND的中央任务特别一致的方式。而且， 我们对神经和行为层面的实验审查为 制定领先的研究计划并确保研究脊髓的独立奖励资金 SCI后的感官功能和恢复重要的电路。为此，我已经开发了 彻底而务实的职业发展计划由强大的导师委员会支持 实验室和部门一级指导的记录和科学特定赠款的杰出投资组合 NIH，国防部和私人基金会的支持。我的职业发展活动将集中于四个 我的学术成功的各个方面。 1）指导和指导专注于实验室管理。 2） 我的独立研究计划和奖励的发展和成长，重点是SCI 基于研究差距的培训。 3）导航机构责任和满足晋升的要求 和任期。 4）扩展我的科学网络和个人资料。