Adaptation of internal motor copy circuits in recovery after spinal cord injury.

脊髓损伤后恢复中内部运动复制电路的适应。

• 批准号: 10665596
• 负责人: George M Smith
• 金额: $ 54.34万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665596
• 关键词: Ablation; Affect; Animals; Automobile Driving; Autonomic Dysfunction; Axon; Back; Behavior; Brain Stem; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Cervical; Cervical spinal cord injury; Chest; Compensation; Conscious; Corticospinal Tracts; Data; Digit structure; Dorsal; Efferent Pathways; Food; Forelimb; Genetic; Goals; Hand; Human; Injury; Instruction; Lateral; Lesion; Life Style; Limb structure; Locomotion; Maps; Mediating; Memory; Motor; Motor Cortex; Motor Neurons; Movement; Muscle; Neurons; Pathway interactions; Patients; Pattern; Population; Rattus; Recovery; Recovery Support; Recovery of Function; Red nucleus structure; Rehabilitation therapy; Reticular Formation; Retrieval; Role; Sensory; Severities; Signal Transduction; Spinal Cord; Spinal cord injury; Structure of rubrospinal tract; Study models; System; Tactile; Time; Tracer; Training; Training Support; Unconscious State; dorsal column; grasp; improved; injury recovery; motor control; motor learning; motor skill learning; preservation; sensory feedback; skills; success

Abstract: Spinal cord injuries (SCI) affect approximately 100,000 patients each year and causes motor, sensory and autonomic dysfunction. Approximately 55% of all SCIs occur at the cervical level in human patients that effect forelimb. Patients effected by a cervical SCI desire recovery of hand and digit function to improve their current lifestyle. However, the majority of spinal cord injury models study the functional recovery associates with locomotion after thoracic lesions and not skilled forelimb patterning after cervical injuries. In general, skilled forelimb patterning is mediated through the corticospinal tract with support from indirect brainstem regions. Lesions that cut the corticospinal tract show significant loss of forelimb patterning; however, when the indirect pathways are preserved, rehabilitative training supports the recovery of the lost function. We show that this recovery is mediated by C3-C4 propriospinal neurons, a unique propriospinal neuron normally involved in the formation of an internal motor copy to correct movement errors during the movement. In this pathway, error correction is mediated by C3-C4 PN axons terminating onto neurons in the lateral reticular nucleus, a pre-cerebellar nucleus. Information is then routed through the cerebellum where the motor plan is compared to proprioceptive sensory information from the forelimb and back to brainstem motor control regions for execution. We hypothesize that after cervical injury this pathway undergoes rehabilitative adaptation to compensate for loss of the CST. Here we will take a systems approach to interrogate three components required for error correction and adaptation of this pathway. The first aim will examine the integration of information from several forelimb control pathways into the LRN and if modulation of LRN neuronal activity during rehabilitation augments recovery. The second aim will investigate the role of unconscious proprioceptive sensory information in rehabilitative recovery of injury. The third aim, will investigate the cerebellar efferent pathways connecting to know reticular regions involved in forelimb movements to determine their importance in driving recovery and error correction after cervical injury and during rehabilitation. Ultimately, this study will provide essential data to identify the pathways involved in rehabilitative recovery of skilled forelimb patterning after spinal cord injury and if recovery can be enhanced by activity dependent modulation during rehabilitative training.

抽象的： 脊髓损伤（SCI）每年影响约100,000名患者，并导致运动， 感觉和自主功能障碍。所有SCI的大约55％发生在宫颈水平 影响前肢的人类患者。通过宫颈SCI渴望恢复的患者 和数字功能以改善他们当前的生活方式。但是，大多数脊髓损伤 模型研究了胸腔病变后与运动的功能恢复相关联合 颈椎损伤后熟练的前肢图案。通常，熟练的前肢图案是 通过间接脑干区域的支撑，通过皮质脊髓道介导。病变 切割皮质脊髓束显示前肢图案的显着丧失。但是，当 保留间接途径，康复训练支持丢失功能的恢复。 我们表明，这种恢复是由C3-C4普遍性神经元介导的，这是一种独特的前脊髓神经元 神经元通常参与内部电机副本的形成以纠正运动错误 在运动期间。在此途径中，误差校正是由C3-C4 PN轴突介导的 终止于侧向核的神经元，一种前脑核。信息是 然后穿过小脑，在该小脑中，将电动机计划与本体感受相提并论 从前肢到脑干电机控制区域的信息进行执行。我们 假设宫颈损伤后这种途径经历了康复适应 补偿CST的损失。在这里，我们将采用系统方法来询问三个 该路径的误差校正和适应所需的组件。第一个目标 检查从几个前肢控制途径中的信息集成到LRN，然后 如果在康复过程中调节LRN神经元活性会增加恢复。第二个目标 将研究无意识的本体感受感官信息在康复中的作用 恢复伤害。第三个目标将调查连接到 知道前肢运动涉及的网状区域以确定其在驾驶中的重要性 宫颈损伤和康复期间的恢复和误差校正。最终，这项研究 将提供必要的数据，以确定培养技术恢复的途径 脊髓损伤后的前肢图案，如果可以通过活动来增强恢复 康复培训期间的依赖调制。

项目成果

Chemogenetic modulation of sensory afferents induces locomotor changes and plasticity after spinal cord injury.

• DOI: 10.3389/fnmol.2022.872634
• 发表时间: 2022
• 期刊: FRONTIERS IN MOLECULAR NEUROSCIENCE
• 影响因子: 4.8
• 作者: Eisdorfer, Jaclyn T.;Sobotka-Briner, Hannah;Schramfield, Susan;Moukarzel, George;Chen, Jie;Campion, Thomas J.;Smit, Rupert;Rauscher, Bradley C.;Lemay, Michel A.;Smith, George M.;Spence, Andrew J.
• 通讯作者: Spence, Andrew J.

Altered Amniotic Fluid Levels of Hyaluronic Acid in Fetal Rats with Myelomeningocele: Understanding Spinal Cord Injury.

脊髓脊膜膨出胎鼠羊水透明质酸水平的改变：了解脊髓损伤。

• DOI: 10.1089/neu.2018.5894
• 发表时间: 2019
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: Zieba,Jolanta;Walczak,Maciej;Gordiienko,Oleg;Gerstenhaber,JonathanA;Smith,GeorgeM;Krynska,Barbara
• 通讯作者: Krynska,Barbara