The effects of activity on propriospinal neuron morphology and connectivity

项目摘要。大多数人类脊髓损伤(SCI)在解剖学上是不完全的，可能 使可能传递信息通过损伤中心的固有脊髓通路完好无损。跟随SCI进入 啮齿动物，下行运动束萌发，越来越多地接触下行固有脊髓神经元(DPN)， 形成迂回电路，将信号传递到损伤的尾部。然而，还没有研究评估这种潜力。 在脊髓损伤后，上行PNS形成自下而上的绕行电路。我们之前发现沉默的时间很长 直接连接腰椎和颈椎膨大的上升三叉神经节(LAPN)中断 每条肢体腰带的协调性。令人惊讶的是，脊髓损伤后使这条解剖完整的通路沉默的情况有所改善。 运动功能。因此，评估LAPN的可塑性并确定这种可塑性可能如何是至关重要的 通过治疗干预来提炼。为此，将对LAPN的体细胞和树突形态进行表征 使用双病毒系统专门标记LAPN。我们还将使用高度安全的多病毒系统 修改狂犬病病毒以确定LAPN的直接突触输入来源。增加体力活动和 众所周知，康复训练可以改善脊髓损伤后的运动功能和解剖学结果。评估 体力活动和康复训练对脊髓损伤后LAPN可塑性和运动功能的影响 我们将通过将动物关在小笼子里或大笼子里来改变活动水平，以限制或促进活动。 大笼子里的动物也将接受康复训练，这模拟了临床康复。进一步 了解脊髓损伤诱导的神经可塑性，以及体力活动和康复训练如何影响这种可塑性 可塑性将进一步加深我们对脊髓损伤病理的理解，并提供新的治疗靶点。密切合作 在我的导师们的帮助下，我们制定了一项培训计划，将拓宽我的科学技能，促进独立 科学的思维，培养成为一名多产博士后所需的技能。肯塔基脊髓 损伤研究中心提供脊髓损伤及相关领域的临床和科学专业知识，并有 为学员当前和下一阶段的职业生涯做好准备。 假设。在脊髓损伤前，我们假设DPN、网状脊髓和感觉传入将为 LAPN。在脊髓损伤后，我们预计1)LAPN树枝晶取向改变，2)LAPN将被越来越多地联系 通过感觉传入形成自下而上的绕行回路；3)增加活动量，并在术后进行康复训练。 脊髓损伤可改善运动功能，影响树突重组，完善迂回回路。 目的1.鉴定LAPN的体细胞和树突形态，并确定其直接来源 突触传入LAPN。 目的2.评价活动和康复训练对运动功能、LAPN形态和功能的影响。 T10脊髓挫伤后LAPN的直接突触传入来源

Project Summary. The majority of human spinal cord injuries (SCI) are anatomically incomplete, potentially leaving propriospinal pathways, which may relay information past the injury epicenter, intact. Following SCI in rodents, descending motor tracts sprout and increasingly contact descending propriospinal neurons (DPNs), forming detour circuits to relay signals caudal to the injury. However, no studies have evaluated the potential for ascending PNs to form bottom-up detour circuits post-SCI. We previously found that silencing long ascending PNs (LAPNs), which directly connect the lumbar and cervical spinal enlargements, disrupted coordination at each limb girdle. Surprisingly, silencing this anatomically intact pathway post-SCI improved locomotor function. Thus, it is critical to evaluate LAPN plasticity, and determine how this plasticity might be refined by therapeutic interventions. To do so, LAPN somatic and dendritic morphology will be characterized using a dual-viral system to specifically label LAPNs. We will also use a multi-viral system with a highly modified rabies virus to identify the sources of direct synaptic input to LAPNs. Increased physical activity and rehabilitative training are known to improve locomotor function and anatomical outcomes post-SCI. To evaluate the impact of physical activity and rehabilitative training on LAPN plasticity and locomotor function post-SCI, we will alter activity levels by housing animals in tiny cages or in large cages to restrict or facilitate activity. Animals in large cages will also receive rehabilitative training, which mimics clinical rehabilitation. Further understanding SCI-induced neuroplasticity, and how physical activity and rehabilitative training impact this plasticity will further our understanding of SCI pathology and provide new therapeutic targets. Working closely with my mentors, we have developed a training plan that will broaden my scientific skills, facilitate independent scientific thought, and cultivate skills needed to be a productive postdoctoral fellow. The Kentucky Spinal Cord Injury Research Center provides clinical and scientific expertise in SCI and related fields, and has a history of successfully preparing trainees for current and next stages in their careers. Hypothesis. Pre-SCI we hypothesize that DPNs, reticulospinals, and sensory afferents will provide input to LAPNs. Post-SCI we anticipate 1) LAPN dendrite orientation change, 2) LAPNs will be increasingly contacted by sensory afferents to form bottom-up detour circuits, and 3) increased activity plus rehabilitative training post- SCI will improve locomotor function, impact dendrite reorganization, and refine detour circuits. Aim 1. Characterize the somatic and dendritic morphology of LAPNs, and identify the sources of direct synaptic input onto LAPNs. Aim 2. Evaluate the effects of activity and rehabilitative training on locomotor function, LAPN morphology, and the sources of direct synaptic inputs to LAPNs after T10 contusive spinal cord injury.