Diversity Supplement to 2R01NS064004

反射亢进是孤立性损害皮质脊髓束(CST)的破坏性后果。 起源于皮质，或在脊髓损伤(SCI)后。反射亢进有多种可能的机制。一 机制反映了CST丢失后损伤尾部本体感觉传入纤维的异常发芽； 更多的PA纤维在运动神经元上突触，PA反射的强度可能会增强。PA端子通常 在GABA能突触前抑制性调节下。我们假设，PA在受伤后萌发时没有 相关的GABA能突触前调节，这可以增强反射动作，导致临床 反射亢进的后果是痉挛和痉挛。 父母R01的总体重点是确定脊髓挫伤后哪些运动障碍可能是 可归因于CST丢失，然后启动CST修复以针对特定损害。建议数 《多样性补充》中的研究将检验单侧锥体束的GABA能失调假说。 损伤(PTX)，一种模型损伤，切断一个半球的所有CST轴突，而不会对脊髓造成损伤。 或颈髓挫伤，这是一种临床前损伤模型，损害了CST以及其他通路 脊髓的组成部分。我们将对脊髓中PA突触的变化进行高分辨率的形态分析 灰质(目标1)和一种新的多通道脊髓电生理记录方法(目标2) 解决反射亢进症。 该项目第一年的大部分时间将重点放在选择性CST损伤(PTX)后的反射亢进上。使用这个 Thelma补充项目的CST损伤模型通过提供额外的新颖功能来补充父R01脊髓损伤焦点 反射亢进问题的机制基础以及神经调节如何改善它。在附近 完成项目第一年后，候选人计划提交NRSA F31申请。成功完成 建议的第1年研究将使候选人能够准备具有竞争力的NRSA F31应用程序， 有影响力的发现的前提。预计在提交申请后将对脊髓损伤模型进行审查， 在第二年，该项目的成功完成将使人们了解反射亢进的机制。 除了进行研究外，候选人还将学习新的尖端技术，这些技术提供了一种新颖的 以及对反射亢进问题的独特看法，这将支持她与生理过程相关的训练 创伤后神经元兴奋性的潜在变化。 1

Hyperreflexia is a devastating consequence of a lesion that damages the corticospinal tract (CST), in isolation, or at its origins in the cortex, or after a spinal cord injury (SCI). Multiple possible mechanisms underlie hyperreflexia. One mechanism reflects aberrant sprouting of proprioceptive afferent (PA) fibers caudal to the injury after CST loss; with more PA fibers synapsing on motoneurons, the strength of PA reflexes may be augmented. PA terminals are normally under GABAergic presynaptic inhibitory regulation. We hypothesize that PA sprouting after an injury occurs without associated GABAergic presynaptic regulation and that this can enhance reflex actions, leading to the clinical consequences of hyperreflexia, which is spasticity and spasms. An overall focus of the parent R01 is to determine which motor impairments after a contusion SCI may be attributable to the loss of the CST, and then to initiate CST repair to target the particular impairment. The proposed studies in this Diversity Supplement will examine the GABAergic dysregulation hypothesis in a unilateral pyramidal tract lesion (PTX), a model injury that severs all CST axons from one hemisphere without producing injury to the spinal cord, or a cervical spinal cord contusion, a preclinical injury model that lesions the CST as well as other pathways and components of the spinal cord. We will use high-resolution morphologic analyses of PA synapse changes in the spinal gray matter (Aim 1) together with a novel multi-channel spinal cord electrophysiological recording approach (Aim 2) to address hyperreflexia. The focus for most of year 1 of the project will be on hyperreflexia after selective CST lesion (PTX). Using this CST lesion model for Thelma's supplement project complements the parent R01 SCI focus by providing additional novel mechanistic underpinnings of the problem of hyperreflexia and how neuromodulation can ameliorate it. Near the completion of year 1 of the project, the candidate plans to submit an NRSA F31 application. Successful completion of proposed year 1 studies will position the candidate to prepare a competitive NRSA F31 application based on a strong premise of impactful findings. It is expected that the SCI injury model will be examined after application submission, during year 2. Successful completion of the project will inform the mechanisms of hyperreflexia. In addition to conducting the research, the candidate will learn new cutting-edge techniques that provide a novel and unique perspective on the problem of hyperreflexia and this will bolster her training related to physiological processes underlying changes in neuronal excitability after trauma. 1