Multielectrode recording in spinal cord during locomotion and rehabilitation afte

描述（由申请人提供）：我们的目标是在大鼠脊髓横断下方获得稳定的多电极记录，并跟踪脊髓损伤后和康复过程中发生的神经变化。为此，我们将使用多电极神经记录和微刺激。这些数据将是独特和新颖的，对我们对脊髓损伤的理解有重大的潜在影响，并可能将技术转移到临床应用中。我们将使用并进一步开发在我们实验室发起的新型电极设计来实现我们的目标。具体目标1：我们将进一步开发一种慢性椎管内多电极探针，使用新型编织复合电极，沿其长度记录位点。我们将增加沿插入探针长度分布的记录位点，以便跨层取样神经活动。为了做到这一点，我们将在我们现有的建筑中添加激光消融技术。我们还计划将组件线直径减少2-3倍（从目前的13微米线加上绝缘组件），将导线和探头的合规性提高16到81倍，超出电流值。具体目标2：我们将使用我们的电极记录机器人辅助康复T9/10脊椎化（ST）大鼠（包括新生和成年ST大鼠损伤）整个过程中的脊髓活动模式。我们假设，脊髓损伤后的机器人康复会导致神经活动的动态改变，这种改变每天都在持续，并与功能恢复和体重支持的改善有关。这些实验将为脊柱水平的康复过程提供全新的数据和见解，并为评估康复和神经可塑性提供新的方法。具体目标3：我们将对T9/10脊椎大鼠（包括新生和成年ST大鼠损伤）进行脊柱内微刺激试验，无论是在机器人辅助康复的过程中还是之后。我们的假设是，在训练早期和后期，各组之间微刺激的差异将与功能恢复和机器人训练效果有关。这些新的刺激数据也有望为评估局灶性脊髓刺激、康复和神经可塑性的相互作用提供一套新的结果测量和电路测试工具。这个项目有潜力对我们理解脊髓功能、损伤和使用标准动物模型的康复过程产生巨大的、可能是革命性的影响。此外，Aim 1中调整的技术可能在许多大脑区域的神经记录和刺激中具有广泛的适用性，从而使新一代的神经记录工具和神经假肢成为可能。

DESCRIPTION (provided by applicant): Our goal is to obtain stable multielectrode recordings from spinal cord below a spinal transection in rats and follow the neural changes that occur after spinal cord injury and as a result of rehabilitation processes. To do this we will use multielectrode neural recordings and microstimulation. The data will be unique and novel with major potential impacts on our understanding of spinal cord injury, and possible technology transfer to clinical applications. We will use and further develop novel electrode designs initiated in our laboratory to achieve our objectives. Specific Aim 1 : We will further develop a chronic intraspinal multielectrode probe with recording sites along its length, using novel braided composite electrodes. We will add recording sites distributed along the inserted probe length in order to sample neural activity across laminae. To do this we will add laser ablation techniques to our existing construction. We also plan to reduce component wire diameter by a factor of 2-3 (from current 13 micron wire plus insulation components), increasing wire and probe compliance by a factor of 16 to 81 times beyond current values. Specific Aim 2: We will use our electrodes to record activity patterns in spinal cord throughout the process of robot assisted rehabilitation in T9/10 spinalized (ST) rats (both neonatal and adult ST rat injuries). We hypothesize that robot rehabilitation after SCI causes within session dynamic alterations in neural activity, which persist day to day, and correlate with improving functional recovery and weight support. These experiments will provide completely novel data and insights into the rehabilitation process at spinal levels and new measures for assessing rehabilitation and neuroplasticity. Specific Aim 3: We will perform intraspinal microstimulation tests in T9/10 spinalized rats (both neonatal and adult ST rat injuries), either throughout, or after, robot assisted rehabilitation. Our hypothesis is that differences in microstimulation between the groups early and late in training will correlate to functional recovery and robot training effects. These new stimulation data are also expected to provide a set of novel outcome measures and circuit test tools for assessing the interaction of focal spinal stimulation, rehabilitation and neuroplasticity. This project has the potential to have enormous and possibly transformative impacts on our understanding of spinal cord function, injury, and rehabilitation processes using standard animal models. Further, the technologies being tuned in Aim 1 may have broad applicability in neural recording and stimulation in many brain areas, and thus enable new generations of neural recording tools and neuroprosthetics. PUBLIC HEALTH RELEVANCE: This project makes improvements in new electrodes useful for basic scientific and clinical applications, and uses these for recordings from spinal cord during rehabilitation that have never been made before. The information gained may help design better rehabilitation and therapies for spinal cord injury and help understand disease progression. The electrodes developed may have numerous basic and clinical applications beyond this project.