Multielectrode recording in spinal cord during locomotion and rehabilitation afte

描述（由申请人提供）：我们的目标是从大鼠脊髓横断下的脊髓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。 这些数据将是独特的和新颖的，对我们理解脊髓损伤有重大的潜在影响，并可能将技术转移到临床应用。 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，以实现我们的目标。 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，其记录位点沿着其长度，使用新型编织复合电极。 我们将增加记录点分布沿着插入探针长度，以采样跨层神经活动。 为此，我们将在现有结构中添加激光消融技术。 我们还计划将组件导线直径减少2-3倍（从目前的13微米导线加上绝缘组件），将导线和探头的顺应性提高16至81倍，超过目前的值。 具体目标二：我们将使用我们的电极记录在T9/10脊髓（ST）大鼠（新生和成年ST大鼠损伤）的机器人辅助康复过程中脊髓的活动模式。 我们假设SCI后的机器人康复会导致神经活动的动态变化，这种变化每天都在持续，并与改善功能恢复和体重支持相关。 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措施。 具体目标3：我们将在T9/10脊髓大鼠（新生和成年ST大鼠损伤）中进行椎管内微刺激测试，无论是在机器人辅助康复过程中还是之后。 我们的假设是，在训练的早期和后期，各组之间的微刺激差异将与功能恢复和机器人训练效果相关。 这些新的刺激数据也有望提供一套新的结果措施和电路测试工具，用于评估局灶性脊髓刺激，康复和神经可塑性的相互作用。 这个项目有可能对我们使用标准动物模型理解脊髓功能，损伤和康复过程产生巨大的，可能是变革性的影响。 此外，目标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，从而实现新一代的神经记录工具和神经修复术。 公共卫生相关性：该项目改进了可用于基础科学和临床应用的新电极，并将其用于以前从未进行过的康复过程中的脊髓记录。 所获得的信息可能有助于设计更好的脊髓损伤康复和治疗方法，并有助于了解疾病进展。 所开发的电极可能具有超出本项目的许多基础和临床应用。

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.