iScience paper

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. After spinal cord injury (SCI) rehabilitation is thought to mediate re-organization and plasticity of these spared supraspinal-propriospinal circuits leading to recovery of function. Which of these circuits is instrumental in promoting recovery of skilled forelimb patterning remains unclear. Here we investigated the involvement of cervical propriospinal interneurons (PNs) and rubrospinal neurons (RNs) in recovery of reaching and grasping behavior in rats after bilateral lesions of the corticospinal tract and dorsal columns at C5. These lesions result is a 50% loss in pellet retrieval scores that recovers to normal levels over a 4-weeks period of training. To reversibly silence these pathways, we used a tetracycline-inducible promoter to drive expression of hM4Di to identify CNO off-target effects when not expressed. Prior to lesioning the expression of hM4Di and addition of CNO showed no effect on pellet retrieval. After recovery from injury, silencing PNs caused a significant loss in single pellet retrieve success, with silencing of RNs playing a similar role; however, silencing both led to significantly greater loss. The data is of single pellet reaching studies after rehabilitation and functional recovery of successful reaching and grasping. Reaching success %, reaching attempts, and reaching scores are provided.

熟练前肢模式的形成受皮质脊髓束介导，并得到间接脑干区域的辅助。切断皮质脊髓束的损伤会导致前肢模式显著丧失；然而，当间接通路得以保留时，康复训练有助于恢复丧失的功能。脊髓损伤（SCI）后的康复被认为可以调节这些保留的皮层- propriospinal回路重组与可塑性，从而促进功能的恢复。在哪些回路中起关键作用以促进熟练前肢模式的恢复尚不明确。在本研究中，我们探讨了在C5处的皮质脊髓束和背柱的双侧损伤后，颈椎 propriospinal 内部神经元（PNs）和 rubrospinal 神经元（RNs）在恢复大鼠伸手和抓握行为中的作用。这些损伤导致50%的丸状物检索评分下降，经过4周的训练后恢复至正常水平。为了可逆地沉默这些通路，我们使用四环素诱导的启动子驱动hM4Di的表达，以识别CNO的非靶标效应。在损伤前，hM4Di的表达和CNO的添加对丸状物检索没有影响。从损伤中恢复后，沉默PNs导致单丸检索成功率显著下降，而沉默RNs也发挥了类似的作用；然而，同时沉默两者导致了更显著的损失。数据来自康复后和功能恢复成功的伸手和抓握的单丸伸手研究。提供了伸手成功率百分比、伸手尝试次数和伸手评分。