Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California.
Department of Biomedical Sciences, Margaret M. McCann, Creighton University, Omaha, Nebraska.
J Comp Neurol. 2020 Jun;528(8):1293-1306. doi: 10.1002/cne.24826. Epub 2019 Dec 9.
The corticospinal tract (CST) is the major descending pathway controlling voluntary hand function in primates, and though less dominant, it mediates voluntary paw movements in rats. As with primates, the CST in rats originates from multiple (albeit fewer) cortical sites, and functionally different motor and somatosensory subcomponents terminate in different regions of the spinal gray matter. We recently reported in monkeys that following a combined cervical dorsal root/dorsal column lesion (DRL/DCL), both motor and S1 CSTs sprout well beyond their normal terminal range. The S1 CST sprouting response is particularly dramatic, indicating an important, if poorly understood, somatosensory role in the recovery process. As rats are used extensively to model spinal cord injury, we asked if the S1 CST response is conserved in rodents. Rats were divided into sham controls, and two groups surviving post-lesion for ~6 and 10 weeks. A DRL/DCL was made to partially deafferent one paw. Behavioral testing showed a post-lesion deficit and recovery over several weeks. Three weeks prior to ending the experiment, S1 cortex was mapped electrophysiologically, for tracer injection placement to determine S1 CST termination patterns within the cord. Synaptogenesis was also assessed for labeled S1 CST terminals within the dorsal horn. Our findings show that the affected S1 CST sprouts well beyond its normal range in response to a DRL/DCL, much as it does in macaque monkeys. This, along with evidence for increased synaptogenesis post-lesion, indicates that CST terminal sprouting following a central sensory lesion, is a robust and conserved response.
皮质脊髓束（CST）是控制灵长类动物手部自主运动的主要下行通路，尽管其作用较小，但它介导大鼠的手部自主运动。与灵长类动物一样，大鼠的 CST 起源于多个（尽管较少）皮质部位，功能不同的运动和躯体感觉亚成分终止于脊髓灰质的不同区域。我们最近在猴子中报告称，在联合颈椎背根/背柱损伤（DRL/DCL）后，运动和 S1 CST 均在其正常末端范围之外大量发芽。S1 CST 发芽反应特别显著，表明在恢复过程中存在着重要的、尽管尚未被充分理解的躯体感觉作用。由于大鼠被广泛用于脊髓损伤模型，我们询问 S1 CST 反应是否在啮齿动物中保守。大鼠分为假手术对照组和两组，分别在损伤后存活 6 周和 10 周。进行 DRL/DCL 以部分去传入一只爪子。行为测试显示损伤后数周的缺陷和恢复。在实验结束前 3 周，用电生理学方法对 S1 皮层进行映射，以便在脊髓内确定 S1 CST 终止模式进行示踪剂注射。还评估了背角内标记的 S1 CST 末端的突触形成。我们的研究结果表明，受影响的 S1 CST 在 DRL/DCL 刺激下会超出其正常范围发芽，就像在猕猴中一样。这与损伤后突触形成增加的证据一起表明，中枢感觉损伤后 CST 末端发芽是一种强大而保守的反应。
