Tohyama Takamichi, Kinoshita Masaharu, Kobayashi Kenta, Isa Kaoru, Watanabe Dai, Kobayashi Kazuto, Liu Meigen, Isa Tadashi
Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
Department of Rehabilitation Medicine, Graduate School of Medicine, Keio University, Tokyo 160-8582, Japan.
Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):604-609. doi: 10.1073/pnas.1610787114. Epub 2017 Jan 3.
The direct cortico-motoneuronal connection is believed to be essential for the control of dexterous hand movements, such as precision grip in primates. It was reported, however, that even after lesion of the corticospinal tract (CST) at the C4-C5 segment, precision grip largely recovered within 1-3 mo, suggesting that the recovery depends on transmission through intercalated neurons rostral to the lesion, such as the propriospinal neurons (PNs) in the midcervical segments. To obtain direct evidence for the contribution of PNs to recovery after CST lesion, we applied a pathway-selective and reversible blocking method using double viral vectors to the PNs in six monkeys after CST lesions at C4-C5. In four monkeys that showed nearly full or partial recovery, transient blockade of PN transmission after recovery caused partial impairment of precision grip. In the other two monkeys, CST lesions were made under continuous blockade of PN transmission that outlasted the entire period of postoperative observation (3-4.5 mo). In these monkeys, precision grip recovery was not achieved. These results provide evidence for causal contribution of the PNs to recovery of hand dexterity after CST lesions; PN transmission is necessary for promoting the initial stage recovery; however, their contribution is only partial once the recovery is achieved.
直接的皮质-运动神经元连接被认为对于控制灵巧的手部运动至关重要，比如灵长类动物的精准抓握。然而，有报道称，即使在颈4-颈5节段的皮质脊髓束（CST）受损后，精准抓握在1-3个月内仍有很大程度的恢复，这表明恢复依赖于通过损伤部位上方的中间神经元的传导，比如颈中段的脊髓固有神经元（PNs）。为了获得脊髓固有神经元对皮质脊髓束损伤后恢复作用的直接证据，我们在6只猴子的颈4-颈5节段皮质脊髓束损伤后，使用双病毒载体对脊髓固有神经元应用了一种通路选择性和可逆性阻断方法。在4只显示出几乎完全或部分恢复的猴子中，恢复后脊髓固有神经元传导的短暂阻断导致了精准抓握的部分受损。在另外两只猴子中，在脊髓固有神经元传导的持续阻断下进行皮质脊髓束损伤，该阻断持续超过了术后观察的整个时期（3-4.5个月）。在这些猴子中，未实现精准抓握的恢复。这些结果为脊髓固有神经元对皮质脊髓束损伤后手灵巧性恢复的因果作用提供了证据；脊髓固有神经元传导对于促进恢复的初始阶段是必要的；然而，一旦实现恢复，它们的作用只是部分的。
