Ribotta M G, Provencher J, Feraboli-Lohnherr D, Rossignol S, Privat A, Orsal D
Institut National de la Santé et de la Recherche Médicale U336, Ecole Pratique des Hautes Etudes, Université Montpellier II, F-34095 Montpellier, France.
J Neurosci. 2000 Jul 1;20(13):5144-52. doi: 10.1523/JNEUROSCI.20-13-05144.2000.
Traumatic lesions of the spinal cord yield a loss of supraspinal control of voluntary locomotor activity, although the spinal cord contains the necessary circuitry to generate the basic locomotor pattern. In spinal rats, this network, known as central pattern generator (CPG), was shown to be sensitive to serotonergic pharmacological stimulation. In previous works we have shown that embryonic raphe cells transplanted into the sublesional cord of adult rats can reinnervate specific targets, restore the lesion-induced increase in receptor densities of neurotransmitters, promote hindlimb weight support, and trigger a locomotor activity on a treadmill without any other pharmacological treatment or training. With the aim of discriminating whether the action of serotonin on CPG is associated to a specific level of the cord, we have transplanted embryonic raphe cells at two different levels of the sublesional cord (T9 and T11) and then performed analysis of the kinematic and EMG activity synchronously recorded during locomotion. Locomotor performances were correlated to the reinnervated level of the cord and compared to that of intact and transected nontransplanted animals. The movements expressed by T11 transplanted animals correspond to a well defined locomotor pattern comparable to that of the intact animals. On the contrary, T9 transplanted animals developed limited and disorganized movements as those of nontransplanted animals. The correlation of the locomotor performances with the level of reinnervation of the spinal cord suggests that serotonergic reinnervation of the L1-L2 level constitutes a key element in the genesis of this locomotor rhythmic activity. This is the first in vivo demonstration that transplanted embryonic raphe cells reinnervating a specific level of the cord activate a locomotor behavior.
脊髓创伤性损伤会导致对自主运动活动的脊髓上控制丧失,尽管脊髓包含产生基本运动模式的必要神经回路。在脊髓损伤的大鼠中,这种被称为中枢模式发生器(CPG)的网络已被证明对血清素能药理刺激敏感。在先前的研究中,我们已经表明,移植到成年大鼠损伤部位以下脊髓的胚胎中缝细胞可以重新支配特定靶点,恢复损伤引起的神经递质受体密度增加,促进后肢负重,并在没有任何其他药物治疗或训练的情况下在跑步机上引发运动活动。为了区分血清素对CPG的作用是否与脊髓的特定水平相关,我们在损伤部位以下脊髓的两个不同水平(T9和T11)移植了胚胎中缝细胞,然后对运动过程中同步记录的运动学和肌电图活动进行了分析。运动表现与脊髓的重新支配水平相关,并与完整和横断未移植动物的运动表现进行了比较。T11移植动物表现出的运动对应于一种明确的运动模式,与完整动物的运动模式相当。相反,T9移植动物的运动发展有限且杂乱无章,与未移植动物的运动相似。运动表现与脊髓重新支配水平的相关性表明,L1-L2水平的血清素能重新支配是这种运动节律活动产生的关键因素。这是首次在体内证明,移植到脊髓特定水平的胚胎中缝细胞重新支配会激活运动行为。