Lanuza Guillermo M, Gosgnach Simon, Pierani Alessandra, Jessell Thomas M, Goulding Martyn
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuron. 2004 May 13;42(3):375-86. doi: 10.1016/s0896-6273(04)00249-1.
The sequential stepping of left and right limbs is a fundamental motor behavior that underlies walking movements. This relatively simple locomotor behavior is generated by the rhythmic activity of motor neurons under the control of spinal neural networks known as central pattern generators (CPGs) that comprise multiple interneuron cell types. Little, however, is known about the identity and contribution of defined interneuronal populations to mammalian locomotor behaviors. We show a discrete subset of commissural spinal interneurons, whose fate is controlled by the activity of the homeobox gene Dbx1, has a critical role in controlling the left-right alternation of motor neurons innervating hindlimb muscles. Dbx1 mutant mice lacking these ventral interneurons exhibit an increased incidence of cobursting between left and right flexor/extensor motor neurons during drug-induced locomotion. Together, these findings identify Dbx1-dependent interneurons as key components of the spinal locomotor circuits that control stepping movements in mammals.
左右肢体的顺序性迈步是行走运动的一种基本运动行为。这种相对简单的运动行为是由运动神经元的节律性活动产生的，该活动受脊髓神经网络（称为中枢模式发生器，即CPG）的控制，CPG由多种中间神经元细胞类型组成。然而，关于特定中间神经元群体对哺乳动物运动行为的特性和贡献，我们所知甚少。我们发现，连合脊髓中间神经元的一个离散亚群，其命运受同源框基因Dbx1活性的控制，在控制支配后肢肌肉的运动神经元的左右交替方面起着关键作用。缺乏这些腹侧中间神经元的Dbx1突变小鼠在药物诱导的运动过程中，左右屈肌/伸肌运动神经元之间的共发放频率增加。这些发现共同表明，依赖Dbx1的中间神经元是控制哺乳动物迈步运动的脊髓运动回路的关键组成部分。
