Enjin Anders, Perry Sharn, Hilscher Markus M, Nagaraja Chetan, Larhammar Martin, Gezelius Henrik, Eriksson Anders, Leão Katarina E, Kullander Klas
Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden.
Department of Neuroscience, Uppsala University, 751 24 Uppsala, Sweden
J Neurosci. 2017 Jun 7;37(23):5634-5647. doi: 10.1523/JNEUROSCI.0949-16.2017. Epub 2017 May 8.
When activating muscles, motor neurons in the spinal cord also activate Renshaw cells, which provide recurrent inhibitory feedback to the motor neurons. The tight coupling with motor neurons suggests that Renshaw cells have an integral role in movement, a role that is yet to be elucidated. Here we used the selective expression of the nicotinic cholinergic receptor α2 () in mice to genetically target the vesicular inhibitory amino acid transporter (VIAAT) in Renshaw cells. Loss of VIAAT from -expressing Renshaw cells did not impact any aspect of drug-induced fictive locomotion in the neonatal mouse or change gait, motor coordination, or grip strength in adult mice of both sexes. However, motor neurons from neonatal mice lacking VIAAT in Renshaw cells received spontaneous inhibitory synaptic input with a reduced frequency, showed lower input resistance, and had an increased number of proprioceptive glutamatergic and calbindin-labeled putative Renshaw cell synapses on their soma and proximal dendrites. Concomitantly, Renshaw cells developed with increased excitability and a normal number of cholinergic motor neuron synapses, indicating a compensatory mechanism within the recurrent inhibitory feedback circuit. Our data suggest an integral role for Renshaw cell signaling in shaping the excitability and synaptic input to motor neurons. We here provide a deeper understanding of spinal cord circuit formation and the repercussions for the possible role for Renshaw cells in speed and force control. Our results suggest that while Renshaw cells are not directly required as an integral part of the locomotor coordination machinery, the development of their electrophysiological character is dependent on vesicular inhibitory amino acid transporter-mediated signaling. Further, Renshaw cell signaling is closely associated with the molding of motor neuron character proposing the existence of a concerted maturation process, which seems to endow this particular spinal cord circuit with the plasticity to compensate for loss of the Renshaw cell in adult circuit function.
在激活肌肉时，脊髓中的运动神经元也会激活闰绍细胞，闰绍细胞会向运动神经元提供回返性抑制性反馈。与运动神经元的紧密耦合表明闰绍细胞在运动中具有不可或缺的作用，而这一作用尚待阐明。在此，我们利用烟碱型胆碱能受体α2（ ）在小鼠中的选择性表达，对闰绍细胞中的囊泡抑制性氨基酸转运体（VIAAT）进行基因靶向操作。从表达 的闰绍细胞中缺失VIAAT，对新生小鼠药物诱导的虚拟运动的任何方面均无影响，也未改变成年雌雄小鼠的步态、运动协调性或握力。然而，闰绍细胞中缺乏VIAAT的新生小鼠的运动神经元接受的自发抑制性突触输入频率降低，输入电阻较低，并且在其胞体和近端树突上，本体感觉性谷氨酸能和钙结合蛋白标记的假定闰绍细胞突触数量增加。与此同时，闰绍细胞兴奋性增强，胆碱能运动神经元突触数量正常，这表明在回返性抑制反馈回路中存在一种补偿机制。我们的数据表明闰绍细胞信号在塑造运动神经元的兴奋性和突触输入方面具有不可或缺的作用。我们在此对脊髓回路形成以及闰绍细胞在速度和力量控制中可能发挥的作用所产生的影响有了更深入的理解。我们的结果表明，虽然闰绍细胞并非运动协调机制不可或缺的直接组成部分，但其电生理特性的发育依赖于囊泡抑制性氨基酸转运体介导的信号传导。此外，闰绍细胞信号与运动神经元特性的塑造密切相关，这表明存在一个协同成熟过程，该过程似乎赋予了这个特定的脊髓回路可塑性，以补偿成年回路功能中闰绍细胞的缺失。
