Functional and transcriptomic basis of enhanced muscle function after denervation-induced paralysis of the mouse whisker pad

The functional state of denervated muscle is a critical factor in the ability to restore movement after injury- or disease-related paralysis. Here we used peripheral optogenetic stimulation in the mouse whisker system to investigate the time course of changes in nerve and muscle function following facial nerve transection. While most skeletal muscles atrophy after lower motor neuron denervation, optogenetic muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after denervation. Transcriptome profiling showed distinct regulation of multiple gene families in denervated whisker pad muscles compared to the atrophy-prone soleus, including prominent changes in ion channels and contractile fibers. Together, our results define the functional and transcriptomic landscape of muscle denervation supersensensitivty, and have implications for restoring movement after neuromuscular injury or disease. RNA-seq of intact or lesioned skin and muscle from rostral whisker pad.

失神经支配肌肉（denervated muscle）的功能状态，是损伤或疾病引发瘫痪后运动功能恢复能力的关键影响因素。本研究借助小鼠触须系统的外周光遗传刺激（peripheral optogenetic stimulation），探究面神经切断（facial nerve transection）后神经与肌肉功能的动态变化进程。尽管多数骨骼肌在经历下运动神经元（lower motor neuron）失神经支配后会出现萎缩，但对瘫痪触须垫实施光遗传肌肉刺激后发现，自失神经支配48小时起，触须运动的灵敏度、速度与幅度持续升高，且易疲劳性显著降低。转录组分析（transcriptome profiling）结果显示，相较于易发生萎缩的比目鱼肌（soleus），失神经支配的触须垫肌肉中多个基因家族的表达调控存在显著差异，其中离子通道与收缩纤维的变化尤为突出。综上，本研究明确了肌肉失神经支配超敏感性的功能与转录组特征，可为神经肌肉损伤或疾病后的运动功能恢复提供理论支撑。本数据集包含吻侧触须垫完整或受损的皮肤与肌肉的RNA测序（RNA-seq）数据。