Bellardita Carmelo, Caggiano Vittorio, Leiras Roberto, Caldeira Vanessa, Fuchs Andrea, Bouvier Julien, Löw Peter, Kiehn Ole
Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Elife. 2017 Feb 13;6:e23011. doi: 10.7554/eLife.23011.
Spasms after spinal cord injury (SCI) are debilitating involuntary muscle contractions that have been associated with increased motor neuron excitability and decreased inhibition. However, whether spasms involve activation of premotor spinal excitatory neuronal circuits is unknown. Here we use mouse genetics, electrophysiology, imaging and optogenetics to directly target major classes of spinal interneurons as well as motor neurons during spasms in a mouse model of chronic SCI. We find that assemblies of excitatory spinal interneurons are recruited by sensory input into functional circuits to generate persistent neural activity, which interacts with both the graded expression of plateau potentials in motor neurons to generate spasms, and inhibitory interneurons to curtail them. Our study reveals hitherto unrecognized neuronal mechanisms for the generation of persistent neural activity under pathophysiological conditions, opening up new targets for treatment of muscle spasms after SCI.
脊髓损伤（SCI）后的痉挛是使人虚弱的非自主肌肉收缩，与运动神经元兴奋性增加和抑制作用减弱有关。然而，痉挛是否涉及脊髓前运动兴奋性神经元回路的激活尚不清楚。在这里，我们使用小鼠遗传学、电生理学、成像和光遗传学技术，在慢性脊髓损伤小鼠模型的痉挛过程中直接靶向脊髓中间神经元以及运动神经元的主要类别。我们发现，兴奋性脊髓中间神经元的集合通过感觉输入被募集到功能回路中，以产生持续的神经活动，这种活动与运动神经元中平台电位的分级表达相互作用以产生痉挛，并与抑制性中间神经元相互作用以抑制痉挛。我们的研究揭示了病理生理条件下产生持续神经活动的迄今未被认识的神经元机制，为治疗脊髓损伤后的肌肉痉挛开辟了新的靶点。
