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.
- Ole Kiehn
- Ole Kiehn
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All surgical procedures and experimental manipulations were approved by the local ethical committee and the Swedish Animal Welfare Agency and included in the ethical permit N. 29/2014.
- Ronald L Calabrese, Emory University, United States
© 2017, Bellardita et al.
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