title: Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice.
abstract: 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.
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bellardita
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Caggiano
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Roberto
authors.initials: R
authors.lastname: Leiras
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Caldeira
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuchs
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Julien
authors.initials: J
authors.lastname: Bouvier
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Löw
authors.affiliation: Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ole
authors.identifier: http://orcid.org/0000-0002-5954-469X
authors.initials: O
authors.lastname: Kiehn
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D013035:Spasm / Q000503:physiopathology*; D062211:Spatio-Temporal Analysis; D013119:Spinal Cord Injuries / Q000150:complications*
keywords: motor neurons; mouse; neuroscience; persistent neural activity; spasms; spinal cord injury; spinal interneurons; spinal transection