title: Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons.
abstract: Locomotion is controlled by spinal networks that generate rhythm and coordinate left-right and flexor-extensor patterning. Defined populations of spinal interneurons have been linked to patterning circuits; however, neurons comprising the rhythm-generating kernel have remained elusive. Here, we identify an ipsilaterally projecting excitatory interneuron population, marked by the expression of Shox2 that overlaps partially with V2a interneurons. Optogenetic silencing or blocking synaptic output of Shox2 interneurons (INs) in transgenic mice perturbed rhythm without an effect on pattern generation, whereas ablation of the Shox2 IN subset coinciding with the V2a population was without effect. Most Shox2 INs are rhythmically active during locomotion and analysis of synaptic connectivity showed that Shox2 INs contact other Shox2 INs, commissural neurons, and motor neurons, with preference for flexor motor neurons. Our findings focus attention on a subset of Shox2 INs that appear to participate in the rhythm-generating kernel for spinal locomotion.
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Dougherty
authors.forename: Laskaro
authors.initials: L
authors.lastname: Zagoraiou
authors.forename: Daisuke
authors.initials: D
authors.lastname: Satoh
authors.forename: Ismini
authors.initials: I
authors.lastname: Rozani
authors.forename: Staceyann
authors.initials: S
authors.lastname: Doobar
authors.forename: Silvia
authors.initials: S
authors.lastname: Arber
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.forename: Ole
authors.initials: O
authors.lastname: Kiehn
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D055724:Electrophysiological Phenomena; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D020868:Gene Silencing; D018698:Glutamic Acid / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D062308:Optogenetics; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018398:Homeodomain Proteins; C484663:Shox2 protein, mouse; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D012701:Serotonin; D018698:Glutamic Acid; D016202:N-Methylaspartate