Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons

Neuron. 2013 Nov 20;80(4):920-33. doi: 10.1016/j.neuron.2013.08.015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Dependovirus / genetics
  • Electrophysiological Phenomena
  • Excitatory Amino Acid Agonists / pharmacology
  • Gene Silencing
  • Glutamic Acid / physiology
  • Homeodomain Proteins / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Interneurons / physiology*
  • Locomotion / drug effects
  • Locomotion / physiology*
  • Male
  • Mice
  • Motor Neurons / physiology
  • N-Methylaspartate / pharmacology
  • Neural Pathways / physiology
  • Optogenetics
  • Serotonin / pharmacology
  • Spinal Cord / cytology
  • Spinal Cord / physiology
  • Vesicular Glutamate Transport Protein 2 / physiology


  • Excitatory Amino Acid Agonists
  • Homeodomain Proteins
  • Shox2 protein, mouse
  • Slc17a6 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • Serotonin
  • Glutamic Acid
  • N-Methylaspartate