Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

Sci Rep. 2017 Jan 27:7:41369. doi: 10.1038/srep41369.

Abstract

Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evoked Potentials
  • Gene Silencing
  • Glutamates / metabolism
  • Homeodomain Proteins / metabolism*
  • Integrases / metabolism*
  • Interneurons / metabolism*
  • Lumbar Vertebrae / metabolism
  • Mice
  • Mice, Transgenic
  • Motor Activity / physiology*
  • Motor Neurons / metabolism
  • Spinal Cord / metabolism*
  • Synapses / metabolism
  • Synaptic Transmission
  • Transcription Factors / metabolism*
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Glutamates
  • Homeodomain Proteins
  • Shox2 protein, mouse
  • Slc17a6 protein, mouse
  • Transcription Factors
  • Vesicular Glutamate Transport Protein 2
  • Hb9 protein, mouse
  • Cre recombinase
  • Integrases