title: Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.
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/Δmice 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.
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Caldeira
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.|Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, US.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Dougherty
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Borgius
authors.affiliation: Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Ole
authors.initials: O
authors.lastname: Kiehn
mesh_terms: D000818:Animals; D005071:Evoked Potentials; D020868:Gene Silencing; D005971:Glutamates / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009046:Motor Neurons / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D005971:Glutamates; D018398:Homeodomain Proteins; C484663:Shox2 protein, mouse; C493477:Slc17a6 protein, mouse; D014157:Transcription Factors; D050599:Vesicular Glutamate Transport Protein 2; C084059:Hb9 protein, mouse; C045073:Cre recombinase; D019426:Integrases