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Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. Univ Tasmania, Wicking Dementia Res & Educ Ctr, Hobart, Tas 7000, Australia.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. Denali Therapeut, San Francisco, CA 94080 USA.ORCID iD: 0000-0002-1547-6760
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.ORCID iD: 0000-0001-9768-9462
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2019 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 10, p. 1771-1782Article in journal (Refereed) Published
Abstract [en]

Neuronal networks within the spinal cord, collectively known as the central pattern generator (CPG), coordinate rhythmic movements underlying locomotion. The transcription factor doublesex and mab-3-related transcription factor 3 (DMRT3) is involved in the differentiation of the dorsal interneuron 6 class of spinal cord interneurons. In horses, a non-sense mutation in the Dmrt3 gene has major effects on gaiting ability, whereas mice lacking the Dmrt3 gene display impaired locomotor activity. Although the Dmrt3 gene is necessary for normal spinal network formation and function in mice, a direct role for Dmrt3-derived neurons in locomotor-related activities has not been demonstrated. Here we present the characteristics of the Dmrt3-derived spinal cord interneurons. Using transgenic mice of both sexes, we characterized interneurons labeled by their expression of Cre driven by the endogenous Dmrt3 promoter. We used molecular, retrograde tracing and electrophysiological techniques to examine the anatomical, morphological, and electrical properties of the Dmrt3-Cre neurons. We demonstrate that inhibitory Dmrt3-Cre neurons receive extensive synaptic inputs, innervate surrounding CPG neurons, intrinsically regulate CPG neuron's electrical activity, and are rhythmically active during fictive locomotion, bursting at frequencies independent to the ventral root output. The present study provides novel insights on the character of spinal Dmrt3-derived neurons, data demonstrating that these neurons participate in locomotor coordination.

Place, publisher, year, edition, pages
SOC NEUROSCIENCE , 2019. Vol. 39, no 10, p. 1771-1782
Keywords [en]
central pattern generator, CPG, Dmrt3, interneuron, locomotion
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-379893DOI: 10.1523/JNEUROSCI.0326-18.2018ISI: 000460403400002PubMedID: 30578339OAI: oai:DiVA.org:uu-379893DiVA, id: diva2:1298593
Funder
The Swedish Brain FoundationThe Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved

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Perry, SharnLarhammar, MartinVieillard, JenniferNagaraja, ChetanHilscher, Markus MTafreshiha, AtiehKullander, Klas

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Perry, SharnLarhammar, MartinVieillard, JenniferNagaraja, ChetanHilscher, Markus MTafreshiha, AtiehRofo, FadiCaixeta, Fabio V.Kullander, Klas
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Developmental GeneticsDepartment of NeurosciencePhysiology
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