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Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits

journal contribution
posted on 2023-05-20, 01:57 authored by Sharn PerrySharn Perry, Larhammar, M, Viellard, J, Nagaraja, C, Hilscher, MM, Tafreshiha, A, Rofo, F, Caixeta, FV, Kullander, K
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.

History

Publication title

Journal of Neuroscience

Volume

39

Issue

10

Pagination

1771-1782

ISSN

0270-6474

Department/School

Wicking Dementia Research Education Centre

Publisher

Soc Neuroscience

Place of publication

11 Dupont Circle, Nw, Ste 500, Washington, USA, Dc, 20036

Rights statement

Copyright 2019 The Authors

Repository Status

  • Restricted

Socio-economic Objectives

Other health not elsewhere classified

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