Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity
Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the mouse spinal cord locomotor networks (E11.5-E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1R is the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in embryonic V1R and control their early developmental trajectory.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3 (Source data files for cluster analysis).
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Fondation pour la recherche medicale (DEQ20160334891)
- Pascal Legendre
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Experiments were performed in accordance with European Community guiding principles on the care and use of animals (86/609/CEE, CE Off J no. L358, 18 December 1986), French decree no. 97/748 of October 19, 1987 (Journal Officiel République Française, 20 October 1987, pp. 12245-12248). All procedures were carried out in accordance with the local ethics committee of local Universities and recommendations from the CNRS. pregnant mice were anesthetized by intramuscular injection of a mix of ketamine and xylazine and sacrificed using a lethal dose of CO2 after embryos of either sex were removed. Every effort was made to minimize suffering.
- Jeffrey C Smith, National Institute of Neurological Disorders and Stroke, United States
- Received: August 31, 2020
- Accepted: April 24, 2021
- Accepted Manuscript published: April 26, 2021 (version 1)
- Accepted Manuscript updated: April 29, 2021 (version 2)
- Version of Record published: May 21, 2021 (version 3)
© 2021, Boeri et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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