Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity

  1. Juliette Boeri
  2. Claude Meunier
  3. Hervé Le Corronc
  4. Pascal Branchereau
  5. Yulia Timofeeva
  6. François-Xavier Lejeune
  7. Christine Mouffle
  8. Hervé Arulkandarajah
  9. Jean Marie Mangin
  10. Pascal Legendre  Is a corresponding author
  11. Antonny Czarnecki  Is a corresponding author
  1. Sorbonne University, France
  2. Université de Paris, France
  3. Université de Bordeaux, CNRS, France
  4. UCL Queen Square Institute of Neurology, University College London, United Kingdom
  5. Institut du Cerveau et de la Moelle Épinière, France
  6. Université Pierre et Marie Curie, France

Abstract

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.

Data availability

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).

Article and author information

Author details

  1. Juliette Boeri

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Claude Meunier

    Centre de Neurosciences Intégratives et Cognition, CNRS UMR 8002, Institut Neurosciences et Cognition, Université de Paris, PARIS, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Hervé Le Corronc

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Pascal Branchereau

    Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA) - UMR 5287, Université de Bordeaux, CNRS, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3972-8229
  5. Yulia Timofeeva

    Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, LONDON, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. François-Xavier Lejeune

    U1127 INSERM, Institut du Cerveau et de la Moelle Épinière, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Christine Mouffle

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Hervé Arulkandarajah

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Jean Marie Mangin

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Pascal Legendre

    INSERM, UMR_S 1130, CNRS, UMR 8246, Neuroscience Paris Seine, Institute of Biology Paris Seine, Sorbonne University, Paris, France
    For correspondence
    pascal.legendre@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5086-4515
  11. Antonny Czarnecki

    Neurosciences Paris Seine (UM119 UPMC, UMR8246 CNRS, U1130 INSERM), Université Pierre et Marie Curie, Paris, France
    For correspondence
    antonny.czarnecki@u-bordeaux.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5104-034X

Funding

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.

Ethics

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.

Reviewing Editor

  1. Jeffrey C Smith, National Institute of Neurological Disorders and Stroke, United States

Publication history

  1. Received: August 31, 2020
  2. Accepted: April 24, 2021
  3. Accepted Manuscript published: April 26, 2021 (version 1)
  4. Accepted Manuscript updated: April 29, 2021 (version 2)
  5. Version of Record published: May 21, 2021 (version 3)

Copyright

© 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.

Metrics

  • 637
    Page views
  • 115
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Juliette Boeri
  2. Claude Meunier
  3. Hervé Le Corronc
  4. Pascal Branchereau
  5. Yulia Timofeeva
  6. François-Xavier Lejeune
  7. Christine Mouffle
  8. Hervé Arulkandarajah
  9. Jean Marie Mangin
  10. Pascal Legendre
  11. Antonny Czarnecki
(2021)
Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity
eLife 10:e62639.
https://doi.org/10.7554/eLife.62639

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Carolyn Elya, Danylo Lavrentovich ... Benjamin de Bivort
    Research Article Updated

    For at least two centuries, scientists have been enthralled by the “zombie” behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the Entomophthora muscae-Drosophila melanogaster “zombie fly” system to reveal the mechanistic underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a high-throughput approach to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), the latter being solely responsible for juvenile hormone (JH) synthesis and release. Using a machine learning classifier to identify summiting animals in real time, we observed that PI-CA neurons and CA appeared intact in summiting animals, despite invasion of adjacent regions of the “zombie fly” brain by E. muscae cells and extensive host tissue damage in the body cavity. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly’s hemolymph, activating a neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.

    1. Neuroscience
    Flavia Venetucci Gouveia, Jurgen Germann ... Clement Hamani
    Research Article Updated

    Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas – together with patient age – were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.