Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex

  1. David Orduz
  2. Paloma P Maldonado
  3. Maddalena Balia
  4. Mateo Vélez-Fort
  5. Vincent de Sars
  6. Yuchio Yanagawa
  7. Valentina Emiliani
  8. Maria Cecilia Angulo  Is a corresponding author
  1. Institut national de la santé et de la recherche médicale, France
  2. The Royal Academy of Arts and Sciences, Netherlands
  3. National Institute for Medical Research, United Kingdom
  4. Université Paris Descartes, Sorbonne Paris Cité, France
  5. Gunma University Graduate School of Medicine, Japan

Abstract

NG2 cells, oligodendrocyte progenitors, receive a major synaptic input from interneurons in the developing neocortex. It is presumed that these precursors integrate cortical networks where they act as sensors of neuronal activity. We show that NG2 cells of the developing somatosensory cortex form a transient and structured synaptic network with interneurons that follows its own rules of connectivity. Fast-spiking interneurons, highly connected to NG2 cells, target proximal subcellular domains containing GABAA receptors with γ2 subunits. Conversely, non-fast-spiking interneurons, poorly connected with these progenitors, target distal sites lacking this subunit. In the network, interneuron-NG2 cell connectivity maps exhibit a local spatial arrangement reflecting innervation only by nearest interneurons. This microcircuit architecture shows a connectivity peak at PN10, coinciding with a switch to massive oligodendrocyte differentiation. Hence, GABAergic innervation of NG2 cells is temporally and spatially regulated from the subcellular to the network level in coordination with the onset of oligodendrogenesis.

Article and author information

Author details

  1. David Orduz

    INSERM U1128, Neurophysiology and New Microscopies Laboratory, Institut national de la santé et de la recherche médicale, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Paloma P Maldonado

    Netherlands Institute for Neuroscience, The Royal Academy of Arts and Sciences, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Maddalena Balia

    INSERM U1128, Neurophysiology and New Microscopies Laboratory, Institut national de la santé et de la recherche médicale, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Mateo Vélez-Fort

    Division of Neurophysiology, National Institute for Medical Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Vincent de Sars

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Yuchio Yanagawa

    Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Valentina Emiliani

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Maria Cecilia Angulo

    INSERM U1128, Neurophysiology and New Microscopies Laboratory, Institut national de la santé et de la recherche médicale, Paris, France
    For correspondence
    maria-cecilia.angulo@parisdescartes.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments followed European Union and institutional guidelines for the care and use of laboratory of the INSERM. All of the animals were handled according to approved institutional animal care and use protocols of the University Paris Descartes. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University Paris Descartes (Permit Number: CEEA34.MCA.070.12). Every effort was made to minimize suffering.

Copyright

© 2015, Orduz 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

  • 2,841
    views
  • 875
    downloads
  • 82
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

Share this article

https://doi.org/10.7554/eLife.06953

Further reading

    1. Neuroscience
    Jakob Rupert, Dragomir Milovanovic
    Insight

    By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.

    1. Neuroscience
    Brian C Ruyle, Sarah Masud ... Jose A Morón
    Research Article

    Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.