1. Cell Biology
  2. Neuroscience
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Miro1-dependent mitochondrial dynamics in parvalbumin Interneurons

  1. Georgina Kontou
  2. Pantelis Antonoudiou
  3. Marina Podpolny
  4. Blanka R Szulc
  5. I Lorena Arancibia-Carcamo
  6. Nathalie F Higgs
  7. Guillermo Lopez-Domenech
  8. Patricia C Salinas
  9. Edward Mann
  10. Josef T Kittler  Is a corresponding author
  1. University College London, United Kingdom
  2. University of Oxford, United Kingdom
  3. UCL, United Kingdom
Research Article
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Cite this article as: eLife 2021;10:e65215 doi: 10.7554/eLife.65215

Abstract

The spatiotemporal distribution of mitochondria is crucial for precise ATP provision and calcium buffering required to support neuronal signaling. Fast-spiking GABAergic interneurons expressing parvalbumin (PV) have a high mitochondrial content reflecting their large energy utilization. The importance for correct trafficking and precise mitochondrial positioning remains poorly elucidated in inhibitory neurons. Miro1 is a Ca²⁺-sensing adaptor protein that links mitochondria to the trafficking apparatus, for their microtubule-dependent transport along axons and dendrites, in order to meet the metabolic and Ca2+-buffering requirements of the cell. Here, we explore the role of Miro1 in parvalbumin interneurons and how changes in mitochondrial trafficking could alter network activity in the mouse brain. By employing live and fixed imaging, we found that the impairments in Miro1-directed trafficking in PV+ interneurons altered their mitochondrial distribution and axonal arborization while PV+ interneuron mediated inhibition remained intact. These changes were accompanied by an increase in the ex vivo hippocampal γ-oscillation (30 – 80 Hz) frequency and promoted anxiolysis. Our findings show that precise regulation of mitochondrial dynamics in PV+ interneurons is crucial for proper neuronal signaling and network synchronization.

Data availability

All data generated or analysed are included in the manuscript, supporting files and source data. The neuronal reconstruction data have been deposited to the NeuroMorpho.Org database.

Article and author information

Author details

  1. Georgina Kontou

    Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Pantelis Antonoudiou

    DPAG, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Marina Podpolny

    Neuroscience, Physiology & Pharmacology, UCL, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Blanka R Szulc

    Neuroscience, Physiology & Pharmacology, UCL, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. I Lorena Arancibia-Carcamo

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0624-3850
  6. Nathalie F Higgs

    Neuroscience, Physiology & Pharmacology, UCL, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Guillermo Lopez-Domenech

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3114-2082
  8. Patricia C Salinas

    Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5748-083X
  9. Edward Mann

    DPAG, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2468-7148
  10. Josef T Kittler

    Neuroscience, Physiology & Pharmacology, UCL, London, United Kingdom
    For correspondence
    j.kittler@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3437-9456

Funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures were carried out in accordance with institutional animal welfare guidelines and licensed by the UK Home Office in accordance with the Animals (Scientific Procedures) Act 1986.

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: November 26, 2020
  2. Accepted: June 25, 2021
  3. Accepted Manuscript published: June 30, 2021 (version 1)
  4. Version of Record published: July 21, 2021 (version 2)

Copyright

© 2021, Kontou 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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