Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex

Abstract

Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron types is poorly known. We investigated GABAergic parvalbumin-expressing basket cells (pvBCs) in layer 2/3 (L2/3) in human neocortical tissue resected in deep-brain surgery, and in mice as control. Most pvBCs showed robust GABAAR-mediated self-innervation in both species, but autapses were rare in nonfast-spiking GABAergic interneurons. Light- and electron microscopy analyses revealed pvBC axons innervating their own soma and proximal dendrites. GABAergic self-inhibition conductance was similar in human and mouse pvBCs and comparable to that of synapses from pvBCs to other L2/3 neurons. Autaptic conductance prolonged somatic inhibition in pvBCs after a spike and inhibited repetitive firing. Perisomatic autaptic inhibition is common in both human and mouse pvBCs of supragranular neocortex, where they efficiently control discharge of the pvBCs.

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All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Viktor Szegedi

    MTA-NAP Research Group for Inhibitory Interneurons and Plasticity, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    For correspondence
    szegediv@bio.u-szeged.hu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4191-379X
  2. Melinda Paizs

    MTA-NAP Research Group for Inhibitory Interneurons and Plasticity, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Judith Baka

    MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Pál Barzó

    Department of Neurosurgery, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Gábor Molnár

    MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Gabor Tamas

    MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7905-6001
  7. Karri Lamsa

    MTA-NAP Research Group for Inhibitory Interneurons and Plasticity, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary
    For correspondence
    klamsa@bio.u-szeged.hu
    Competing interests
    The authors declare that no competing interests exist.

Funding

NKFIH (National Brain Research Programme)

  • Viktor Szegedi
  • Melinda Paizs
  • Karri Lamsa

ERC (INTERIMPACT)

  • Gabor Tamas

Hungarian Academy of Sciences

  • Viktor Szegedi
  • Gábor Molnár

University of Szeged Open Access Fund (4373)

  • Viktor Szegedi
  • Karri Lamsa

Eotvos Lorand Research Network

  • Gabor Tamas

National Research, Development and Innovation Office of Hungary (GINOP-2.3.2-15-2016-00018)

  • Gabor Tamas

National Research, Development and Innovation Office (OTKA K128863)

  • Gábor Molnár
  • Gabor Tamas
  • Karri Lamsa

Ministry of Human Capacities Hungary (20391-3/2018/FEKUSTRAT)

  • Gabor Tamas
  • Karri Lamsa

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 procedures were performed with the approval of theUniversity of Szeged (no. I-74-8/2016) and in accordance withthe Guide for the Care and Use of Laboratory Animals (2011)(http://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-oflaboratory-animals.pdf).

Human subjects: All procedures were performed according to the Declaration of Helsinki with the approval of the University of Szeged Ethical Committee and Regional Human Investigation Review Board (ref. 75/2014). For all human tissue material, written consent was obtained from patients prior to surgery. Tissue obtained from underage patients was provided with agreement from a parent or guardian.

Reviewing Editor

  1. John Huguenard, Stanford University School of Medicine, United States

Publication history

  1. Received: September 6, 2019
  2. Accepted: January 8, 2020
  3. Accepted Manuscript published: January 9, 2020 (version 1)
  4. Version of Record published: January 27, 2020 (version 2)

Copyright

© 2020, Szegedi 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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  1. Viktor Szegedi
  2. Melinda Paizs
  3. Judith Baka
  4. Pál Barzó
  5. Gábor Molnár
  6. Gabor Tamas
  7. Karri Lamsa
(2020)
Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex
eLife 9:e51691.
https://doi.org/10.7554/eLife.51691
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