Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network

  1. Sam A Booker  Is a corresponding author
  2. Harumi Harada
  3. Claudio Elgueta
  4. Julia Bank
  5. Marlene Bartos
  6. Akos Kulik  Is a corresponding author
  7. Imre Vida  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. University of Freiburg, Germany
  3. Charité - Universitätsmedizin Berlin, Germany

Abstract

Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigate the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rodent hippocampus. Whole-cell recordings from SOM-INs revealed that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also strongly suppressed. Electron microscopic analysis of immunogold-labelled freeze-fracture replicas confirms that GABABRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABABRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. Thus, axonal GABABRs are positioned to efficiently control the input and output synapses of SOM-INs and can functionally uncouple them from local network with implications for rhythmogenesis and the balance of entorhinal versus intrahippocampal afferents.

Data availability

Quantitative electrophysiological, optogenetic and immuno-electron microscopic data presented in the figures and text has been deposited to Dryad (doi:10.5061/dryad.gt160v2).

The following data sets were generated

Article and author information

Author details

  1. Sam A Booker

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    sbooker@exseed.ed.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1980-9873
  2. Harumi Harada

    Institute of Physiology, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7429-7896
  3. Claudio Elgueta

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  4. Julia Bank

    Institute of Physiology, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  5. Marlene Bartos

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    Marlene Bartos, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9741-1946
  6. Akos Kulik

    Institute of Physiology, University of Freiburg, Freiburg, Germany
    For correspondence
    akos.kulik@physiologie.uni-freiburg.de
    Competing interests
    No competing interests declared.
  7. Imre Vida

    Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
    For correspondence
    imre.vida@charite.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3214-2233

Funding

Deutsche Forschungsgemeinschaft (FOR 2134)

  • Marlene Bartos
  • Akos Kulik
  • Imre Vida

Deutsche Forschungsgemeinschaft (BIOSS-2)

  • Akos Kulik

Tenovus

  • Imre Vida

McNaught Bequest, University of Glasgow

  • Sam A Booker
  • Imre Vida

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

Reviewing Editor

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

Ethics

Animal experimentation: Care and handling of the animals prior to and during the experimental procedures followed European Union and national regulations (German Animal Welfare Act; ASPA, United Kingdom Home Office) and all experiments were performed in accordance with institutional guidelines (Charité - Universitätmedizin Berlin; University of Freiburg, Freiburg, Germany), with permissions from local authorities (LaGeSo, Berlin, T-0215/11 LaGeSo; Freiburg, X14/11H and 35-9185.81/G-19/59).

Version history

  1. Received: August 16, 2019
  2. Accepted: February 18, 2020
  3. Accepted Manuscript published: February 19, 2020 (version 1)
  4. Version of Record published: March 6, 2020 (version 2)

Copyright

© 2020, Booker 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. Sam A Booker
  2. Harumi Harada
  3. Claudio Elgueta
  4. Julia Bank
  5. Marlene Bartos
  6. Akos Kulik
  7. Imre Vida
(2020)
Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network
eLife 9:e51156.
https://doi.org/10.7554/eLife.51156

Share this article

https://doi.org/10.7554/eLife.51156

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