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

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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 GABA_B receptors (GABA_BRs) in the rodent hippocampus. Whole-cell recordings from SOM-INs revealed that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABA_BRs, 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 GABA_BRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABA_BRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. Thus, axonal GABA_BRs 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

1. Booker SA
2. Harada H
3. Elgueta C
4. Bank J
5. Bartos M
6. Kulik A
7. Vida I
(2020) Presynaptic GABAB Receptors Functionally Uncouple Somatostatin Interneurons from the Active Hippocampal Network
Dryad Digital Repository, doi:10.5061/dryad.gt160v2.

http://dx.doi.org/10.5061/dryad.gt160v2

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0003-1980-9873
Harumi Harada

Institute of Physiology, University of Freiburg, Freiburg, Germany

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7429-7896
Claudio Elgueta

Institute for Physiology I, University of Freiburg, Freiburg, Germany

Competing interests
No competing interests declared.
Julia Bank

Institute of Physiology, University of Freiburg, Freiburg, Germany

Competing interests
No competing interests declared.
Marlene Bartos

Institute for Physiology I, University of Freiburg, Freiburg, Germany

Competing interests
Marlene Bartos, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-9741-1946
Akos Kulik

Institute of Physiology, University of Freiburg, Freiburg, Germany

For correspondence
akos.kulik@physiologie.uni-freiburg.de

Competing interests
No competing interests declared.
Imre Vida

Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany

For correspondence
imre.vida@charite.de

Competing interests
No competing interests declared.

"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.

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).

Copyright

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.