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The GABA.sub.A Receptor [beta] Subunit Is Required for Inhibitory Transmission

Keywords GABA.sub.A receptor; [beta] subunit; inhibitory transmission; CRISPR/Cas9 Highlights * Functional GABA.sub.A receptors require the [beta] subunit * The [beta]3 subunit is necessary and sufficient for hippocampal inhibitory transmission * Loss of the [beta]3 subunit affects PV- but not SOM-m... Full description

Journal Title: Neuron (Cambridge Mass.), 2018-05-16, Vol.98 (4), p.718
Main Author: Nguyen, Quynh-Anh
Other Authors: Nicoll, Roger A
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Elsevier B.V
ID: ISSN: 0896-6273
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recordid: cdi_gale_infotracacademiconefile_A539156961
title: The GABA.sub.A Receptor [beta] Subunit Is Required for Inhibitory Transmission
format: Article
creator:
  • Nguyen, Quynh-Anh
  • Nicoll, Roger A
subjects:
  • GABA
  • Neurosciences
  • Physiological aspects
ispartof: Neuron (Cambridge, Mass.), 2018-05-16, Vol.98 (4), p.718
description: Keywords GABA.sub.A receptor; [beta] subunit; inhibitory transmission; CRISPR/Cas9 Highlights * Functional GABA.sub.A receptors require the [beta] subunit * The [beta]3 subunit is necessary and sufficient for hippocampal inhibitory transmission * Loss of the [beta]3 subunit affects PV- but not SOM-mediated inhibition * CRISPR/Cas9 allows for combinatorial dissection of multiple molecular components Summary While the canonical assembly of a GABA.sub.A receptor contains two [alpha] subunits, two [beta] subunits, and a fifth subunit, it is unclear which variants of each subunit are necessary for native receptors. We used CRISPR/Cas9 to dissect the role of the GABA.sub.A receptor [beta] subunits in inhibitory transmission onto hippocampal CA1 pyramidal cells and found that deletion of all [beta] subunits 1, 2, and 3 completely eliminated inhibitory responses. In addition, only knockout of [beta]3, alone or in combination with another [beta] subunit, impaired inhibitory synaptic transmission. We found that [beta]3 knockout impairs inhibitory input from PV but not SOM expressing interneurons. Furthermore, expression of [beta]3 alone on the background of the [beta]1-3 subunit knockout was sufficient to restore synaptic and extrasynaptic inhibitory transmission. These findings reveal a crucial role for the [beta]3 subunit in inhibitory transmission and identify a synapse-specific role of the [beta]3 subunit in GABAergic synaptic transmission. Author Affiliation: (1) Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA (2) Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA (3) Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA * Corresponding author Article History: Received 9 June 2017; Revised 24 January 2018; Accepted 26 March 2018 (miscellaneous) Published: April 26, 2018 (footnote)4 Lead Contact Byline: Quynh-Anh Nguyen (1), Roger A. Nicoll [roger.nicoll@ucsf.edu] (2,3,4,*)
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0896-6273
fulltext: fulltext
issn:
  • 0896-6273
  • 1097-4199
url: Link


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titleThe GABA.sub.A Receptor [beta] Subunit Is Required for Inhibitory Transmission
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descriptionKeywords GABA.sub.A receptor; [beta] subunit; inhibitory transmission; CRISPR/Cas9 Highlights * Functional GABA.sub.A receptors require the [beta] subunit * The [beta]3 subunit is necessary and sufficient for hippocampal inhibitory transmission * Loss of the [beta]3 subunit affects PV- but not SOM-mediated inhibition * CRISPR/Cas9 allows for combinatorial dissection of multiple molecular components Summary While the canonical assembly of a GABA.sub.A receptor contains two [alpha] subunits, two [beta] subunits, and a fifth subunit, it is unclear which variants of each subunit are necessary for native receptors. We used CRISPR/Cas9 to dissect the role of the GABA.sub.A receptor [beta] subunits in inhibitory transmission onto hippocampal CA1 pyramidal cells and found that deletion of all [beta] subunits 1, 2, and 3 completely eliminated inhibitory responses. In addition, only knockout of [beta]3, alone or in combination with another [beta] subunit, impaired inhibitory synaptic transmission. We found that [beta]3 knockout impairs inhibitory input from PV but not SOM expressing interneurons. Furthermore, expression of [beta]3 alone on the background of the [beta]1-3 subunit knockout was sufficient to restore synaptic and extrasynaptic inhibitory transmission. These findings reveal a crucial role for the [beta]3 subunit in inhibitory transmission and identify a synapse-specific role of the [beta]3 subunit in GABAergic synaptic transmission. Author Affiliation: (1) Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA (2) Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA (3) Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA * Corresponding author Article History: Received 9 June 2017; Revised 24 January 2018; Accepted 26 March 2018 (miscellaneous) Published: April 26, 2018 (footnote)4 Lead Contact Byline: Quynh-Anh Nguyen (1), Roger A. Nicoll [roger.nicoll@ucsf.edu] (2,3,4,*)
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abstractKeywords GABA.sub.A receptor; [beta] subunit; inhibitory transmission; CRISPR/Cas9 Highlights * Functional GABA.sub.A receptors require the [beta] subunit * The [beta]3 subunit is necessary and sufficient for hippocampal inhibitory transmission * Loss of the [beta]3 subunit affects PV- but not SOM-mediated inhibition * CRISPR/Cas9 allows for combinatorial dissection of multiple molecular components Summary While the canonical assembly of a GABA.sub.A receptor contains two [alpha] subunits, two [beta] subunits, and a fifth subunit, it is unclear which variants of each subunit are necessary for native receptors. We used CRISPR/Cas9 to dissect the role of the GABA.sub.A receptor [beta] subunits in inhibitory transmission onto hippocampal CA1 pyramidal cells and found that deletion of all [beta] subunits 1, 2, and 3 completely eliminated inhibitory responses. In addition, only knockout of [beta]3, alone or in combination with another [beta] subunit, impaired inhibitory synaptic transmission. We found that [beta]3 knockout impairs inhibitory input from PV but not SOM expressing interneurons. Furthermore, expression of [beta]3 alone on the background of the [beta]1-3 subunit knockout was sufficient to restore synaptic and extrasynaptic inhibitory transmission. These findings reveal a crucial role for the [beta]3 subunit in inhibitory transmission and identify a synapse-specific role of the [beta]3 subunit in GABAergic synaptic transmission. Author Affiliation: (1) Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA (2) Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA (3) Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA * Corresponding author Article History: Received 9 June 2017; Revised 24 January 2018; Accepted 26 March 2018 (miscellaneous) Published: April 26, 2018 (footnote)4 Lead Contact Byline: Quynh-Anh Nguyen (1), Roger A. Nicoll [roger.nicoll@ucsf.edu] (2,3,4,*)
pubElsevier B.V
doi10.1016/j.neuron.2018.03.046