Chemogenetic Isolation Reveals Synaptic Contribution of δ GABA^sub A^ Receptors in Mouse Dentate Granule Neurons

Two major GABAA receptor classes mediate ionotropic GABA signaling, those containing a δ subunit and those with a γ2 subunit. The classical viewpoint equates γ2-containing receptors with IPSCs and δ-containing receptors with tonic inhibition because of differences in receptor localization, but signi...

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Bibliographic Details
Published in:The Journal of neuroscience 2018-09, Vol.38 (38), p.8128
Main Authors: Sun, Min-Yu, Shu, Hong-Jin, Benz, Ann, Bracamontes, John, Akk, Gustav, Zorumski, Charles F, Steinbach, Joe Henry, Mennerick, Steven J
Format: Article
Language:English
Subjects:
Cerebral cortex
Genetic modification
Granular materials
Granule cells
Inhibition
Inhibitory postsynaptic potentials
Localization
Neurons
Pharmacology
Picrotoxin
Point mutation
Receptors
Thalamus
γ-Aminobutyric acid A receptors
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Summary:Two major GABAA receptor classes mediate ionotropic GABA signaling, those containing a δ subunit and those with a γ2 subunit. The classical viewpoint equates γ2-containing receptors with IPSCs and δ-containing receptors with tonic inhibition because of differences in receptor localization, but significant questions remain because the populations cannot be pharmacologically separated. We removed this barrier using gene editing to confer a point mutation on the δ subunit in mice, rendering receptors containing the subunit picrotoxin resistant. By pharmacologically isolating δ-containing receptors, our results demonstrate their contribution to IPSCs in dentate granule neurons and weaker contributions to thalamocortical IPSCs. Despite documented extrasynaptic localization, we found that receptor localization does not preclude participation in isolated IPSCs, including mIPSCs. Further, phasic inhibition from δ subunit-containing receptors strongly inhibited summation of EPSPs, whereas tonic activity had little impact. In addition to any role that δ-containing receptors may play in canonical tonic inhibition, our results highlight a previously underestimated contribution of δ-containing receptors to phasic inhibition.
ISSN:0270-6474
1529-2401