Chemogenetic isolation reveals synaptic contribution of δ GABAA receptors in mouse dentate granule neurons

Min-Yu Sun, Hong-Jin Shu, Ann Benz, John Bracamontes, Gustav Akk, Charles F. Zorumski, Joe Henry Steinbach and Steven J. Mennerick. Journal of Neuroscience, Volume 38, Issue 38, 19 September 2018, Pages 8128-8145 Read More

Abstract

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. © 2018 the authors.

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Posted on October 8, 2018
Posted in: Axon Injury & Repair, HPAN, Neurodegeneration, Publications Authors: ,