Synaptic GABAA receptor clustering without the γ2 subunit

Katalin Kerti-Szigeti, Z. Nusser, Mark D. Eyre

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Rapid activation of postsynaptic GABAA receptors (GABAARs) is crucial in many neuronal functions, including the synchronization of neuronal ensembles and controlling the precise timing of action potentials. Although the γ2 subunit is believed to be essential for the postsynaptic clustering of GABAARs, synaptic currents have been detected in neurons obtained from γ2-/- mice. To determine the role of the γ2 subunit in synaptic GABAAR enrichment, we performed a spatially and temporally controlled γ2 subunit deletion by injecting Cre-expressing viral vectors into the neocortex of GABAARγ277Ilox mice. Whole-cell recordings revealed the presence of miniature IPSCs in Cre+ layer 2/3 pyramidal cells (PCs) with unchanged amplitudes and rise times, but significantly prolonged decays. Such slowly decaying currents could be evoked in PCs by action potentials in presynaptic fast-spiking interneurons. Freeze-fracture replica immunogold labeling revealed the presence of the α1 and β3 subunits in perisomatic synapses of cells that lack the γ2 subunit. Miniature IPSCs in Cre+ PCs were insensitive to low concentrations of flurazepam, providing a pharmacological confirmation of the lack of the γ2 subunit. Receptors assembled from only αβ subunits were unlikely because Zn2+ did not block the synaptic currents. Pharmacological experiments indicated that the αβγ3 receptor, rather than the αβδ, αβε, or αβγ1 receptors, was responsible for the slowly decaying IPSCs. Our data demonstrate the presence of IPSCs and the synaptic enrichment of the α1 and β3 subunits and suggest that the γ3 subunit is the most likely candidate for clustering GABAARs at synapses in the absence of the γ2 subunit.

Original languageEnglish
Pages (from-to)10219-10233
Number of pages15
JournalJournal of Neuroscience
Volume34
Issue number31
DOIs
Publication statusPublished - 2014

Fingerprint

Neurotransmitter Receptor
GABA-A Receptors
Cluster Analysis
Pyramidal Cells
Synapses
Action Potentials
Flurazepam
Pharmacology
Neocortex
Patch-Clamp Techniques
Interneurons
Neurons

Keywords

  • GABA
  • Immunohistochemistry
  • Inhibition
  • Patch-clamp
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Synaptic GABAA receptor clustering without the γ2 subunit. / Kerti-Szigeti, Katalin; Nusser, Z.; Eyre, Mark D.

In: Journal of Neuroscience, Vol. 34, No. 31, 2014, p. 10219-10233.

Research output: Contribution to journalArticle

Kerti-Szigeti, Katalin ; Nusser, Z. ; Eyre, Mark D. / Synaptic GABAA receptor clustering without the γ2 subunit. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 31. pp. 10219-10233.
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