Gephyrin clustering is required for the stability of GABAergic synapses

Although gephyrin is an important postsynaptic scaffolding protein at GABAergic synapses, the role of gephyrin for GABAergic synapse formation and/or maintenance is still under debate. We report here that knocking down gephyrin expression with small hairpin RNAs (shRNAs) in cultured hippocampal pyra...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2007-12, Vol.36 (4), p.484-500
Main Authors: Yu, Wendou, Jiang, Min, Miralles, Celia P., Li, Rong-wen, Chen, Gong, de Blas, Angel L.
Format: Article
Language:English
Subjects:
Animals
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cells, Cultured
Down-Regulation - genetics
gamma-Aminobutyric Acid - metabolism
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Hippocampus - metabolism
Hippocampus - ultrastructure
Inhibitory Postsynaptic Potentials - genetics
Membrane Proteins - genetics
Membrane Proteins - metabolism
Neural Inhibition - genetics
Neural Pathways - metabolism
Neural Pathways - ultrastructure
Presynaptic Terminals - metabolism
Presynaptic Terminals - ultrastructure
Pyramidal Cells - metabolism
Pyramidal Cells - ultrastructure
Rats
Rats, Sprague-Dawley
Receptor Aggregation - genetics
Receptors, GABA-A - genetics
Receptors, GABA-A - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Small Interfering
Synapses - genetics
Synapses - metabolism
Synapses - ultrastructure
Synaptic Transmission - genetics
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Summary:Although gephyrin is an important postsynaptic scaffolding protein at GABAergic synapses, the role of gephyrin for GABAergic synapse formation and/or maintenance is still under debate. We report here that knocking down gephyrin expression with small hairpin RNAs (shRNAs) in cultured hippocampal pyramidal cells decreased both the number of gephyrin and GABA(A) receptor clusters. Similar results were obtained by disrupting the clustering of endogenous gephyrin by overexpressing a gephyrin-EGFP fusion protein that formed aggregates with the endogenous gephyrin. Disrupting postsynaptic gephyrin clusters also had transsynaptic effects leading to a significant reduction of GABAergic presynaptic boutons contacting the transfected pyramidal cells. Consistent with the morphological decrease of GABAergic synapses, electrophysiological analysis revealed a significant reduction in both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). However, no change in the whole-cell GABA currents was detected, suggesting a selective effect of gephyrin on GABA(A) receptor clustering at postsynaptic sites. It is concluded that gephyrin plays a critical role for the stability of GABAergic synapses.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2007.08.008