Benzodiazepine-dependent stabilization of GABA(A) receptors at synapses

Molecular and Cellular Neurosciences
Geraldine GouzerAntoine Triller

Abstract

GABA(A) receptors constitutively enter and exit synapses by lateral diffusion in the plane of the neuronal membrane. They are trapped at synapses through their interactions with gephyrin, the main scaffolding protein at inhibitory post-synaptic densities. Previous work has shown that the synaptic accumulation and diffusion dynamics of GABA(A)Rs are controlled via excitatory synaptic activity. However, it remains unknown whether GABA(A)R activity can itself impact the surface trafficking of the receptors. Here we report the effects of GABA(A)R agonists, antagonists and allosteric modulators on the receptor's surface dynamics. Using immunocytochemistry and single particle tracking experiments on mouse hippocampal neurons, we show that the agonist muscimol decreases GABA(A)R and gephyrin levels at synapses and accelerates the receptor's lateral diffusion within 30–120 min of treatment. In contrast, the GABA(A)R antagonist gabazine increased GABA(A)R amounts and slowed down GABA(A)R diffusion at synapses. The response to GABA(A)R activation or inhibition appears to be an adaptative regulation of GABAergic synapses. Surprisingly, the positive allosteric modulator diazepam abolished the regulation induced by muscimol, and this effect...Continue Reading

References

Jan 14, 1998·Trends in Pharmacological Sciences·E Sigel, A Buhr
Jan 17, 2002·The Journal of Comparative Neurology·Ina BrünigJean-Marc Fritschy
Sep 5, 2002·Nature Reviews. Neuroscience·Yehezkel Ben-Ari
Mar 25, 2005·The European Journal of Neuroscience·Stanislav KhirugLeonard Khiroug
Jun 2, 2005·Trends in Neurosciences·Alain Marty, Isabel Llano
Jun 14, 2005·Nature Neuroscience·Philip ThomasTrevor G Smart
Nov 11, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tija C JacobStephen J Moss
Apr 12, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard W Olsen
Sep 2, 2006·The EMBO Journal·Yury BogdanovStephen J Moss
Sep 26, 2006·The Journal of Comparative Neurology·David R SerwanskiAngel L De Blas
Feb 13, 2007·Biophysical Journal·Marie-Virginie EhrenspergerMaxime Dahan
May 15, 2007·Progress in Brain Research·Mark Farrant, Kai Kaila
Nov 30, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Richard S SalibaStephen J Moss
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Verena TretterStephen J Moss
Aug 15, 2008·Neuron·Antoine Triller, Daniel Choquet
Mar 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marianne RennerAntoine Triller
Apr 28, 2009·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Ken Sekimoto, Antoine Triller
Feb 4, 2010·Pharmacological Reviews·Mikko Uusi-Oukari, Esa R Korpi
Jul 14, 2010·The Journal of Biological Chemistry·Leila SaiepourKirsten Harvey
Jul 27, 2010·Current Opinion in Neurobiology·Kimberly Gerrow, Antoine Triller
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·James MuirJosef T Kittler
Jan 7, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patricia MachadoAntoine Triller
May 11, 2011·Neuron·Bernhard LuscherCasey L Kilpatrick
Aug 11, 2011·The EMBO Journal·Christian G SpechtAntoine Triller
Oct 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jayanta MukherjeeStephen J Moss
Oct 19, 2011·The Journal of Biological Chemistry·Hans-Michael MaricHermann Schindelin
May 9, 2012·PloS One·Fumihiro NiwaKatsuhiko Mikoshiba
May 23, 2012·Frontiers in Cellular Neuroscience·Verena TretterStephen J Moss
Aug 23, 2012·PloS One·Marianne RennerSabine Lévi
Oct 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tija C JacobStephen J Moss

Citations

Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jayanta MukherjeeStephen J Moss
Sep 14, 2017·Developmental Neurobiology·Joshua M Lorenz-Guertin, Tija C Jacob
Sep 8, 2018·Frontiers in Cellular Neuroscience·Joshua M Lorenz-GuertinTija C Jacob
May 14, 2019·Frontiers in Cellular Neuroscience·Joshua M Lorenz-GuertinTija C Jacob
Jan 11, 2020·Frontiers in Molecular Neuroscience·Stephanie A Maynard, Antoine Triller
Jul 11, 2020·European Archives of Psychiatry and Clinical Neuroscience·M DeppeM Schecklmann
Dec 5, 2020·Journal of Clinical Pharmacology·Rebecca H StoneWilliam Kobak

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