Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP

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Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. / Petrini, Enrica Maria; Ravasenga, Tiziana; Hausrat, Torben J; Iurilli, Giuliano; Olcese, Umberto; Racine, Victor; Sibarita, Jean-Baptiste; Jacob, Tija C; Moss, Stephen J; Benfenati, Fabio; Medini, Paolo; Kneussel, Matthias; Barberis, Andrea.

In: NAT COMMUN, Vol. 5, 01.01.2014, p. 3921.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Petrini, EM, Ravasenga, T, Hausrat, TJ, Iurilli, G, Olcese, U, Racine, V, Sibarita, J-B, Jacob, TC, Moss, SJ, Benfenati, F, Medini, P, Kneussel, M & Barberis, A 2014, 'Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP', NAT COMMUN, vol. 5, pp. 3921. https://doi.org/10.1038/ncomms4921

APA

Petrini, E. M., Ravasenga, T., Hausrat, T. J., Iurilli, G., Olcese, U., Racine, V., Sibarita, J-B., Jacob, T. C., Moss, S. J., Benfenati, F., Medini, P., Kneussel, M., & Barberis, A. (2014). Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. NAT COMMUN, 5, 3921. https://doi.org/10.1038/ncomms4921

Vancouver

Bibtex

@article{af9ac6a0cfb14e72808e93c4853a4bb3,
title = "Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP",
abstract = "Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABA(A)Rs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance the clustering of postsynaptic GABA(A)Rs during iLTP remain obscure. Here we demonstrate that during chemically induced iLTP (chem-iLTP), GABA(A)Rs are immobilized and confined at synapses, as revealed by single-particle tracking of individual GABA(A)Rs in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment of the scaffold protein gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent phosphorylation of GABA(A)R-β3-Ser(383). Impairment of gephyrin assembly prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization of GABA(A)Rs at synapses. Importantly, an increase of gephyrin and GABA(A)R similar to those observed during chem-iLTP in cultures were found in the rat visual cortex following an experience-dependent plasticity protocol that potentiates inhibitory transmission in vivo. Thus, phospho-GABA(A)R-β3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.",
author = "Petrini, {Enrica Maria} and Tiziana Ravasenga and Hausrat, {Torben J} and Giuliano Iurilli and Umberto Olcese and Victor Racine and Jean-Baptiste Sibarita and Jacob, {Tija C} and Moss, {Stephen J} and Fabio Benfenati and Paolo Medini and Matthias Kneussel and Andrea Barberis",
year = "2014",
month = jan,
day = "1",
doi = "10.1038/ncomms4921",
language = "English",
volume = "5",
pages = "3921",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP

AU - Petrini, Enrica Maria

AU - Ravasenga, Tiziana

AU - Hausrat, Torben J

AU - Iurilli, Giuliano

AU - Olcese, Umberto

AU - Racine, Victor

AU - Sibarita, Jean-Baptiste

AU - Jacob, Tija C

AU - Moss, Stephen J

AU - Benfenati, Fabio

AU - Medini, Paolo

AU - Kneussel, Matthias

AU - Barberis, Andrea

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABA(A)Rs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance the clustering of postsynaptic GABA(A)Rs during iLTP remain obscure. Here we demonstrate that during chemically induced iLTP (chem-iLTP), GABA(A)Rs are immobilized and confined at synapses, as revealed by single-particle tracking of individual GABA(A)Rs in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment of the scaffold protein gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent phosphorylation of GABA(A)R-β3-Ser(383). Impairment of gephyrin assembly prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization of GABA(A)Rs at synapses. Importantly, an increase of gephyrin and GABA(A)R similar to those observed during chem-iLTP in cultures were found in the rat visual cortex following an experience-dependent plasticity protocol that potentiates inhibitory transmission in vivo. Thus, phospho-GABA(A)R-β3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.

AB - Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABA(A)Rs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance the clustering of postsynaptic GABA(A)Rs during iLTP remain obscure. Here we demonstrate that during chemically induced iLTP (chem-iLTP), GABA(A)Rs are immobilized and confined at synapses, as revealed by single-particle tracking of individual GABA(A)Rs in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment of the scaffold protein gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent phosphorylation of GABA(A)R-β3-Ser(383). Impairment of gephyrin assembly prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization of GABA(A)Rs at synapses. Importantly, an increase of gephyrin and GABA(A)R similar to those observed during chem-iLTP in cultures were found in the rat visual cortex following an experience-dependent plasticity protocol that potentiates inhibitory transmission in vivo. Thus, phospho-GABA(A)R-β3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.

U2 - 10.1038/ncomms4921

DO - 10.1038/ncomms4921

M3 - SCORING: Journal article

C2 - 24894704

VL - 5

SP - 3921

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -