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 journal › SCORING: Journal article › Research › peer-review
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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 -