PT - JOURNAL ARTICLE AU - Sereina Battaglia AU - Marianne Renner AU - Marion Russeau AU - Etienne Côme AU - Shiva K. Tyagarajan AU - Sabine Lévi TI - Activity-Dependent Inhibitory Synapse Scaling Is Determined by Gephyrin Phosphorylation and Subsequent Regulation of GABA<sub>A</sub> Receptor Diffusion AID - 10.1523/ENEURO.0203-17.2017 DP - 2018 Jan 01 TA - eneuro PG - ENEURO.0203-17.2017 VI - 5 IP - 1 4099 - http://www.eneuro.org/content/5/1/ENEURO.0203-17.2017.short 4100 - http://www.eneuro.org/content/5/1/ENEURO.0203-17.2017.full SO - eNeuro2018 Jan 01; 5 AB - Synaptic plasticity relies on the rapid changes in neurotransmitter receptor number at postsynaptic sites. Using superresolution photoactivatable localization microscopy imaging and quantum dot–based single-particle tracking in rat hippocampal cultured neurons, we investigated whether the phosphorylation status of the main scaffolding protein gephyrin influenced the organization of the gephyrin scaffold and GABAA receptor (GABAAR) membrane dynamics. We found that gephyrin phosphorylation regulates gephyrin microdomain compaction. Extracellular signal–regulated kinase 1/2 and glycogen synthase kinase 3β (GSK3β) signaling alter the gephyrin scaffold mesh differentially. Differences in scaffold organization similarly affected the diffusion of synaptic GABAARs, suggesting reduced gephyrin receptor–binding properties. In the context of synaptic scaling, our results identify a novel role of the GSK3β signaling pathway in the activity-dependent regulation of extrasynaptic receptor surface trafficking and GSK3β, protein kinase A, and calcium/calmodulin-dependent protein kinase IIα pathways in facilitating adaptations of synaptic receptors.