RT Journal Article SR Electronic T1 Activity-Dependent Inhibitory Synapse Scaling Is Determined by Gephyrin Phosphorylation and Subsequent Regulation of GABAA Receptor Diffusion JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0203-17.2017 DO 10.1523/ENEURO.0203-17.2017 VO 5 IS 1 A1 Sereina Battaglia A1 Marianne Renner A1 Marion Russeau A1 Etienne Côme A1 Shiva K. Tyagarajan A1 Sabine Lévi YR 2018 UL http://www.eneuro.org/content/5/1/ENEURO.0203-17.2017.abstract 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.