Access (7–18 MΩ) and membrane resistance (see Table S1) were monitored before and after mEPSC recordings and data were rejected if changes greater than 20% occurred. The behavioral experiments started 3 weeks after stereotaxic delivery of rAAVs. Mice were habituated to the experimental room and handled once a day for 3 consecutive days before testing started. Two different sets of mice were used for

Morris water maze Dasatinib clinical trial and contextual fear conditioning experiments. At the end of the experiments, virus infection was assessed. For details on the behavioral experiments see Supplemental Information. All plotted data represent mean ± SEM. ANOVA with Tukey’s post hoc test was used for statistical analyses except where stated otherwise. In those experiments where only two conditions are tested, comparisons were made by using a Student’s t test for independent samples. In the Morris water maze experiment,

repeated-measures ANOVA and Baf-A1 datasheet one-way ANOVA were used to analyze acquisition curves and probe trials, respectively. We thank I. Bünzli-Ehret for her help with the preparation of hippocampal cultures; U. Weiss for western blot analysis; Drs. S. Oliviero, B.L. Sabatini, and A. Asano for providing plasmids; Drs. S.J. Zhang, D. Lau, and S. Romorini for discussions; and Dr. A.M. Hagenston for comments on the manuscript. All images of Golgi-impregnated tissues were taken at the Nikon Imaging Center at Heidelberg University. This work was supported by the Alexander von Humboldt Foundation (Wolfgang Paul Prize to H.B.), a European Research Council (ERC) Advanced Grant (to H.B.), the Sonderforschungsbereich (SFB) 488 and SFB 636 of the Deutsche Forschungsgemeinschaft (DFG),

the European Network of Excellence NeuroNE, and the Histone demethylase European Union Project Glutamate Receptor Interacting Proteins as Novel Neuroprotective Targets (EU Project GRIPANNT). H.B. is a member of the Excellence Cluster “CellNetworks” at Heidelberg University. D.M. is recipient of a European Molecular Biology Organization (EMBO) Long-Term Fellowship; A.M.M.O. is recipient of a Postdoctoral Fellowship from the Foundation for Science and Technology, Portugal. “
“PSD-95, the principal protein of postsynaptic densities (PSD), is a major scaffolding protein that impacts synaptic plasticity (Cho et al., 1992 and Migaud et al., 1998). In addition to maintaining the molecular architecture of the PSD (Chen et al., 2008), PSD-95 enhances long-term depression (Stein et al., 2003) and is required for spatial learning in mouse models (Migaud et al., 1998). N-terminal palmitoylation targets PSD-95 to synapses, where it clusters AMPA-type glutamate receptors (Chen et al., 2000) and physically links NMDA receptors to neuronal nitric oxide synthase (nNOS) (Brenman et al., 1996 and Christopherson et al., 1999). This interaction enables calcium that permeates NMDA receptors to activate nNOS by binding calmodulin associated with the enzyme (Bredt and Snyder, 1990).