Fig. 5

TAT-STEP WT blocks synaptic scaling induced by prolonged inhibition of hippocampal network activity. a–d Whole-cell patch clamp recording of mEPSCs from cultured hippocampal neurons that were treated for 48 h with vehicle control (CTL, 0.1 % H₂O) and TTX (1 μM). Prior to mEPSCs recording, neurons were preincubated for 30 min with TAT-myc and TAT-STEP WT protein. a Representative traces of mEPSCs. b Normalized cumulative fraction of the mEPSC amplitudes. c TAT-STEP WT abolished the TTX-induced increase in the mEPSC amplitudes. d TAT-STEP WT did not affect the mEPSC frequencies. Data shown (c, d) represent the mean ± SEM (*p < 0.05). e Model by which activity-dependent changes in STEP₆₁ level and activity regulate Tyr-dephosphorylation of GluA2 and GluN2B, leading to changes in surface AMPAR and NMDAR expression during homeostatic synaptic plasticity. Gray arrows indicate internalization. Orange arrows indicate lateral movement of surface AMPAR and NMDAR out of postsynaptic density (light pink)