Extrasynaptic GluN2B homeostasis is recruited after glutamate spillover. A: 5-Hz stimulation for 30 s delivered at time = 0 induced indistinguishable robust long-term potentiation (LTP) in vehicle control experiments and in the presence of ifenprodil 5 μM. Field excitatory postsynaptic potentials (fEPSPs) were 146.7% of baseline 45 min after 5-Hz stimulation for control (○, n = 8 from 6 animals) and 143.7% of baseline in the presence of ifenprodil (●, n = 5 from 5 animals); P = 0.93. B: 5-Hz, 30-s stimulation delivered at time = 0 induced robust LTP (fEPSPs were 166.5% of baseline in vehicle control experiments; ○, n = 6 from 6 animals) but was significantly impaired in the presence of the glutamate transporter blocker DL-threo-beta-benzyloxyaspartic acid (TBOA) 10 μM (fEPSPs were 119.2% of baseline; ●, n = 6 from 5 animals; P < 0.001 compared with controls). C: 5-Hz stimulation for 30 s induced indistinguishable robust LTP in vehicle control experiments (○, n = 11 from 10 animals, fEPSPs were 160.4% of baseline) and when delivered in the presence of TBOA 10 μM and ifenprodil 5 μM (●, n = 8 from 7 animals; fEPSPs were 161.3% of baseline); P = 0.91. D: summary of the data presented in A–C. Bar graph indicates the average fEPSP obtained from the last 5 min of recording for each condition (***P < 0.001 compared with untreated controls). IFEN, ifenprodil.