We recently showed that pairing low-frequency presynaptic activity with postsynaptic depolarization evokes NMDAR-mediated Hebbian LTP in hippocampal CA1 feed-forward inhibitory interneurons (Lamsa et al, SFN 2004). Here we report that NMDARs in interneurons require constitutive activation by Src-family kinases (SFKs). We isolated NMDAR-mediated EPSPs in stratum radiatum interneurons of rat slices by recording in picrotoxin (100 µM), NBQX (10 µM) and 0 [Mg2+]. NMDAR-mediated EPSPs were detected in every one of 54 cells recorded via a gramicidin perforated patch. SFK inhibitors (10 µM lavendustin A or 50 µM genistein) reversibly attenuated NMDAR-mediated EPSPs. When recorded in whole-cell mode, NMDAR-mediated EPSP/Cs attenuated rapidly or disappeared altogether, in contrast to AMPA/kainateR-mediated responses which remained stable. Run-down was prevented when the Src-activating peptide [H]EPQ[pTyr]EEPIA[OH] (10 µM) was included in the pipette. Run-down could also be reversed by withdrawing the whole-cell pip...