Figure 11.

Overexpression of PSD-95-T19A in CA1 pyramidal neurons blocks induction of LTD. A, Sample traces of evoked AMPA and NMDA receptor EPSCs recorded from transfected CA1 pyramidal neurons (identified by cotransfected GFP) versus untransfected controls. B, AMPA receptor (left) and NMDA receptor (right) EPSCs from transfected neurons versus neighboring untransfected controls. Average EPSC ±SEM for each treatment is indicated in red. PSD-95-T19A, n = 24 (AMPA), 22 (NMDA) pairs; wt-PSD-95, n = 33, 33 pairs; PSD-95-T19D, n = 23, 22 pairs. C, Summary of PSD-95-T19 mutant overexpression on AMPA-R-EPSCs (top) and NMDA-R-EPSCs (bottom), as indicated by the ratio of EPSC amplitudes between transfected and neighboring untransfected cells. Statistical significance was determined by paired t test (*p < 0.05). D, CA1 neurons were transfected with wild-type or mutant PSD-95 as indicated and recorded together with untransfected neighboring cells in double whole-cell patch-clamp mode. LTD was induced by a pairing protocol (see Materials and Methods). Statistical significance was determined by two-tailed t test on mean normalized EPSC (averaged over the last 10 min of postinduction recordings) for LTD experiments (n = 10, 8, and 9 pairs from left to right; **p < 0.01).