LTD is impaired in hippocampal slices derived from TRPM2-/- mice. (a,b) ADPR-primed TRPM2 currents are facilitated by voltage ramps ( ± 100 mV, 1/10 sec) in WT (a), but not in cultured neurons from TRPM2-/- mice (b). (c) Summary bar graph of ADPR-primed peak current amplitude in WT and TRPM2-/- neurons. (unpaired t-test p = 0.001, 553.4 ± 132 pA in WT, n = 5; 7.9 ± 7.2 pA in KO, n = 6) (d) Transient oxygen-glucose deprivation (5 min OGD) causes long-lasting depression of fEPSP slopes in slices from WT (n = 12) but not TRPM2-/- (n = 6). (e) LTP is unaffected by knockout of TRPM2 (WT, n = 6; TRPM2-/-, n = 8). (f) LTD of fEPSPs evoked by repetitive stimulation (900 stimuli at 1 Hz) in WT slices (n = 10) is absent in slices from TRPM2-/- mice (n = 10). (g) LTD of fEPSPs was inhibited by application of clotrimazole, a TRPM2 inhibitor. Timing of clotrimazole application, in treated slices, is indicated by the black bar. (h) Metabotropic-glutamate receptor dependent LTD is unimpaired by deletion of TRPM2 (WT, n = 6; TRPM2-/-, n = 7). (i) Chem-LTD, evoked by 5 min application of NMDA (10 μM) is abolished in slices from TRPM2-/- (n = 6) but not WT (n = 6) slices. (j) Summary graph for a series of recordings from WT and TRPM2-/- slices in which plasticity was induced by repetitive stimulation delivered at 1, 10, 20, 50 Hz (900 pulses at each frequency) or 100 Hz (four 1 sec trains delivered 20 sec apart). For each induction frequency, normalized fEPSP slopes, measured at the end of recording from each of the two populations of slices, are plotted. Numbers in parentheses represents the number of recordings at each point. *denotes p = 0.016.