Fig. 4

Synaptic transmission and plasticity are impaired in L100P mutant hippocampus. a sEPSCs in dentate granule cells. Top, sample sEPSCs traces recorded in L100P (right) and WT (left) granule cells. Bottom, summary of sEPSCs frequency (left) and amplitude (right) showing reduced sEPSCs frequency and amplitude in L100P granule cells compared to the WT controls. **P < 0.01 or *** P < 0.001, unpaired t-test, n = 9 (5 mice) for WT group and n = 11 (5 mice) for L100P group. Scale bars, 20 pA and 200 ms. b mEPSCs recorded in dentate granule cells. Top, sample mEPSCs traces recorded in L100P (right) and WT (left) granule cells. Bottom, summary of mEPSCs frequency (left) and amplitude (right) showing reduced mEPSCs frequency and amplitude in L100P granule cells compared to the WT controls. *P < 0.05, unpaired t-test, n = 10 (5 mice) for WT group and n = 11 (5 mice) for L100P group. Scale bars, 20 pA and 200 ms. c sIPSCs in CA1 pyramidal cells. Left, sample sIPSCs traces recorded in L100P (bottom) and WT (top) pyramidal cells. Summary of sIPSCs frequency (middle) and amplitude (right) showing reduced sIPSCs amplitude but normal frequency in L100P cells compared to the WT controls. *P < 0.01, unpaired t-test, n = 9 (5 mice) for WT group and n = 11 (5 mice) for L100P group. Scale bars, 100 pA and 200 ms. d I/O relationship between the fiber volley amplitude and fEPSP slope in hippocampal SC-CA1 synapses. Each point represents the mean of all slices tested for certain stimulus intensity. Error bars illustrate standard error for both axes. WT and L100P slices exhibit similar average I/O slope. P > 0.05, unpaired t-test, n = 24 (6 mice) for WT group and n = 18 (5 mice) for L100P group. e Paired-pulse ratio across different interpulse intervals in hippocampal SC-CA1 synapses. L100P group shows reduced paired-pulse facilitation. Two-way repeated measure ANOVA and Bonferroni post-tests, **P < 0.01 at interval of 100 ms, n = 12 slices from 5 mice for each group. f LTP induced by 100Hz (1 s) stimulus in hippocampal SC-CA1 synapses. fEPSP slopes normalized to the average baseline response (10 min) before LTP induction (time 0), are plotted in 1-min blocks. Sample traces show responses during baseline and the last 10 min of the recording (average of 10 recording traces). Scale bars, 0.1 mV and 4 ms. g Averaged percentage change of fEPSP slope after LTP induction showing reduced PTP (first 5 min of recording) and LTP (last 10 min of recording) in L100P mutant hippocampal SC-CA1 synapses. *P < 0.05, unpaired t-test, n = 21 slices from 6 WT mice, n = 14 slices from 5 L100P mutant mice. All data are shown as means ± SEM.