Fig. 4

Loss of NHE9 has pleiotropic effects on hippocampal synaptic transmission. a fEPSPs recorded in CA1 stratum radiatum are reduced in acute hippocampal slices from NHE9 KO mice. Symbols indicate mean ± s.e.m. p = 0.0002 for the difference between genotypes by two-way ANOVA. WT, n = 15 neurons/3 mice; KO, n = 15 neurons/3 mice. b The paired-pulse ratio of fEPSP response at multiple interstimulus intervals (ISIs) shows a significant increase in NHE9 KO slices. Representative traces are shown on the left and mean ± s.e.m. are plotted in the graph at the right. *p < 0.05 by unpaired two-tailed Student’s t test. WT, n = 15 neurons/3 mice; KO, n = 15 neurons/3 mice. c Whole cell recording of evoked EPSCs from pyramidal neurons in CA1 also shows increased PPR at 50 ms ISI in NHE9 KO slices. ****p < 0.0001 by unpaired two-tailed Student’s t test. WT, n = 26 neurons/4 mice; KO, n = 23 neurons/4 mice. d AMPA/NMDA ratios from WT (n = 15 neurons/3 animals) and KO (n = 19 neurons/4 animals) are compared. **p < 0.01. e Whole cell recordings from CA1 neurons of NHE9 KO mice show normal mEPSC amplitude but increased frequency. **p = 0.0098, F-test p = 0.01 by unpaired two-tailed Student’s t test. WT, n = 21 neurons/4 mice; KO, n = 17 neurons/4 mice. f mIPSC amplitude is reduced and the frequency unchanged in NHE9 KO neurons. p = 0.011 by unpaired two-tailed Student’s t test. WT, n = 23 neurons/4 mice; KO, n = 20 neurons/4 mice. g Schematic of single cell KO recording of NHE9 in cKO slices. h, i NHE9 deletion caused equivalent reductions in AMPAR and NMDAR transmission as compared to the simultaneously recorded control neuron. WT, n = 13 neurons/3 mice; KO, n = 13 neurons/3 mice; *p < 0.05 by paired Student’s t test. j No change in paired-pulse ratio was detected in the postsynaptic KO neuron, WT, n = 13 neurons/3 mice; KO, n = 13 neurons/3 mice