Fig. 4
Impairment of ER Ca2+ homeostasis in hippocampal CA1 neurons of IN-PS cDKO mice. Representative IPSCs evoked by 6 repetitive stimulation pulses at 50 Hz (a), 20 Hz (b) and 1.66 Hz (c) recorded before and after addition of the SERCA inhibitor, TG (2 μM for 30 min). Evoked IPSCs obtained from mono-synaptic stimulation in slices from control and IN-PS cDKO mice at 110 µA stimulation intensity. Summary graphs show that GABAergic synaptic responses are decreased in IN-PS cDKO neurons relative to controls (50 Hz: p = 0.012; 20 Hz: p = 0.019; 1.66 Hz: p = 0.011; two-way ANOVA). The TG treatment of slices from control mice results in reduced IPSC amplitudes of CA1 neurons (50 Hz: p = 0.007; 20 Hz: p = 0.013; 1.66 Hz: p = 0.032; two-way ANOVA), whereas TG treatment of slices from IN-PS cDKO mice fails to reduce the amplitude of IPSCs triggered by stimulus trains. d Reduced PPR in IN-PS cDKO mice relative to controls (p = 0.004, two-way ANOVA). The TG treatment of slices from control mice results in reduced PPR (p < 0.0001, two-way ANOVA), whereas TG treatment of slices from IN-PS cDKO mice fails to reduce the PPR. e Summary graphs display individual values of PPR before and after TG application. PPR is significantly decreased after 30 min treatment of TG in control neurons (20 ms: p = 0.0008; 50 ms: p = 0.0006; 600 ms: p = 0.0007; paired t-test), whereas the effect of TG treatment on PPR in IN-PS cDKO neuron is not statistically significant (20 ms: p = 0.51; 50 ms: p = 0.29; 600 ms: p = 0.52; paired t-test). All data represent mean ± SEM (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001; NS: not significant). The number of neurons/mice used in each experiment is shown in parentheses