Fig. 6

Inhibition of mitochondrial Ca²⁺ release mimics and occludes deficits of mitochondrial Ca²⁺ homeostasis in hippocampal DG granule neurons of PS cDKO mice. a Representative Ca²⁺ transients evoked by 10 repetitive stimulation (depolarizing pulses of 2 ms duration; from −80 to 0 mV) at 20 Hz recorded in the absence or presence of CGP37157. Scale bar: 2 s, 100 nM. b Summary bar graph of the amplitude of ∆[Ca²⁺]_i shows significant reduction in PS cDKO granule neurons (250.7 ± 19.7 nM, unpaired t-test, p < 0.001) and control granule neurons treated with CGP37157 (289.2 ± 12.1 nM, paired t-test, p < 0.001), relative to untreated control neurons (360.1 ± 11.4 nM). Bar graphs represent means ± SEM (*** p < 0.001; Student’s t-test, NS: not significant). c The amplitude of ∆[Ca²⁺]_i elicited by PTP inducing stimulation (16 pulses at 100 Hz, 4 times delivered at 0.33 Hz; from −80 to 0 mV) is significantly reduced in PS cDKO granule neurons and control granule neurons treated with CGP37157, relative to untreated control neurons (control vs PS cDKO: F_{1, 15} = 12.56, p = 0.0029, control vs control + CGP: F_{1, 14} = 28.46, p = 0.0001; two-way ANOVA). CGP37157 treatment does not significantly reduce ∆[Ca²⁺]_i in PS cDKO neurons (F_{1, 16} = 0.76, p = 0.40; two-way ANOVA). The insets are averaged Ca²⁺ transients. The values in parentheses indicate the number of neurons (left) and the number of mice (right) used in each experiment