Differential modulation of short-term plasticity at hippocampal mossy fiber and Schaffer collateral synapses by mitochondrial Ca2+
Fig 2
Differential effects of mitochondiral NCX inhibitors on PTP at MF and SC synapses.
PTP was induced by high frequency stimulation (HFS: 16 pulses at 100 Hz, 4 times delivered at 0.33 Hz) in acute hippocampal slices of wild-type mice at 2 months of age. (A & B) Mean value of time-dependent changes in the fEPSP slope was recorded in the absence (A) or presence (B) of CGP37157 (20 μM), a mitochondrial NCX inhibitor, in the hippocampal MF pathway. The insets represent traces recorded before and immediately after HFS. DCG-4 (2 μM) was applied at the end of all experiments to confirm the recording of MF synapses. (C) The summary bar graph for the mean magnitude of PTP shows that PTP is reduced by CGP37157 treatment at MF synapses (Control: 219.1 ± 12.0%; +CGP: 157.1 ± 5.2%; p = 0.00013, paired t-test). (D) The effect of CGP37157 on basal transmission. Treatment of CGP37157 for 15 min has no effect on the fEPSP slope at MF synapses. (E & F) Mean value of time-dependent changes in the fEPSP slope was recorded in the absence (E) or presence (F) of TPP+ (2 μM), another specific inhibitor of mitochondrial NCX, in the hippocampal MF pathway. (G) The summary bar graph for the mean magnitude of PTP further shows that PTP induction is reduced at MF synapses (Control: 194.0 ± 5.2%; +TPP: 147.2 ± 2.7%; p < 0.0001, paired t-test). (H) The effect of TPP+ on basal transmission. Treatment of TPP+ for 15 min has no effect on the fEPSP slope at MF synapses. (I & J) Mean value of time-dependent changes in the fEPSP slope before and after the PTP induction in the hippocampal SC pathway. The insets represent traces recorded before and immediately after HFS. The effect of treatment with CGP37157 on PTP of fEPSPs at the hippocampal SC pathway shows that inhibition of mitochondrial Ca2+ release had no effect on PTP induction. (K) The summary bar graph for the mean magnitude of PTP shows that PTP induction is not different at SC synapses in the absence or the presence of CGP37157 treatment (Control: 234.7 ± 9.8%; +CGP: 222.7 ± 6.9%; p = 0.17, paired t-test). (L) The effect of CGP37157 on basal transmission. Treatment of CGP37157 for 15 min has no effect on the fEPSP slope at SC synapses. All data represent mean ± SEM (*** p < 0.001, **** p < 0.0001, NS: not significant; Student’s t-test). The value in parentheses indicates the number of hippocampal slices (left) and the number of mice (right) used in each experiment. Scale bar: 10 ms, 0.5 mV.