Fig. 5

Activation of mGluR4 rescues PF-PC LTP in Fmr1KO slices. a LAP4 (40 μM) and the mGluR4 PAM VU 0155041 (100 μM) rescues PF-PC LTP in Fmr1KO slices. The β-AR antagonist propranolol (100 µM) was added 30 min prior to LTP induction. b Quantification of EPSC amplitude (mean of 6 consecutive EPSCs delivered at 0.05 Hz) 30 min after stimulation (2) compared to the respective values before stimulation (1): LAP4 (n = 10 cells/10 slices/5 mice); VU (n = 11 cells/11 slices/6 mice); propranolol + VU (n = 10 cells, 10 slices/6 mice). c Cumulative EPSC amplitudes in Fmr1KO slices in the presence or absence (basal) of VU (100 μM, 10 min) and before (VU) and 30 min after 10 Hz stimulation (VU + 10 Hz). d Quantification of the RRP size in the above conditions: Basal (n = 10 cells/10 slices/7 mice); VU (n = 12 cells/10 slices/7 mice: **P < 0.01 compared to basal); VU plus 10 Hz (n = 8 cells/8 slices/4 mice: ^##P < 0.01, compared to VU alone). e VU restores Ca²⁺ dynamics to Fmr1KO cerebellar synaptosomes. Changes in the cytoplasmic free Ca²⁺ concentration ([Ca²⁺]_c) in the presence and absence of VU (100 µM) added at least 5 min prior to KCl. f Quantification of the changes in [Ca²⁺]_c: KCl/WT (n = 18/5 preparations); KCl/Fmr1 KO (n = 16/5 preparations: ^###P < 0.001 compared to KCl/WT); VU/KCl/WT (n = 11/4 preparations); and VU/KCl/Fmr1KO (n = 12/4 preparations). g Scheme showing the preparation of cerebellar slices from VU or saline injected Fmr1KO mice. h Response to a 10 Hz stimulation in slices from VU and saline injected Fmr1KO mice i amplitude (mean of 6 consecutive EPSCs delivered at 0.05 Hz) 30 min after stimulation (2) compared to the respective values before stimulation (1): VU (5 mg/Kg) injected Fmr1KO mice (n = 14 cells/14 slices/10 mice); saline injected Fmr1KO mice (n = 10 cells/10 slices/8 mice). Bar graphs show raw data and the mean. Scale bars in (a, h) 100 pA and 10 ms. Unpaired Student’s t test in (b, d). Two-way ANOVA followed by Tukey in (f). Welch test in (i). *P < 0.05, **P < 0.01, ***P < 0.001