Fig. 6.

Bi-directional pharmacological manipulation of RyR1 modulates tremor in RyR1 S2844D ^+/+ mice by agonist caffeine and antagonist dantrolene. a Representative time–frequency plot following intraperitoneal (IP) injections of caffeine in RyR1-S2844D^+/+ mice, with b corresponding spectral diagram and c tremor quantification showing increased tremor by IP caffeine injection. d Representative time–frequency plot following IP injections of dantrolene in RyR1-S2844D^+/+ mice, with e corresponding spectral diagram and f tremor quantification showing decreased tremor by IP dantrolene injection. (n = 6 mice at 6–12 months old for each ligand. [**p < 0.01 by two-tailed paired t test] g A representative time–frequency plot following cerebellar microinfusion of caffeine in RyR1-S2844D^+/+ mice, with h corresponding spectral diagram and i tremor quantification showing increased tremor by intracerebellar caffeine infusion. j A representative time–frequency plot following cerebellar microinfusion of dantrolene in RyR1-S2844D^+/+ mice, with k corresponding spectral diagram and l tremor quantification showing decreased tremor by intracerebellar dantrolene infusion. (n = 3 mice at 6–12 months old for each ligand, two independent runs for each mouse). PSD power spectral density. ***p < 0.001, ****p < 0.0001 by two-tailed paired t test