Increasing IP3R1 sensitivity to IP3 can restore normal calcium response in the context of reduced IP3R1 levels (a model of SCA15/16). a, Coincident calcium release (from 4 parallel fiber stimuli and a single climbing fiber stimulus) with IP3R1 levels decreased to 50% and 10%. b, Wild type levels of supralinear calcium release can be regained in IP3R1 insufficiency by augmenting IP3R1 sensitivity to activation by IP3, using IC4 at a concentration that gives a 1.7-fold increase in IP3R1 sensitivity to IP3. This fold increase in sensitivity is within an experimentally observed range (2-fold) . Fine-tuning of coincidence detection  is preserved.