RYR2 and Alzheimer disease: Our previous studies in pre-symptomatic 3xTg-AD mice demonstrated disruptions in Ca2+-regulated synaptic transmission and plasticity mechanisms, where the RyRs are a dominant and aberrant modulator of basal synaptic transmission and presynaptic plasticity, and acute RyR inhibition in vitro results in a shift towards synaptic depression [13], [16].