RYR2 and Alzheimer disease: Similarly, presymptomatic 3xTg-AD and TASTPM mice demonstrate exaggerated RyR-evoked Ca2+ release in dendrites and spines associated with altered synaptic plasticity homeostasis and network depression [13]–[16], and early increases in IP3R-mediated Ca2+ release have been found to upregulate pCREB and CAMKIV which are recruited during the induction and expression of synaptic plasticity [17]–[19].