Generation of dendritic Ca2+ oscillations as a consequence of altered ryanodine receptor function in AD neurons

Ryanodine receptor (RyR)-mediated Ca2+ dysregulation is associated with Alzheimer's disease (AD) neuropathology. Using 2-photon Ca2+ imaging and patch clamp recordings in brain slice preparations from young 3xTg-AD and NonTg control mice, we recently demonstrated that RyR-mediated Ca2+-induced Ca2+ release (CICR) is substantially increased within dendrites from AD neurons, such that synaptic stimulation alone is sufficient to generate aberrant CICR. We also observed supra-additive Ca2+ release upon coincident RyR activation with synaptic stimulation in 3xTg-AD mice. Here, we describe an additional observed phenomenon: generation of patterned Ca2+ oscillations in the spines and dendrites from AD neurons upon coincident RyR and synaptic stimulation. As the temporal entrainment of Ca2+ signals influences many downstream cellular and synaptic functions, these abnormal oscillatory patterns may be associated with the structural and functional breakdown of synapses in AD.