Figure 2.

Schematic of synaptic Ca²⁺ dysregulation in AD. Under normal circumstances (left), impulse mediated increases in presynaptic Ca²⁺ result in neurotransmitter release via a ready releasable vesicular pool. In addition, activation of presynaptic α7nAChRs triggers further Ca²⁺ influx, thus facilitating impulse mediated release, and presynaptic effects may be further increased via presynaptic RyR mediated Ca²⁺-induced-Ca²⁺ release (CICR). In mouse models of AD, although intrinsic cell excitability is not increased, presynaptic RyR mediated CICR may be increased, resulting in increased release probability of glutamate and depletion of vesicle stores. Aβ binding to presynaptic α7nAChRs may result in occlusion of the binding site, with decreased function and eventual decreased presynaptic α7nAChR expression due to endocytosis. In AD, increased ER Ca²⁺ stores, along with increased RyR expression results in increased postsynaptic CICR, which may facilitate stimulus-evoked postsynaptic Ca²⁺ increases.