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. Author manuscript; available in PMC: 2012 Nov 1.
Published in final edited form as: Trends Mol Med. 2011 Jul 26;17(11):617–624. doi: 10.1016/j.molmed.2011.06.002

Figure 3. Models depicting how presenilins regulate synaptic function.

Figure 3

Upon depolarization, intracellular calcium levels are elevated due to calcium influx through voltage-gated calcium channels (VGCC), store-operated calcium channels (SOC), and calcium induced calcium release (CICR) from intracellular endoplasmic reticulum (ER) stores that is mediated through the ryanodine (RyR) and the inositol-1,4,5-triphosphate receptors (IP3R). Cytosolic calcium into the ER lumen is mediated through sarco-ER calcium ATPases (SERCAs) pumps. Inactivation of presynaptic presenilins in FB-PS cDKO and CA3-PS cDKO mice alters presynaptic release machinery through its control of calcium release from RyR in the ER thus reducing CICR. The reduction in calcium impairs the probability of neurotransmitter release (Pr), pair-pulse facilitation (PPF) and frequency facilitation (FF) which causes postsynaptic LTP impairments. In addition, inactivation of presynaptic and postsynaptic presenilins in FB-PS cDKO mice decreases NMDAR functions thus contributing to LTP deficits. Meanwhile, inactivation of postsynaptic presenilins in CA1-PS cDKO mice did not display any changes in short- and long-term plasticity.