biostudies-literatureWu BNINDS NIH HHS15091-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3773738biostudies-literatureUnknown110(37)Presenilin (PS) plays a central role in the pathogenesis of Alzheimer's disease, and loss of PS causes progressive memory impairment and age-related neurodegeneration in the mouse cerebral cortex. In hippocampal neurons, PS is essential for neurotransmitter release, NMDA receptor-mediated responses, and long-term potentiation. PS is also involved in the regulation of calcium homeostasis, although the precise site of its action is less clear. Here we investigate the mechanism by which PS regulates synaptic function and calcium homeostasis using acute hippocampal slices from PS conditional knockout mice and primary cultured postnatal hippocampal neurons, in which PS is inducibly inactivated. Using two different calcium probes, Fura-2 and Mag-Fura-2, we found that inactivation of PS in primarProceedings of the National Academy of Sciences of the United States of AmericaPresenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons.PMC3773738RF1 NS041783R01 NS041783R01 NS041779Lai FAShen JWu BYamaguchi HfalsePresenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons.Presenilin (PS) plays a central role in the pathogenesis of Alzheimer's disease, and loss of PS causes progressive memory impairment and age-related neurodegeneration in the mouse cerebral cortex. In hippocampal neurons, PS is essential for neurotransmitter release, NMDA receptor-mediated responses, and long-term potentiation. PS is also involved in the regulation of calcium homeostasis, although the precise site of its action is less clear. Here we investigate the mechanism by which PS regulates synaptic function and calcium homeostasis using acute hippocampal slices from PS conditional knockout mice and primary cultured postnatal hippocampal neurons, in which PS is inducibly inactivated. Using two different calcium probes, Fura-2 and Mag-Fura-2, we found that inactivation of PS in primar2013-01-01T00:00:00Z2013 Sep2025-04-26T13:54:32.028Z2019-03-27T01:16:02ZS-EPMC37737382391838610.1073/pnas.1304171110