Research ArticleNeuroscience

Hippocampal mGluR1-dependent long-term potentiation requires NAADP-mediated acidic store Ca2+ signaling

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Science Signaling  27 Nov 2018:
Vol. 11, Issue 558, eaat9093
DOI: 10.1126/scisignal.aat9093

Acidic Ca2+ stores in synaptic plasticity

Neurotransmitter signaling and neuronal Ca2+ fluxes are critical to learning and memory. Foster et al. found connections between the glutamate receptor mGluR1 and so-called “acidic Ca2+ stores” (Ca2+ stored in acidic organelles) in mouse hippocampal neurons (see the Focus by Patel and Brailoiu). Activation of mGluR1 induced the production of the molecule NAADP, which triggered a cascade of organellar ion channel–mediated Ca2+ release from relatively acidic endosomes and lysosomes to the endoplasmic reticulum. The resulting increase in intracellular Ca2+ depolarized the neurons by paradoxically inhibiting Ca2+-activated SK-type K+ channels, possibly through Ca2+-dependent activation of a phosphatase. These findings identify potential therapeutic targets for patients with neuronal disorders associated with mGluR1 and lysosomal dysfunction.

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