Proceedings of the National Academy of Sciences · 1999 · 96 citations · 20 references
Life SciencesNeurobiologyNeuroscienceCell SignalingSignal TransductionSynaptic PlasticityCalcium SignalingIntracellular Calcium SignalingLong-term DepressionSynaptic SignalingSynaptic Strength RegulationSynaptic TransmissionActivity-dependent Synaptic DepressionCalcium Signaling In NeuronsCalcium Signaling In SynapsesHippocampal Long-term DepressionRyanodine Receptor ActivationRyanodine Receptor SignalingRyanodine ReceptorsSchaffer Collateral Pathway
Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action.
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Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Rosel M. Mulkey, Shogo Endo, Shirish Shenolikar et al. · Nature · 1994 · 1.1K citations