Evidence of a role for cyclic ADP-ribose in long-term syntaptic depression in hippocampus

摘要

Ca~2+ released from presynaptic and postsyn- aptic intracellular stores plays important roles in activity- dependent synaptic plasticity, including long-term depres sion (LTD) of synaptic strength. At Schaffer collateral-CAI syn- apses in the hippocampus, Presynaptic ryanodine receptor- gated stores appear to mobilize some of the Caz+ 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 cANPR concentration in hip- pocampal slices in vitro, and that blockade of cGMP. dependent protein kinase, cADPR receptors, or ryanodine- sensitive Caz+ storcs each prevent the induction of LTD at Schaffer collateral-CAI synapses. A lack of effect of postsyn- aptic infusion of either cADPR antagonist indicates a prob- able Presynaptic site of action.