Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus
Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus
复制标题
DOI：
10.1073/pnas.96.7.4061
复制
发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Stanton, PK
中科院分区：
文献类型：
--
作者：
Reyes-Harde, M;Empson, R;Stanton, PK
突触前和突触后细胞内储存释放的 Ca2+ 在活动依赖性突触可塑性中发挥重要作用，包括突触强度的长期抑制 (LTD)。在海马的 Schaffer 侧支 CA1 突触处，突触前兰尼碱受体门控储存似乎动员了一些诱导 LTD 所需的 Ca2+。环状 ADP-核糖 (cADPR) 最近被提议作为海胆卵和几种哺乳动物细胞类型中兰尼碱受体的内源性激活剂。在这里，我们提供了cADPR介导的信号通路在诱导LTD中发挥关键作用的证据，我们表明cGMP的生化产生增加了体外海马切片中的cADPR浓度，并且阻断cGMP依赖的蛋白激酶、cADPR受体或兰尼碱敏感的Ca2+储存可各自阻止Schaffer侧支CA1处LTD的诱导 突触。任一 cADPR 拮抗剂突触后输注缺乏作用表明可能存在突触前作用位点。
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.