γ-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses
γ-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses
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DOI：
10.1073/pnas.091093998
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发表时间：
2001-04-24
影响因子：
11.1
通讯作者：
Davidson, N
中科院分区：
文献类型：
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作者：
Yu, T;McKinney, S;Davidson, N
cAMP在急性海马脑片中诱导CA 3-CA 1突触的蛋白质合成依赖性长时程增强（LTP）晚期。在此，我们报告cAMP介导的LTP和长期抑郁症（LTD）在单突触CA 3-CA 1细胞对在器官型海马切片培养。在浴中应用膜可渗透的cAMP类似物腺苷3 '，5' -环硫代磷酸，Sp异构体（Sp-cAMPS）后，突触传递增强至少2小时。与先前的发现一致，LTP的晚期需要cAMP依赖性蛋白激酶A和蛋白质合成的激活。cAMP诱导的LTP也有一个早期阶段，早期阶段依赖于蛋白激酶A，但与晚期阶段相反，不需要蛋白质合成，此外，cAMP诱导的LTP与配对脉冲易化的减少有关，这表明可能涉及突触前修饰。此外，我们发现Sp-cAMPS诱导LTD在切片预处理与印防己毒素。一种γ-氨基丁酸A型（GABA（A））受体拮抗剂。这种LTD依赖于蛋白质合成和蛋白磷酸酶，并伴随着突触传递失败率的增加。这些结果表明，GABA（A）受体可调节cAMP对突触传递的影响，从而决定突触可塑性的方向。
cAMP induces a protein-synthesis-dependent late phase of longterm potentiation (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 cell pairs in organotypic hippocampal slice cultures. After bath application of the membrane-permeable cAMP analog adenosine 3 ' ,5 ' -cyclic monophosphorothioate, Sp isomer (Sp-cAMPS), synaptic transmission was enhanced for at least 2 h, Consistent with previous findings, the late phase of LTP requires activation of cAMP-dependent protein kinase A and protein synthesis. There is also an early phase of LTP induced by cAMP; the early phase depends on protein kinase A but, in contrast to the later phase, does not require protein synthesis, in addition, the cAMP-induced LTP is associated with a reduction of paired-pulse facilitation, suggesting that presynaptic modification may be involved. Furthermore, we found that Sp-cAMPS induced LTD in slices pretreated with picrotoxin. a gamma -aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends on protein synthesis and protein phosphatase(s) and is accompanied by an increased ratio of failed synaptic transmission, These results suggest that GABA(A) receptors can modulate the effect of cAMP on synaptic transmission and thus determine the direction of synaptic plasticity.