MODULATION OF SYNAPTIC EFFICACY IN FIELD CA1 OF THE RAT HIPPOCAMPUS BY FORSKOLIN
MODULATION OF SYNAPTIC EFFICACY IN FIELD CA1 OF THE RAT HIPPOCAMPUS BY FORSKOLIN
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DOI：
10.1016/0006-8993(92)90803-h
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发表时间：
1992-03-06
期刊：
影响因子：
2.9
通讯作者：
STEVENS, CF
中科院分区：
文献类型：
--
作者：
CHAVEZNORIEGA, LE;STEVENS, CF
cAMP依赖性蛋白激酶（激酶A）的激活最近已被证明可以增强刺激培养的海马锥体神经元中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体引起的反应。 在这里，我们报告的实验结果，旨在确定是否激活cAMP级联增强大鼠海马脑片CA 1区的突触强度。 我们发现，浴应用的直接腺苷酸环化酶激活剂毛喉素（50 μ M）增强场兴奋性突触后电位（EPSP）的斜率和群体尖峰幅度引起的刺激Schaffer/连合传入。 磷酸二酯酶抑制剂和腺苷受体拮抗剂3-异丁基-1-甲基黄嘌呤（IBMX）可增强这种作用。 由毛喉素产生的增强作用在腺苷酸环化酶抑制剂的存在下被抑制，并且不被无活性的毛喉素类似物1，9-二脱氧毛喉素模仿，这表明，腺苷酸环化酶的激活确实介导了毛喉素在CA 1场中的作用。 我们的观察结果支持的想法，细胞内cAMP水平的变化可以调节兴奋性突触的突触效能在哺乳动物海马。
Activation of cAMP-dependent protein kinase (kinase A) has recently been shown to enhance responses evoked by stimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) receptors in cultured hippocampal pyramidal neurons. Here we report results of experiments designed to determine if activation of the cAMP cascade potentiates synaptic strength in field CA1 of rat hippocampal slices. We find that bath application of the direct adenylate cyclase activator forskolin (50-mu-M) enhances the field excitatory postsynaptic potential (EPSP) slope and population spike amplitude evoked by stimulation of Schaffer/commissural afferents. This effect is potentiated by the phosphodiesterase inhibitor and adenosine receptor antagonist 3-isobutyl-1- methylxanthine (IBMX). The enhancement produced by forskolin is suppressed in the presence of adenylate cyclase inhibitors and is not mimicked by the inactive forskolin analogue 1,9-dideoxyforskolin, indicating that, indeed, activation of adenylate cyclase mediates the effects of forskolin in field CA1. Our observations support the idea that changes in intracellular cAMP levels can modulate synaptic efficacy of excitatory glutamatergic synapses in the mammalian hippocampus.