ACTIVITY-DEPENDENT LONG-TERM ENHANCEMENT OF TRANSMITTER RELEASE BY PRESYNAPTIC 3',5'-CYCLIC GMP IN CULTURED HIPPOCAMPAL-NEURONS
ACTIVITY-DEPENDENT LONG-TERM ENHANCEMENT OF TRANSMITTER RELEASE BY PRESYNAPTIC 3',5'-CYCLIC GMP IN CULTURED HIPPOCAMPAL-NEURONS
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DOI：
10.1038/376074a0
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发表时间：
1995-07-06
期刊：
影响因子：
64.8
通讯作者：
HAWKINS, RD
中科院分区：
文献类型：
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作者：
ARANCIO, O;KANDEL, ER;HAWKINS, RD
海马体中的长期增强（LTP）是一种突触可塑性，被认为与学习和记忆有关(1)。一些证据表明，LTP涉及3',5'-环GMP (cGMP)，可能是一种或多种逆行信使的活性依赖性突触前效应物（参考文献2-12，但参见参考文献13）。然而，先前的结果也与cGMP的突触后效应一致。这很难在海马体切片中进行测试，但在分离细胞培养中可能进行更严格的测试（14-17）。因此，我们开发了一种可靠的方法，在培养的海马锥体神经元之间的突触上产生n -甲基-d -天冬氨酸（NMDA）受体依赖的LTP。我们报告说，关酰环化酶抑制剂或cgmp依赖性蛋白激酶抑制剂通过破伤风刺激或低频刺激与突触后去极化配对来阻断增强。相反，将8-Br-cGMP应用到突触前神经元中或将cGMP注射到突触前神经元中，会产生活动依赖性的持久增强。cGMP的增强涉及递质释放的增加，这在一定程度上与突触前动作电位的变化无关。这些结果支持cGMP在LTP中的突触前作用。
LONG-TERM potentiation (LTP) in hippocampus is a type of synaptic plasticity that is thought to be involved in learning and memory(1). Several lines of evidence suggest that LTP involves 3',5'-cyclic GMP (cGMP), perhaps as an activity-dependent presynaptic effector of one or more retrograde messengers (refs 2-12, but see ref, 13). However, previous results are also consistent with postsynaptic effects of cGMP. This is difficult to test in hippocampal slices, but more rigorous tests are possible in dissociated cell culture(14-17). We have therefore developed a reliable method for producing N-methyl-D-aspartate (NMDA) receptor-dependent LTP at synapses between individual hippocampal pyramidal neurons in culture, We report that inhibitors of guanylyl cyclase or of cGMP-dependent protein kinase block potentiation by either tetanic stimulation or low-frequency stimulation paired with postsynaptic depolarization. Conversely, application of 8-Br-cGMP to the bath or injection of cGMP into the presynaptic neuron produces activity-dependent long-lasting potentiation, The potentiation by cGMP involves an increase in transmitter release that is in part independent of changes in the presynaptic action potential. These results support a presynaptic role for cGMP in LTP.