Arancio O, Kandel E R, Hawkins R D
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York 10032, USA.
Nature. 1995 Jul 6;376(6535):74-80. doi: 10.1038/376074a0.
Long-term potentiation (LTP) in hippocampus is a type of synaptic plasticity that is thought to be involved in learning and memory. 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. 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.
海马体中的长时程增强效应（LTP）是一种突触可塑性，被认为与学习和记忆有关。多条证据表明，LTP涉及3',5'-环鸟苷酸（cGMP），可能作为一种或多种逆行信使的活动依赖性突触前效应器（参考文献2 - 12，但见参考文献13）。然而，先前的结果也与cGMP的突触后效应一致。这在海马体切片中很难进行测试，但在解离细胞培养中可以进行更严格的测试。因此，我们开发了一种可靠的方法，用于在培养的单个海马体锥体神经元之间的突触处产生N-甲基-D-天冬氨酸（NMDA）受体依赖性LTP。我们报告称，鸟苷酸环化酶抑制剂或cGMP依赖性蛋白激酶抑制剂可阻断强直刺激或与突触后去极化配对的低频刺激所引起的增强效应。相反，将8-溴-cGMP应用于浴液或向突触前神经元注射cGMP会产生活动依赖性的持久增强效应。cGMP引起的增强效应涉及递质释放的增加，这部分独立于突触前动作电位的变化。这些结果支持了cGMP在LTP中的突触前作用。
