Nayak A, Zastrow D J, Lickteig R, Zahniser N R, Browning M D
Neuroscience Program, University of Colorado Health Sciences Center, Denver 80262, USA.
Nature. 1998 Aug 13;394(6694):680-3. doi: 10.1038/29305.
Long-term potentiation (LTP) is a form of synaptic plasticity that has been extensively studied as a putative mechanism underlying learning and memory. A late phase of LTP occurring 3-5 hours after stimulation and depending on transcription, protein synthesis and cyclic-AMP-dependent protein kinase (protein kinase A, or PKA) has been described, but it is not known whether transcription of presynaptic and/or postsynaptic genes is required to support late-phase LTP. Here we show that late-phase LTP can be obtained in rat hippocampal CA1 mini-slices in which the cell bodies of presynaptic Schaffer collateral/commissural fibres are removed. Thus, transcription of presynaptic genes is not necessary to support maintenance of late-phase LTP. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor is the predominant mediator of the ionotropic response to synaptically released glutamate in the hippocampus and it has been implicated in LTP maintenance. We find that synthesis of AMPA receptor subunits is increased three hours after LTP induction: this effect on the synthesis of the AMPA receptor is blocked by inhibitors of PKA and of transcription. Our results support the idea of a postsynaptic mechanism maintaining late-phase LTP, in which AMPA receptor synthesis is increased as a result of PKA-dependent gene transcription.
长时程增强（LTP）是一种突触可塑性形式，作为学习和记忆的潜在机制已被广泛研究。已经描述了LTP的一个晚期阶段，它发生在刺激后3 - 5小时，依赖于转录、蛋白质合成和环磷酸腺苷依赖性蛋白激酶（蛋白激酶A，或PKA），但尚不清楚是否需要突触前和/或突触后基因的转录来支持晚期LTP。在这里，我们表明，在去除突触前谢弗侧支/联合纤维细胞体的大鼠海马CA1微型切片中可以获得晚期LTP。因此，突触前基因的转录对于支持晚期LTP的维持不是必需的。AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体是海马中对突触释放谷氨酸的离子otropic反应的主要介质，并且它与LTP维持有关。我们发现，LTP诱导后三小时，AMPA受体亚基的合成增加：对AMPA受体合成的这种影响被PKA和转录抑制剂阻断。我们的结果支持了一种维持晚期LTP的突触后机制的观点，其中由于PKA依赖性基因转录，AMPA受体合成增加。
