Nguyen P V, Kandel E R
Howard Hughes Medical Institute, New York, New York 10032, USA.
J Neurosci. 1996 May 15;16(10):3189-98. doi: 10.1523/JNEUROSCI.16-10-03189.1996.
Memory storage consists of a short-term phase that is independent of new protein synthesis and a long-term phase that requires the synthesis of new proteins and RNA. A cellular representation of these two phases has been demonstrated recently for long-term potentiation (LTP) in both the Schaffer collateral and the mossy fibers of the hippocampus, a structure widely thought to contribute to memory consolidation. By contrast, much less information is available about the medial perforant pathway (MPP), one of the major inputs to the hippocampus. We found that both a short-lasting and a long-lasting potentiation (L-LTP) can be induced in the MPP of rat hippocampal slices by applying repeated tetanization in reduced levels of magnesium. This potentiation was dependent on the activation of NMDA receptors. The early, transient phase of LTP in the MPP did not require either protein or RNA synthesis, and it was independent of protein kinase A activation. By contrast, L-LTP required the synthesis of proteins and RNA, and was selectively blocked by inhibitors of cAMP-dependent protein kinase (PKA). Forskolin, an adenylate cyclase activator, also induced a L-LTP that was attenuated by inhibition of transcription. Our results demonstrate that, like LTP in the Schaffer collateral and mossy fiber pathways, MPP LTP also consists of a late phase that is dependent on protein and RNA synthesis and PKA activity. Thus, cAMP-mediated transcription appears to be a common mechanism for the late form of LTP in all three pathways within the hippocampus.
记忆存储包括一个独立于新蛋白质合成的短期阶段和一个需要合成新蛋白质及RNA的长期阶段。最近在海马体的沙费尔侧支和苔藓纤维（一个被广泛认为对记忆巩固有作用的结构）中，已证明了这两个阶段在长时程增强（LTP）中的细胞表现。相比之下，关于海马体的主要输入之一——内侧穿通通路（MPP）的信息则少得多。我们发现，通过在降低的镁水平下进行重复强直刺激，可以在大鼠海马切片的MPP中诱导出短暂的和持久的增强（L-LTP）。这种增强依赖于NMDA受体的激活。MPP中LTP的早期短暂阶段既不需要蛋白质合成也不需要RNA合成，并且它独立于蛋白激酶A的激活。相比之下，L-LTP需要蛋白质和RNA的合成，并且被环磷酸腺苷依赖性蛋白激酶（PKA）抑制剂选择性阻断。腺苷酸环化酶激活剂福斯可林也诱导出一种L-LTP，这种L-LTP会因转录抑制而减弱。我们的结果表明，与沙费尔侧支和苔藓纤维通路中的LTP一样，MPP LTP也包括一个依赖于蛋白质和RNA合成以及PKA活性的晚期阶段。因此，cAMP介导的转录似乎是海马体内所有这三条通路中LTP晚期形式的共同机制。
