DEFICIENT LONG-TERM-MEMORY IN MICE WITH A TARGETED MUTATION OF THE CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN
DEFICIENT LONG-TERM-MEMORY IN MICE WITH A TARGETED MUTATION OF THE CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN
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DOI：
10.1016/0092-8674(94)90400-6
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发表时间：
1994-10-07
期刊：
影响因子：
64.5
通讯作者：
SILVA, AJ
中科院分区：
文献类型：
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作者：
BOURTCHULADZE, R;FRENGUELLI, B;SILVA, AJ
cAMP反应元件结合蛋白（CREB）参与激活长期易化所需的蛋白质合成，长期易化是记忆障碍的细胞模型。我们对恐惧条件反射和水迷宫的研究表明，有针对性地破坏CREB α和δ亚型的小鼠在长期记忆方面存在严重缺陷。相比之下，短期记忆，持续30至60分钟，是正常的。与声称长时程增强（LTP）在记忆中的作用的模型一致，来自CREB突变体的海马切片中的LTP在强直刺激后90分钟衰减至基线。然而，成对脉冲易化和强直后增强是正常的。这些结果暗示CREB依赖的转录在哺乳动物的长期记忆。
The cAMP-responsive element-binding protein (CREB) has been implicated in the activation of protein synthesis required for long-term facilitation, a cellular model of memory in Aplysia. Our studies with fear conditioning and with the water maze show that mice with a targeted disruption of the alpha and delta isoforms of CREB are profoundly deficient in long-term memory. In contrast, short-term memory, lasting between 30 and 60 min, is normal. Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation. However, paired-pulse facilitation and posttetanic potentiation are normal. These results implicate CREB-dependent transcription in mammalian long-term memory.