Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins
Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins
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DOI：
10.1016/s0896-6273(03)00501-4
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发表时间：
2003-08-14
期刊：
影响因子：
16.2
通讯作者：
Kandel, ER
中科院分区：
文献类型：
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作者：
Chen, A;Muzzio, IA;Kandel, ER
为了研究C/EBP相关转录因子在长期突触可塑性和记忆存储中的作用，我们利用四环素调控系统，在小鼠的前脑表达了一个广泛的显性-负性C/EBP抑制物(EGFP-Azip)，它优先与C/EBP的几种抑制亚型相互作用。EGFP-AZIP还降低ATF4的表达，ATF4是C/EBP转录因子家族中的一个遥远成员，与海兔记忆抑制基因ApCREB-2同源。与转录抑制限制的解除一致，我们发现EGFP-Azip转基因小鼠海马区基因转录模式增加，基于海马区的空间记忆和LTP都有可逆性增强。这些结果表明，C/EBP家族中的几种蛋白质，包括ATF4(CREB-2)，可以限制长期突触的变化和记忆的形成。这种抑制的解除降低了小鼠海马区依赖的长期突触增强和记忆存储的阈值。
To examine the role of C/EBP-related transcription factors in long-term synaptic plasticity and memory storage, we have used the tetracycline-regulated system and expressed in the forebrain of mice a broad dominant-negative inhibitor of C/EBP (EGFP-AZIP), which preferentially interacts with several inhibiting isoforms of C/EBP. EGFP-AZIP also reduces the expression of ATF4, a distant member of the C/EBP family of transcription factors that is homologous to the Aplysia memory suppressor gene ApCREB-2. Consistent with the removal of inhibitory constraints on transcription, we find an increase in the pattern of gene transcripts in the hippocampus of EGFP-AZIP transgenic mice and both a reversibly enhanced hippocampal-based spatial memory and LTP. These results suggest that several proteins within the C/EBP family including ATF4 (CREB-2) act to constrain long-term synaptic changes and memory formation. Relief of this inhibition lowers the threshold for hippocampal-dependent long-term synaptic potentiation and memory storage in mice.