c-Rel, an NF-κB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation
c-Rel, an NF-κB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation
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DOI：
10.1101/lm.866408
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发表时间：
2008-07-01
影响因子：
2
通讯作者：
Sweatt, J. David
中科院分区：
文献类型：
--
作者：
Ahn, Hyung Jin;Hernandez, Caterina M.;Sweatt, J. David
转录是巩固长期记忆的关键组成部分。然而，相对较少的转录机制已被确定为记忆形成的基因表达调控。在目前的研究中，我们研究了NF-κ B B转录因子家族的一个特定成员c-Rel在记忆巩固过程中的活性。我们发现，情境恐惧条件反射引起海马CA 1区和DG区核c-Rel水平的时间依赖性增加。这些结果表明，c-rel是积极的调节转录记忆巩固。为了确定c-Rel在记忆形成中的功能作用，我们在几个行为任务中表征了c-rel（-/-）小鼠。c-rel（-/-）小鼠在情境恐惧条件化训练后24小时表现出明显的冻结行为缺陷，但在线索恐惧条件化和短期情境恐惧条件化中表现出正常的冻结行为。在一个新的物体识别测试中，野生型同窝小鼠表现出对新物体的明显偏好，但c-rel（-/-）小鼠没有。这些结果表明，c-rel（-/-）小鼠具有受损的海马依赖性记忆形成。为了研究c-Rel在长时程突触可塑性中的作用，评估了c-rel（-/-）小鼠中Schaffer侧支突触处的基线突触传递和长时程增强（LTP）。c-rel（-/-）切片具有正常的基线突触传递，但表现出明显低于野生型同窝仔切片的LTP。总之，我们的研究结果表明，c-Rel是必要的长期突触增强在体外和海马依赖的记忆形成在体内。
Transcription is a critical component for consolidation of long-term memory. However, relatively few transcriptional mechanisms have been identified for the regulation of gene expression in memory formation. In the current study, we investigated the activity of one specific member of the NF-kappa B transcription factor family, c-Rel, during memory consolidation. We found that contextual fear conditioning elicited a time-dependent increase in nuclear c-Rel levels in area CA1 and DG of hippocampus. These results suggest that c-rel is active in regulating transcription during memory consolidation. To identify the functional role of c-Rel in memory formation, we characterized c-rel(-/-) mice in several behavioral tasks. c-rel(-/-) mice displayed significant deficits in freezing behavior 24 h after training for contextual fear conditioning but showed normal freezing behavior in cued fear conditioning and in short-term contextual fear conditioning. In a novel object recognition test, wild-type littermate mice exhibited a significant preference for a novel object, but c-rel(-/-) mice did not. These results indicate that c-rel(-/-) mice have impaired hippocampus-dependent memory formation. To investigate the role of c-Rel in long-term synaptic plasticity, baseline synaptic transmission and long-term potentiation (LTP) at Schaffer collateral synapses in c-rel(-/-) mice was assessed. c-rel(-/-) slices had normal baseline synaptic transmission but exhibited significantly less LTP than did wild-type littermate slices. Together, our results demonstrate that c-Rel is necessary for long-term synaptic potentiation in vitro and hippocampus-dependent memory formation in vivo.