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病毒介导的海马神经元中组成型活性形式的CREB表达可增强记忆。

Viral-mediated expression of a constitutively active form of CREB in hippocampal neurons increases memory.

作者信息

Restivo Leonardo, Tafi Elisiana, Ammassari-Teule Martine, Marie Hélène

机构信息

Institute for Neuroscience, CNR, IRCCS S Lucia Foundation, Rome, Italy.

出版信息

Hippocampus. 2009 Mar;19(3):228-34. doi: 10.1002/hipo.20527.

DOI:10.1002/hipo.20527
PMID:19004015
Abstract

Synaptic activity-dependent phosphorylation of the transcription factor cAMP response element binding protein (CREB) leads to CREB-dependent gene transcription, a process thought to underlie long-term hippocampal synaptic plasticity and memory formation. We previously reported that increasing CREB activity in glutamatergic neurons enhances synaptic plasticity and neuronal excitability. Whether these modifications are sufficient to promote hippocampal-dependent memory formation was not determined. Here, we provide direct evidence that a brief increase in CREB-dependent transcription in either CA1 or DG neurons, using in vivo viral vectors, is sufficient to boost memory for contextual representations, as tested in the contextual fear conditioning task, without affecting motor, pain, or anxiety behaviors.

摘要

转录因子环磷酸腺苷反应元件结合蛋白(CREB)的突触活动依赖性磷酸化会导致CREB依赖性基因转录,这一过程被认为是长期海马体突触可塑性和记忆形成的基础。我们之前报道过,增强谷氨酸能神经元中的CREB活性可增强突触可塑性和神经元兴奋性。但这些改变是否足以促进海马体依赖性记忆形成尚未确定。在此,我们提供了直接证据,即使用体内病毒载体短暂增加CA1或齿状回(DG)神经元中CREB依赖性转录,就足以增强情境记忆,这在情境恐惧条件反射任务中得到了验证,且不会影响运动、疼痛或焦虑行为。

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