SOMATODENDRITIC EXPRESSION OF AN IMMEDIATE-EARLY GENE IS REGULATED BY SYNAPTIC ACTIVITY
SOMATODENDRITIC EXPRESSION OF AN IMMEDIATE-EARLY GENE IS REGULATED BY SYNAPTIC ACTIVITY
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DOI：
10.1073/pnas.92.12.5734
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发表时间：
1995-06-06
影响因子：
11.1
通讯作者：
KUHL, D
中科院分区：
文献类型：
--
作者：
LINK, W;KONIETZKO, U;KUHL, D
基因表达的跨突触激活与神经系统长期的可塑性适应有关，为了研究突触活动诱导的分子程序，我们利用分子克隆技术鉴定了一个在大脑中快速诱导的即刻早期基因。我们在此报道了该基因的全部核苷酸序列，它编码一个396个氨基酸的开放阅读框，在海马区，结构性表达很低。大脑皮质的基础表达水平很高，但可以通过阻断N-甲基-D-天冬氨酸受体显着降低。相比之下，惊厥发作引起的突触活动增加了大脑皮层和海马神经元中的mRNA水平。高频刺激穿支通路导致同侧齿状回颗粒细胞的长时程增强和空间受限的mRNA水平的显著增加，转录本定位于胞体和颗粒细胞的树突，转录本的树突定位提供了在激活的突触后位置局部合成蛋白质的可能性，并可能在长期的可塑性事件中为突触特异性修饰奠定基础。
Trans-synaptic activation of gene expression is linked to long-term plastic adaptations in the nervous system, To examine the molecular program induced by synaptic activity, we have employed molecular cloning techniques to identify an immediate early gene that is rapidly induced in the brain. We here report the entire nucleotide sequence of the cDNA, which encodes an open reading frame of 396 amino acids, Within the hippocampus, constitutive expression was low. Basal levels of expression in the cortex were high but can be markedly reduced by blockade of N-methyl-D-aspartate receptors. By contrast, synaptic activity induced by convulsive seizures increased mRNA levels in neurons of the cortex and hippocampus. High-frequency stimulation of the perforant path resulted in long-term potentiation and a spatially confined dramatic increase in the level of mRNA in the granule cells of the ipsilateral dentate gyrus, Transcripts were localized to the soma and to the dendrites of the granule cells, The dendritic localization of the transcripts offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events.