French P J, O'Connor V, Jones M W, Davis S, Errington M L, Voss K, Truchet B, Wotjak C, Stean T, Doyère V, Maroun M, Laroche S, Bliss T V
National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Eur J Neurosci. 2001 Mar;13(5):968-76. doi: 10.1046/j.0953-816x.2001.01467.x.
It is not known whether NMDA receptor-dependent long-term potentiation (LTP) is mediated by similar molecular mechanisms in different hippocampal areas. To address this question we have investigated changes in immediate early gene and protein expression in two hippocampal subfields following the induction of LTP in vivo and in vitro. In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the immediate early genes (IEGs) Zif268, Arc and Homer. The increase in Zif268 mRNA was accompanied by an increase in protein expression. In contrast, we were unable to detect modulation of the IEGs Zif268, Arc, Homer and HB-GAM following induction of LTP by high-frequency stimulation of the commissural projection to CA1 pyramidal cells in vivo. In this pathway, we also failed to detect modulation of Zif268 protein levels. Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli. When LTP was induced in vitro neither CA1 pyramidal cells nor granule cells showed an increase in Zif268, Arc or Homer mRNA. However, in the slice preparation, granule cells have a different transcriptional state as basal IEG levels are elevated. These results establish the existence of subfield-specific transcriptional responses to LTP-inducing stimulation in the hippocampus of the intact animal, and demonstrate that in area CA1-enhanced transcription of Zif268, Arc and Homer is not required for the induction of late LTP.
尚不清楚N-甲基-D-天冬氨酸（NMDA）受体依赖性长时程增强（LTP）在不同海马区域是否由相似的分子机制介导。为解决这一问题，我们研究了体内和体外诱导LTP后，两个海马亚区即刻早期基因和蛋白表达的变化。在齿状回颗粒细胞中，通过强直刺激穿通通路在体内诱导LTP后，即刻早期基因（IEGs）Zif268、Arc和Homer被强烈诱导。Zif268 mRNA的增加伴随着蛋白表达的增加。相比之下，在体内通过高频刺激连合投射至CA1锥体细胞诱导LTP后，我们未能检测到IEGs Zif268、Arc、Homer和HB-GAM的调节。在这条通路中，我们也未能检测到Zif268蛋白水平的调节。电击诱发最大癫痫发作后，CA1锥体细胞中的Zif268、Arc和Homer可被调节约两倍，这表明对电刺激具有潜在反应性。当在体外诱导LTP时，CA1锥体细胞和颗粒细胞均未显示Zif268、Arc或Homer mRNA增加。然而，在脑片制备中，颗粒细胞具有不同的转录状态，因为基础IEG水平升高。这些结果证实了完整动物海马中存在对LTP诱导刺激的亚区特异性转录反应，并表明在CA1区，Zif268、Arc和Homer的增强转录对于晚期LTP的诱导并非必需。
