Josselyn S A, Shi C, Carlezon W A, Neve R L, Nestler E J, Davis M
Department of Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.
J Neurosci. 2001 Apr 1;21(7):2404-12. doi: 10.1523/JNEUROSCI.21-07-02404.2001.
At least two temporally and mechanistically distinct forms of memory are conserved across many species: short-term memory that persists minutes to hours after training and long-term memory (LTM) that persists days or longer. In general, repeated training trials presented with intervening rest intervals (spaced training) is more effective than massed training (the same number of training trials presented with no or short intervening rest intervals) in producing LTM. LTM requires de novo protein synthesis, and cAMP response element-binding protein (CREB) may be one of the transcription factors regulating the synthesis of new proteins necessary for the formation of LTM. Here we show that rats given massed fear conditioning training show no or weak LTM, as measured by fear-potentiated startle, compared with rats given the same amount of training but presented in a spaced manner. Increasing CREB levels specifically in the basolateral amygdala via viral vector-mediated gene transfer significantly increases LTM after massed fear training. The enhancing effect of CREB overexpression on LTM formation is shown to be specific in terms of biochemistry, anatomy, time course, and the training procedure used. These results suggest that CREB activity in the amygdala serves as a molecular switch for the formation of LTM in fear conditioning.
训练后持续数分钟至数小时的短期记忆以及持续数天或更长时间的长期记忆（LTM）。一般来说，在产生长期记忆方面，间隔休息时间进行重复训练试验（间隔训练）比集中训练（相同次数的训练试验，中间无休息间隔或休息间隔很短）更有效。长期记忆需要从头合成蛋白质，而环磷酸腺苷反应元件结合蛋白（CREB）可能是调节长期记忆形成所需新蛋白质合成的转录因子之一。在这里我们表明，与接受相同训练量但以间隔方式进行训练的大鼠相比，接受集中恐惧条件训练的大鼠通过恐惧增强惊吓反应测量显示没有或只有微弱的长期记忆。通过病毒载体介导的基因转移特异性增加基底外侧杏仁核中的CREB水平，在集中恐惧训练后显著增加长期记忆。CREB过表达对长期记忆形成的增强作用在生物化学、解剖学、时间进程和所使用的训练程序方面都具有特异性。这些结果表明，杏仁核中的CREB活性是恐惧条件反射中长期记忆形成的分子开关。
