RT Journal Article SR Electronic T1 Long-Term Memory Is Facilitated by cAMP Response Element-Binding Protein Overexpression in the Amygdala JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2404 OP 2412 DO 10.1523/JNEUROSCI.21-07-02404.2001 VO 21 IS 7 A1 Sheena A. Josselyn A1 Chanjun Shi A1 William A. Carlezon, Jr A1 Rachael L. Neve A1 Eric J. Nestler A1 Michael Davis YR 2001 UL http://www.jneurosci.org/content/21/7/2404.abstract AB 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.