Recent studies suggest that the CREB-CRE transcriptional pathway is pivotal in the formation of some types of long-term memory. However, it has not been demonstrated that stimuli that induce learning and memory activate CRE-mediated gene expression. To address this issue, we used a mouse strain transgenic for a CRE-lac Z reporter to examine the effects of hippocampus-dependent learning on CRE-mediated gene expression in the brain. Training for contextual conditioning or pas-sive avoidance led to significant increases in CRE-dependent gene expression in areas CA1 and CA3 of the hippocampus. Auditory cue fear-conditioning, which is amygdala dependent, was associated with increased CRE-mediated gene expression in the amygdala, but not the hippocampus. These data demonstrate that learning in response to behavioral conditioning activates the CRE transcriptional pathway in specific areas of brain.
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