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 be
en demonstrated that stimuli that induce learning and memory activate CRE-m
ediated gene expression. To address this issue, we used a mouse strain tran
sgenic for a CRE-lac Z reporter to examine the effects of hippocampus-depen
dent learning on CRE-mediated gene expression in the brain. Training for co
ntextual conditioning or passive avoidance led to significant increases in
CRE-dependent gene expression in areas CA1 and CA3 of the hippocampus. Audi
tory cue fear-conditioning, which is amygdala dependent, was associated wit
h increased CRE-mediated gene expression in the amygdala, but not the hippo
campus. These data demonstrate that learning in response to behavioral cond
itioning activates the CRE transcriptional pathway in specific areas of bra
in.