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Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning

Abstract

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 passive 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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Figure 1: Contextual conditioning and CRE-mediated gene expression in mice transgenic for CRE-Lac Z.
Figure 2: Effect of contextual conditioning on pCREB levels in area CA1 of the hippocampus.
Figure 3: Auditory-cue conditioning and CRE-mediated gene expression in mice transgenic for CRE-Lac Z.
Figure 4: CRE-mediated gene expression in the basolateral amygdala of fear-conditioned mice.
Figure 5: Passive avoidance learning and CRE-mediated gene expression in the hippocampus.

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Acknowledgements

We thank Lauren Baker and Zhengui Xia for reading the manuscript. Microscopy and image analysis was done in the W. M. Keck Center for Neural Signaling, University of Washington. This research was supported by National Institutes of Health grant NS 20498.

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Correspondence to Daniel R. Storm.

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Impey, S., Smith, D., Obrietan, K. et al. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1, 595–601 (1998). https://doi.org/10.1038/2830

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