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J Neurosci. 2008 Feb 20;28(8):1970-6. doi: 10.1523/JNEUROSCI.3848-07.2008.

cAMP response element-binding protein 1 feedback loop is necessary for consolidation of long-term synaptic facilitation in Aplysia.

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Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.


The transcription factor cAMP response element (CRE)-binding protein (CREB) plays an essential role in the induction of many forms of long-term synaptic plasticity. Levels of CREB1, the Aplysia homolog of CREB, show sustained elevations for several hours after the induction of long-term synaptic facilitation (LTF). Furthermore, CREB1 binds to the promoter of its own gene. These results suggest the existence of a CREB1-positive feedback loop that contributes to the consolidation of LTF. In the present study, we provide a detailed, quantitative characterization of the dynamics of CREB1 mRNA and protein as well as CREB1 phosphorylation after LTF induction. Injections of CRE oligonucleotides prevented the increase in CREB1 in response to 5-HT, corroborating the existence of the CREB1 feedback loop. This loop probably sustains CRE-dependent gene transcription, which remains elevated for at least 12 h after LTF induction. LTF is blocked by injection of CREB1 antibody after the induction phase, suggesting that the CREB1-positive feedback is required for consolidation of LTF.

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