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The DNA binding of CREB is mediated via its basic leucine zipper domain (bZIP domain) as depicted in the image. doi: 10.1126/science.1166859, Martin, L. J. CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus.

Inducible forebrain-specific ablation of the transcription factor creb during adulthood induces anxiety but no spatial/contextual learning deficits. Neuron 34, 447–462. cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb.

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A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos.  |  doi: 10.1038/4151030a, Vo, N., Klein, M. E., Varlamova, O., Keller, D. M., Yamamoto, T., Goodman, R. H., et al. 4, 1313–1317. CREB also has an important role in the development of drug addiction and even more so in psychological dependence. One emergent hypothesis regarding the prevention of consolidation of STM into LTM involves the inhibition of proteins or transcription factors. Two groups used rolipram, an inhibitor of phosphodiesterase-4-enhancing CREB signaling, (Nakagawa et al., 2002b; Fujioka et al., 2004) to examine CREB function in vivo; they reported an increase in different parameters of adult neurogenesis in the SGZ, including a higher survival rate of new neurons, more precursor cell proliferation, and enhanced neurite outgrowth and dendritic branching (Merz et al., 2011). The role of CREB signaling in neuronal activation and during survival stages of neurogenesis is better understood than its effects on cell migration and proliferation (Dworkin and Mantamadiotis, 2010). If CBP/p300 does not cluster at a gene promoter after CREB phosphorylation, the gene remains transcriptionally silent (Merz et al., 2011). The upregulation of BDNF and CREB activity synergistically improves LTM formation (Suzuki et al., 2011). Regulation of the CREB signaling cascade in the visual cortex by visual experience and neuronal activity. Sci. (2010). Stem Cells 27, 1347–1357. Bull.

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