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Neurosci. The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Biol. This family belongs to the superfamily of basic region/leucine zipper (bZIP) transcriptional regulators, and all its members mediate cAMP-responsive transcription. 100, 433–442. (2015). CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects. Josselyn, S. A., Shi, C., Carlezon, W. A. Jr., Neve, R. L., Nestler, E. J., and Davis, M. (2001). doi: 10.3410/f.1029191.343602, Vogt, M. A., Inta, D., Luoni, A., Elkin, H., Pfeiffer, N., Riva, M. A., et al. [4], Michael Greenberg first demonstrated the role of CREB in the mammalian circadian clock in 1993 through a series of experiments that correlated phase-specific light pulses with CREB phosphorylation. 31, 8786–8802. Nat. Neurogenic hypothesis for CREB’s role in the regulation of memory. Mol. CREB’s affects memory consolidation through its regulation of adult hippocampal neurogenesis (AHN), which mainly occurs in the hippocampal subgranular zone (SGZ) of the dentate gyrus (DG). 368:20120535. doi: 10.1098/rstb.2012.0535, Altman, J., and Das, G. D. (1965). A dominant repressor of cyclic adenosine 3′,5′-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. In this regard, evidence for this hypothesis is crucial to design follow-up studies. Different genetic models used for the study of CREB function were analyzed. With regard to the former, enhanced CREB signaling has been widely described to promote newborn neuron survival, precursor cell proliferation, and neurite outgrowth, and dendritic branching (Giachino et al., 2005; Merz et al., 2011). Nature 345, 718–721.  |  (2009). The cAMP responsive element binding protein (CREB) is a nuclear protein that modulates the transcription of genes with cAMP responsive elements in their promoters. doi: 10.1016/s0169-328x(02)00550-8, Kim, J., Kwon, J. T., Kim, H. S., and Han, J. H. (2013). Progress in understanding the cellular processes regulating gene expression networks in cognition is relevant to develop therapeutic interventions for age-related cognitive disorders. Overall, the study results suggested that CREB isoforms play a role in experience-dependent plasticity in the adult neocortex (Glazewski et al., 1999). The existence of “adult neurogenesis” in mammals was first confirmed 50 years ago (Altman and Das, 1965). doi: 10.1101/cshperspect.a021741, Albert, P. R., and Benkelfat, C. (2013).

Mol. [1] CREB is necessary for the late stage of long-term potentiation. Downstream of neuronal activity, the PKA, mitogen-activated protein kinase (RSK [p90 ribosomal protein S6 kinase]/MAPK), and CaMKIV (Ca2+/calmodulin-dependent protein kinase IV) kinase pathways result in CREB phosphorylation at Ser133. Pharmaceuticals (Basel) 3, 839–915.

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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