SO-M is the sole author of this paper and is responsible for its content. The molecules involved in the modulation of CREB phosphorylation include several neurotransmitters [e.g., dopamine, glutamate, serotonin, gamma-aminobutyric acid (GABA)], growth factors (e.g., insulin-like growth factor 1 IGF-1; vascular endothelial growth factor, VEGF), and neurotrophins (brain-derived neurotrophic factor, BDNF; Yamashima, 2012). Chem. These leucine residues tightly bind to leucine residues of another CREB protein forming a dimer.
Neuron 35, 605–623.
(2007). Ther. Proc.
Viral vectors-mediated gene transfer have been widely used to overexpress CREB. It is widely accepted that adult neurogenesis is involved in memory consolidation and pattern separation, and impairment of these processes has been described in various diseases associated with memory loss, including Alzheimer’s disease (AD; Taupin, 2009; Braun and Jessberger, 2014; Fitzsimons et al., 2014; Cameron and Glover, 2015). Semin. Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells. doi: 10.1002/jnr.10591, Zhao, X., Ueba, T., Christie, B. R., Barkho, B., McConnell, M. J., Nakashima, K., et al.
(2014). It is a key molecule involved in LTM in the majority of species (Bourtchuladze et al., 1994; Yin et al., 1994). J. Neurosci. J. Nutr.
Disord. The expression of pCREB subsided with the emergence of mature neuronal markers such as calbindin in mature granule cells (Jagasia et al., 2009) or NeuN in the SVZ/OB neurogenic system, where pCREB presence declines along a rostral-to-caudal gradient (Giachino et al., 2005; Herold et al., 2011). EMBO J. (2013). doi: 10.1016/j.semcdb.2011.07.002, Bilbao, A., Rieker, C., Cannella, N., Parlato, R., Golda, S., Piechota, M., et al. Neurosci. Nature 472, 466–470. Behav. A typical (albeit somewhat simplified) sequence of events is as follows: A signal arrives at the cell surface, activates the corresponding receptor, which leads to the production of a second messenger such as cAMP or Ca2+, which in turn activates a protein kinase. 33, 1078–1086. Res. In one of these studies, the CREBα/Δ mutation did not affect plasticity in cortical layers II/III of the younger adolescent mice (1–2 months) indicating that different plasticity processes occur at this age. However, the majority of these sites remain unbound due to cytosine methylation, which physically obstructs protein binding..
 There are activator and repressor forms of CREB. (2015). Natl. It highlights the role of CREB as a modulator of AHN, which could underlie its function in memory consolidation mechanisms. doi: 10.1038/345718a0, Deng, W., Aimone, J.
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. , 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.  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.
doi: 10.1126/science.1153252. doi: 10.3390/molecules161210146, Zhang, X., Odom, D. T., Koo, S. H., Conkright, M. D., Canettieri, G., Best, J., et al. miRNAs are known to control both precursor cell survival and differentiation in adult neurogenesis. Finally, hippocampal CREB overexpression improves memory formation (Restivo et al., 2009; Sekeres et al., 2010). This review focuses on the most relevant and recent studies on CREB’s role in memory regulation and its participation in neurogenic processes. CBP and p300 are both chromatin remodelers (histone acetyltransferases) involved in unwinding promoter chromatin and providing the RNA polymerase II (Pol II) transcription machinery access to promoter DNA (Chan and La Thangue, 2001). “Quantifying cell kill and cell survival,” in Basic Clinical Radiobiology, 4th Edn. doi: 10.1254/jphs.cpj06007x, Montminy, M. R., and Bilezikjian, L. M. (1987).
doi: 10.1523/jneurosci.3257-10.2011, Takeda, S., Sato, N., and Morishita, R. (2014). Neurol. J. Neurosci.
25, 294–303. 6:171. doi: 10.3389/fnagi.2014.00171, Taupin, P. (2009). Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription. 261, 396–403. 6, 461–470. Cereb. Kida (2012) revealed the crucial role of CREB in the consolidation of contextual fear conditioning using tamoxifen-inducible expression of a dominant-negative CREB repressor (Vogt et al., 2014).
Mol. Are the dorsal and ventral hippocampus functionally distinct structures? Neuroreport 11, 2577–2580. Clipboard, Search History, and several other advanced features are temporarily unavailable.
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.
Neuroreport 15, 231–234. This induction of PER protein can entrain the circadian clock to light/dark cycles inhibits its own transcription via a transcription-translation feedback loop which can advance or delay the circadian clock. doi: 10.1038/nature09271, Gass, P., and Riva, M. A. doi: 10.1016/j.schres.2014.12.002, Cameron, H. A., and Glover, L. R. (2015). Neuronal competition and selection during memory formation. Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. Biophys. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Natl. Lipid Res. Impact Factor 4.057 | CiteScore 5.8More on impact ›, The Transcriptional Regulation of Memory
Injection of the cAMP-responsive element into the nucleus of aplysia sensory neurons blocks long-term facilitation. In vivo, phase shift-inducing light pulses during the subjective night correlated with CREB phosphorylation in the SCN. Neurosci.
2, 266–270. J. Neurosci. CREB signaling is essential for long-lasting changes in synaptic plasticity that mediates the conversion of short-term memory to long-term memory. doi: 10.1126/science.186870, Burton, C. Z., and Twamley, E. W. (2015). Activation of cAMP signaling facilitates the morphological maturation of newborn neurons in adult hippocampus. A year after CREB was defined, Montminy and Bilezikjian (1987) described CREB as a cellular transcription factor that binds CRE and induces transcription of the somatostatin gene. doi: 10.1016/j.ijdevneu.2014.01.003, Sahay, A., Scobie, K. N., Hill, A. S., O’Carroll, C. M., Kheirbek, M. A., Burghardt, N. S., et al.