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dc.contributor.authorPulimood, Nisha S
dc.contributor.authorContreras, Minerva
dc.contributor.authorPruitt, Molly E
dc.contributor.authorTarasiewicz, Agnieszka
dc.contributor.authorMedina, Alexandre E
dc.date.accessioned2021-11-01T19:08:37Z
dc.date.available2021-11-01T19:08:37Z
dc.date.issued2021-10-04
dc.identifier.urihttp://hdl.handle.net/10713/17033
dc.description.abstractThe transcription factor CREB is involved in a myriad of cellular functions in the central nervous system. For instance, the role of CREB via phosphorylation at the amino-acid residue Serine (Ser) 133 in expressing plasticity-related genes and activity-dependent neuronal plasticity processes has been extensively demonstrated. However, much less is known about the role of CREB phosphorylation at Ser 142 and 143. Here, we employed a viral vector containing a dominant negative form of CREB, with serine-to-alanine mutations at residue 142 and 143 to specifically block phosphorylation at both sites. We then transfected this vector into primary neurons in vitro or intra-cortically injected it into mice in vivo, to test if these phosphorylation events were important for activity-dependent plasticity. We demonstrated by immunohistochemistry of cortical neuronal cultures that the expression of Arc, a known plasticity-related gene, requires triple phosphorylation of CREB at Ser 133, 142, and 143. Moreover, we recorded visually-evoked field potentials in awake mice before and after a 7-day period of monocular deprivation to show that, in addition to CREB phosphorylation at Ser 133, ocular dominance plasticity in the visual cortex also requires CREB phosphorylation at Ser 142/143. Our findings suggest that Ser 142/143 phosphorylation is an additional post-translational modification of CREB that triggers the expression of specific target genes and activity-dependent neuronal plasticity processes.SIGNIFICANCE STATEMENTThe transcription factor CREB triggers the expression of numerous different gene clusters in response to different cellular stimuli. Previous studies have shown that CREB can be activated by phosphorylation at several of its serine residues. We discovered that ocular dominance plasticity, a type of activity-dependent plasticity in the visual cortex, requires the phosphorylation of three different serine residues on CREB (Ser133, Ser142, and Ser143). The expression of the critical early gene Arc also requires this triple phosphorylation pattern. Elucidating such phosphorylation patterns of CREB required for activity-dependent gene expression could help us better understand the mechanisms of neuronal plasticity.en_US
dc.description.urihttps://doi.org/10.1523/ENEURO.0217-21.2021en_US
dc.language.isoenen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.ispartofeNeuroen_US
dc.rightsCopyright © 2021 Pulimood et al.en_US
dc.subjectARCen_US
dc.subjectCREBen_US
dc.subjectNeuronal plasticityen_US
dc.subjectOcular dominanceen_US
dc.subjectVEPen_US
dc.subjectgene expressionen_US
dc.titlePhosphorylation of CREB at Serine 142 and 143 is essential for visual cortex plasticityen_US
dc.typeArticleen_US
dc.identifier.doi10.1523/ENEURO.0217-21.2021
dc.identifier.pmid34607805
dc.source.countryUnited States


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