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Edward N. Wilson, Ryan T. Guglietta, Jasmin Lalonde, Avi Chaudhuri; Parallel Regulation of CREB and TORC1 in Response to Monocular Enucleation in Primary Visual Cortex. Invest. Ophthalmol. Vis. Sci. 2011;52(14):81.
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Removal of the "fixing" eye in non-human primates yields significant improvement in visual function of the previously amblyopic eye. The molecular underpinnings that govern this functional recovery remain elusive. One approach to better understand the activity-dependent neuroplasticity that can occur in the visual cortex is to characterize the molecular events that follow monocular enucleation (ME) in animals with normal binocular vision.
We performed ME in infant and adult vervet monkeys (Cercopithecus aethiops) and characterized protein levels in tissue extracted from fresh-frozen primary visual cortex. In particular, we investigated the posttranslational modification of the transcription factor cyclic-AMP response element-binding protein (CREB) through phosphorylation. Furthermore, we examined the expression of transducer of regulated CREB 1 (TORC1), a transcriptional co-regulator necessary for transcription of CREB target genes.
We observed an increase in the level of CREB phosphorylated at serine129 in area V1 of infant and adult monkeys after ME. We have previously shown an upregulation of pCREBser133 across deprived and non-deprived ocular dominance columns in the adult animal. The upregulation of CREB phosphorylated at Ser-129, however, was most conspicuous in deprived eye columns. Expression of the critical CREB co-factor TORC1 was also upregulated after ME in the adult, primarily in the active eye column.
Our data suggest that multiple, parallel signaling pathways converge to activate CREB at specific amino acid residues in neural cells of the primary visual cortex after ME. We believe this to be an important response that promotes neuroprotective and neuroplastic differences between ocular dominance columns through the selective transcription of CREB target genes.
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