Developmental Downregulation of Histone Posttranslational Modifications Regulates Visual Cortical Plasticity

• Published in: Neuron (Cambridge, Mass.) Mass.), 2007-03, Vol.53 (5), p.747-759
• Main Authors: Putignano, Elena, Lonetti, Giuseppina, Cancedda, Laura, Ratto, Gianmichele, Costa, Mario, Maffei, Lamberto, Pizzorusso, Tommaso
• Format: Article
• Language: English
• Subjects: Acetylation - drug effects; Age Factors; Animals; Critical Period (Psychology); Cyclic AMP Response Element-Binding Protein - metabolism; DEVBIO; Dominance, Cerebral - physiology; Down-Regulation - genetics; Epigenesis, Genetic - physiology; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene expression; Gene Expression Regulation - physiology; Histones - genetics; Histones - metabolism; Hydroxamic Acids - pharmacology; Kinases; MAP Kinase Signaling System - physiology; Mice; Mice, Inbred C57BL; MOLNEURO; Neuronal Plasticity - physiology; Neurons; Phosphorylation; Photic Stimulation; Protein Processing, Post-Translational - physiology; Protein Synthesis Inhibitors - pharmacology; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; Rodents; SIGNALING; Visual Cortex - cytology; Visual Cortex - growth & development; Visual Cortex - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.02.007

The action of visual experience on visual cortical circuits is maximal during a critical period of postnatal development. The long-term effects of this experience are likely mediated by signaling cascades regulating experience-dependent gene transcription. Developmental modifications of these pathways could explain the difference in plasticity between the young and adult cortex. We studied the pathways linking experience-dependent activation of ERK to CREB-mediated gene expression in vivo. In juvenile mice, visual stimulation that activates CREB-mediated gene transcription also induced ERK-dependent MSK and histone H3 phosphorylation and H3-H4 acetylation, an epigenetic mechanism of gene transcription activation. In adult animals, ERK and MSK were still inducible; however, visual stimulation induced weak CREB-mediated gene expression and H3-H4 posttranslational modifications. Stimulation of histone acetylation in adult animals by means of trichostatin promoted ocular dominance plasticity. Thus, differing, experience-dependent activations of signaling molecules might be at the basis of the differences in experience-dependent plasticity between juvenile and adult cortex.