Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity.
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.
Putignano
Elena
E
Scuola Normale Superiore, Neurobiology Laboratory, Area Ricerca CNR, via Moruzzi, 1 Pisa 56125, Italy.
Lonetti
Giuseppina
G
Cancedda
Laura
L
Ratto
Gianmichele
G
Costa
Mario
M
Maffei
Lamberto
L
Pizzorusso
Tommaso
T
D000107:Acetylation / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D003423:Critical Period, Psychological; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004292:Dominance, Cerebral / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D010775:Photic Stimulation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D014793:Visual Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology*
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; C012589:trichostatin A; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases