In mammals the development of the visual system may be altered during a sensitive period by modifying the visual input to one or both eyes. These plastic processes are reduced after the end of the sensitive period. It has been proposed that reduced levels of plasticity are at the basis of the lack of recovery from early visual deprivation observed in adult animals. A developmental downregulation of experience-dependent regulation of histone acetylation has recently been found to be involved in closing the sensitive period. Therefore, we tested whether pharmacological epigenetic treatments increasing histone acetylation could be used to reverse visual acuity deficits induced by long-term monocular deprivation initiated during the sensitive period. We found that chronic intraperitoneal administration of valproic acid or sodium butyrate (two different histone deacetylases inhibitors) to long-term monocularly deprived adult rats coupled with reverse lid-suturing caused a complete recovery of visual acuity, tested electrophysiologically and behaviorally. Thus, manipulations of the epigenetic machinery can be used to promote functional recovery from early alterations of sensory input in the adult cortex.

No abstract

No abstract

During an early phase of enhanced sensitivity called the critical period (CP), monocular deprivation causes a shift in the response of visual cortex binocular neurons in favor of the nondeprived eye, a process named ocular dominance (OD) plasticity. While the time course of the CP for OD plasticity can be modulated by genetic/pharmacological interventions targeting GABAergic inhibition, whether an increased sensory-motor experience can affect this major plastic phenomenon is not known. We report that exposure to environmental enrichment (EE) accelerated the closure of the CP for OD plasticity in the rat visual cortex. Histone H3 acetylation was developmentally regulated in primary visual cortex, with enhanced levels being detectable early in enriched pups, and chromatin immunoprecipitation revealed an increase at the level of the BDNF P3 promoter. Administration of the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to animals reared in a standard cage mimicked the increase in H3 acetylation observed in the visual cortex and resulted in an accelerated decay of OD plasticity. Finally, exposure to EE in adulthood upregulated H3 acetylation and was paralleled by a reopening of the CP. These findings demonstrate a critical involvement of the epigenetic machinery as a mediator of visual cortex developmental plasticity and of the impact of EE on OD plasticity.