Environmental enrichment, BDNF and experience-dependent epigenetic regulation of visual cortex plasticity in juvenile and adult rats

Despite the efforts towards an understanding of the impact of EE on visual functions, several fundamental open questions remain concerning the mechanisms underlying the effects induced by exposure to stimulating environmental conditions on visual system development and plasticity. On the one hand, focusing on visual system development, while it is known that an epigenetic remodelling of chromatin structure controls developmental plasticity in the visual cortex, three main questions have remained open: i) which is the physiological time course of histone modifications? ii) Is it possible, by manipulating the chromatin epigenetic state, to modulate plasticity levels during the CP? iii) How can we regulate histone acetylation in the adult brain in a non-invasive manner? On the other hand, one fundamental aim in EE studies it to find out those molecular factors that are more suitable of being artificially manipulated to mimic or to strengthen the impact of the environment on brain health and plasticity. Among the potential mechanisms underlying the beneficial effects of the most successful treatments proposed so far for enhancing visual cortex plasticity in adult subjects, BDNF emerges as one promising candidate. BDNF has been reported to promote neural plasticity at both the structural and functional level, thus being a very attractive target for the implementation of strategies aimed at drug delivery in amblyopic subjects, with the aim to favour synaptic potentiation and functional recovery of neural connections conveying sensory information from the amblyopic eye to the visual cortex. This promising approach, however, is thwarted by the impossibility for BDNF delivered via peripheral administration to efficiently cross the blood-brain barrier. Focusing on these open issues, the present Thesis is structured in two main parts. In the first part, I investigated the link between histone acetylation and cortical plasticity in the rat visual system, both during the CP and in adult subjects. In the second part, I explored the impact of BDNF intranasal administration as a potentially safe and useful procedure and an effective method to induce visual function recovery in adult amblyopic rats.