Figure 3: The process of plasticity reactivation induced by EE is associated with signal transduction pathways that involve the activation of long-distance neuromodulatory systems and IGF-1 signaling. We propose a model in which the interplay between 5-HT and IGF-1 transmission, in parallel or in series, shifts the inhibitory/excitatory balance in favour of excitation thus activating intracellular mechanisms that eventually promote epigenetic modifications of chromatin structure that, in turn, allow for the expression of plasticity genes in adult life. A pharmacological reduction of inhibitory transmission could promote Bdnf expression and activate physiological mechanisms that may drive the degradation of extracellular matrix (ECM) components that are inhibitory for plasticity. 5-HT and IGF-1 signaling, respectively, may also directly activate Bdnf expression or enhance the ECM remodeling. Bdnf-trkB signaling might upregulate additional gene expression patterns associated with functional modifications in the VC. This could also alter the balance of intracortical inhibition and excitation. Degradation of ECM components may modify the inhibition/excitation ratio in the visual system. The interaction between BDNF-trkB signaling and ECM reorganization has yet to be explored. Continuous arrows represent established interactions between molecular and cellular processes mentioned (boxes). Dashed lines represent interactions that remain to be ascertained.