Removing brakes on adult brain plasticity: from molecular to behavioral interventions

Abstract

Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these "brakes" are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.

Figure 1.

Evolving plastic capacity across the lifespan (blue arrows) (E/I, Excitatory-inhibitory circuit balance) suggests possible mechanisms for enhancing learning and recovery of function in adulthood (red). (1), Removing structural barriers to rewiring by targeting, for example, perineuronal nets, myelin, or epigenetic status. While effective in resetting brain plasticity in animal models (Table 1), their potential utility in humans remains elusive. (2), Resetting local E/I to a juvenile state where excitation dominates can also effectively promote plasticity in adulthood (Table 1). Noninvasive manipulations, such as the immersive and enriched conditions of video game play, may elicit various neuromodulatory responses, perhaps through feedback signals from higher control centers, to engage brain plasticity and learning in adults.