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.

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…The organization of perineuronal nets is delayed by dark-rearing, an environmental condition that extends the duration of the critical period, and degradation of PNNs in the adult rodent reinstates critical period plasticity in visual cortex (Pizzorusso et al, 2002). This work suggests that the formation of perineuronal nets is a molecular mechanism that functions as a 'brake' on critical period plasticity (Bavelier et al, 2010).…”

“…Within the visual system, this increase in inhibitory signaling initiates the opening of a critical period for ocular dominance (Bavelier et al, 2010;Hensch, 2004). The balance between excitatory and inhibitory signaling appears to be a primary regulator of the onset of critical period plasticity.…”

“…However, subsequent to the delineation of the molecular mechanisms governing critical period plasticity, continued research has identified a range of manipulations that can reintroduce plasticity in the visual beyond the critical developmental period (Bavelier et al, 2010). In general, these interventions work by removing structural barriers to plasticity, including perineuronal nets and myelin-associated inhibitory proteins or by altering the balance between local excitatory and inhibitory neurotransmission.…”

Achievements and challenges in the biology of environmental effects

“…Neuroplasticity refers to the ability of the brain to be molded by experiences or to remodel itself as a response to injury (23)(24)(25)(26). Initially, this was considered in relation to "sensitive periods" in early life, but it is now clear that the brain is intrinsically plastic right into adult life, although plasticity reduces with increasing age.…”

“…In addition, plasticity can be increased by vigorous extended exercise. It is adaptive for an organism to be able to regulate plasticity through a series of molecular "brakes" and "accelerators" to ensure both adaptability to changing conditions and stable functioning, and there is a need for a greater understanding of the molecular and cellular mechanisms involved (23).…”