Figure 1.

Critical Period for experience-dependent plasticity in visual and fear system. (A) Critical period of visual cortex plasticity: visual cortex development is the preeminent model for the study of critical period plasticity and its regulators. Visually depriving one eye by obstructing it early in life yields a life-long loss of visual acuity (amblyopia). Studies of mouse visual cortex development, which has a well-defined 2 weeks critical period that peaks at 1 month after birth, have identified several endogenous “molecular brakes” (colored in red) that close the critical period. These include perineuronal nets (PNNs), myelin-related Nogo receptor (NgR) and PirB, and a nicotinic brake Lynx1. (B) Critical period of fear erasure: a critical period for the fear system near adolescence is emerging through current research. In rodents, extinction can permanently erase fear memory during a preadolescent critical period around 17 days after birth, however, extinction at 24 days or later fails to bar fear memories from re-emerging. Increased PNNs in the amygdala and maturation of input from medial prefrontal cortex (mPFC) to amygdala contribute to the closure of this critical period. Nogo receptor (NgR: colored in light red) also limits fear extinction, but its contribution on fear erasure is not tested. (C) Interventions for enhancing visual cortex plasticity in the adult: counteracting molecular brakes through pharmacological (ChABC, SSRI, HDACI, AChEI: colored in green) and behavioral (environmental enrichment, dark exposure) approaches is a promising therapeutic strategic for recovery from amblyopia. (D) Interventions for fear erasure in the adult: juvenile-like plasticity can be reintroduced in adulthood through pharmacological treatment (ChABC, SSRI treatment) or reconsolidation update. HDACI administration (colored in light green) enhances extinction, but its effect on fear erasure has not been examined yet.