Critical period regulation across multiple timescales

Abstract

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Here, we consider recent progress in the biological basis of critical periods as a unifying rubric for understanding plasticity across multiple timescales. Notably, the maturation of parvalbumin-positive (PV) inhibitory neurons is pivotal. These fast-spiking cells generate gamma oscillations associated with critical period plasticity, are sensitive to circadian gene manipulation, emerge at different rates across brain regions, acquire perineuronal nets with age, and may be influenced by epigenetic factors over generations. These features provide further novel insight into the impact of early adversity and neurodevelopmental risk factors for mental disorders.

Keywords: circadian clock; critical period; gamma oscillations; parvalbumin.

Fig. 1.

CP regulation across multiple timescales. (A) Schematic representing a CP in early development. The onset of plasticity is controlled by the maturation of inhibitory cells in cortex. (B) The emergent oscillatory expression of circadian genes within PV inhibitory cells contributes to their maturation and the beginning of CP plasticity. (C) Altered experience during CPs induces a transient, rapid rise in gamma oscillatory activity, which is hypothesized to enable circuit plasticity. (D) Dynamic methylation rates (red circles) and chromatin stability across the life span may regulate levels of plasticity during CPs, adulthood, and aging.

Fig. 2.

Sequential CP plasticity is observed in the mouse brain. Time windows for peak plasticity in barrel cortex (173, 174), auditory cortex (1), insular cortex (154), amygdala (175), visual cortex (30, 31, 75), and higher cognitive areas (176, 177) are staggered in register with the respective emergence of PV circuits (178, 179). Similarly, hierarchical development of monkey visual cortical regions is correlated with PV circuit maturation (33).