The inhibitory GABAergic system in the prefrontal cortex develops substantially during adolescence, establishing a healthy balance between excitation and inhibition and contributing to the maturation of cognitive and emotional functioning. My research found that when adolescent stress is combined with genetic deficiency of Npas4, an activity-dependent transcription factor important for GABAergic maturation, mice show deficits in prefrontal cortex-dependent cognitive tasks. Anxiety-like behavior also decreases from adolescence to adulthood in healthy wild-type mice, but remains elevated mice exposed to adolescent stress. I also found that chronic adolescent stress disrupts the maturation of specific components of the GABAergic system, including parvalbumin cells and their surrounding perineuronal nets, in a sex- and age-dependent manner. Disrupted GABAergic maturation by adolescent stress may contribute to the pathogenesis of neuropsychiatric disorders like schizophrenia and anxiety, which often emerge during adolescent ages.
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Adolescent stress disrupts the maturation of anxiety-related behaviors and alters the developmental trajectory of the prefrontal cortex in a sex- and age-specific manner. Page CE, Coutellier L. Neuroscience (2018)
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Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic maturation and adult cognitive flexibility. Page CE, Alexander J, Shepard R, Coutellier L. Genes Brain and Behavior (2018)