GABAergic Function as a Limiting Factor for Prefrontal Maturation during Adolescence

Adolescence is a vulnerable period for the onset of mental illnesses including schizophrenia and affective disorders, yet the neurodevelopmental processes underlying this vulnerability remain poorly understood. The prefrontal cortex (PFC) and its local GABAergic system are thought to contribute to the core of cognitive deficits associated with such disorders. However, clinical and preclinical end-point analyses performed in adults are likely to give limited insight into the cellular mechanisms that are altered during adolescence but are only manifested in adulthood. This perspective summarizes work regarding the developmental trajectories of the GABAergic system in the PFC during adolescence to provide an insight into the increased susceptibility to psychiatric disorders during this critical developmental period.

TrendsAdolescence is a transitional developmental period characterized by refinement of executive functions associated with the protracted development of the prefrontal cortex (PFC).Interestingly, adolescence is also a period for the onset of psychiatric disorders of affect and cognition, yet the neurobiological mechanisms underlying this vulnerability remain unclear.Defining the developmental correspondence between humans and rodents is a necessary step to study the neural substrates that confer such developmental vulnerability.The prefrontal GABAergic system of rodents experiences dramatic functional changes during adolescence whose arrest leads to an imbalance of the excitatory–inhibitory transmission and a hypofunctional PFC.The systematic dissection of this model will be valuable for understanding the rules governing normal prefrontal development in humans and ameliorating the burden of developmental disorders.