GABAergic Function as a Limiting Factor for Prefrontal Maturation during Adolescence

Abstract

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 which 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.

BDNF controls cognitive processes related to neuropsychiatric manifestations via autophagic regulation of p62 and GABAA receptor trafficking

“…Besides BDNF, we and others have consistently demonstrated dysfunctions of GABAergic inhibitory neurotransmission in the corticolimbic circuitry of MDD Northoff and Sibille, 2014;Fee et al, 2017), schizophrenia (Caballero and Tseng, 2016;Hoftman et al, 2017), and age-related cognitive decline (Porges et al, 2017), suggesting a critical contribution of this inhibitory pathway to the pathophysiology of mental illnesses.…”

Acute and long-term effects of adolescent methylphenidate on decision-making and dopamine receptor mRNA expression in the orbitofrontal cortex

“…This age also marks a period of extensive development of prefrontal cortex [33], a region of cortex implicated in reward processing and executive control of behavior. To determine how MPH treatment during adolescence affects this type of cognitive function, we examined the effect of MPH on behavioral tasks that rely on prefrontal function [34–37], both during adolescence concurrent with treatment, and in adulthood after treatment was discontinued.…”

Development of transcripts regulating dendritic spines in layer 3 pyramidal cells of the monkey prefrontal cortex: Implications for the pathogenesis of schizophrenia

“…5). Furthermore, developmental changes in cortical GABA system transcripts occur over a protracted period, continuing through adolescence (Caballero and Tseng, 2016; Gonzalez-Burgos et al, 2015). In contrast, most of the pyramidal cell spine-related transcripts examined here stabilized very early in development, as do other markers (Datta et al, 2015b) or measures (Gonzalez-Burgos et al, 2008) of excitatory neurotransmission.…”