Development of frontal GABA and glutamate supports excitation/inhibition balance from adolescence into adulthood.

Abstract

Animal and human postmortem studies provide evidence for changes in gamma-aminobutyric acid (GABA) and glutamate in prefrontal cortex (PFC) during adolescence, suggesting shifts in excitation and inhibition balance consistent with critical period plasticity. However, how GABA and glutamate change through adolescence and how the balance of these inhibitory and excitatory neurotransmitters changes is not well understood in vivo in humans. High field (7 Tesla) Magnetic Resonance Spectroscopic Imaging was used to investigate age-related changes in the balance of GABA/creatine (Cr) and glutamate/Cr in multiple developmentally-relevant regions of frontal cortex in 144 10-30-year-olds. Results indicated a homogenous pattern of age-related Glu/Cr decreases across regions, while age-related changes in GABA/Cr were heterogenous, with a mix of stable and decreasing age effects. Importantly, balance between glutamate/Cr and GABA/Cr in areas of frontal cortex increased through adolescence, suggesting the presence of critical period plasticity in frontal cortex at this significant time of development when adult trajectories are established.