Variation in striatal dopamine-related neurophysiology supports age-related modulation of prefrontal GABA/Glutamate balance in human adolescence

COEX 

Changes in neurotransmitter systems, including glutamate, GABA, and dopamine (DA), during adolescence are thought to reflect critical period plasticity mechanisms that support the maturation of prefrontal cortex (PFC) – dependent cognition. Adolescent increases in DA may be a trigger for critical period plasticity, and animal models implicate DA in regulating developmental changes in PFC excitatory (glutamatergic) and inhibitory (GABAergic) balance, however this has not been tested in humans. To interrogate the role of DA in driving changes in PFC GABA/Glu balance, our analyses combine longitudinal 7T T2*-based estimates of striatal tissue iron as a metric of striatal DA-related neurophysiology and magnetic resonance spectroscopic imaging (MRSI) indices of prefrontal GABA/Glu in adolescents and young adults (10-32 years old at baseline). We will present novel, in vivo evidence showing that tissue iron, reflecting DA-related neurophysiology, supports developmental trajectories in PFC GABA/Glu balance, providing support for a model whereby developmental increases in DA are involved in fine-tuning GABA/Glu, and thus excitatory/inhibitory balance, across adolescence. Understanding developmental mechanisms underlying regulation of excitatory/inhibitory transmission can inform psychopathologies, i.e., schizophrenia, that emerge during adolescence and involve changes in DA, GABA, and Glu.