The ability to increase extracellular GABA predicts frontal cortical gamma synchrony

Abstract

Introduction: Accumulating evidence indicates that synchronization of cortical neuronal activity at gamma-band frequencies is important for various types of perceptual and cognitive processes. Experimental models as well as preclinical studies suggest that GABAA receptor-mediated transmission is required for the induction of network oscillations. However, to date, there is no evidence linking GABA transmission with gamma-band oscillations in humans. Here we show that the ability to increase extracellular GABA levels predicts frontal cortical gamma synchrony in healthy controls. Preclinical and prior imaging work suggests that increased GABA levels enhance the affinity of GABAA receptors for benzodiazepine (BDZ) ligands via a conformational change (termed the ‘GABA-shift’). Theoretically, such an increase in affinity of GABAA receptors should be detected as an increase in the binding of a GABAA BDZ-receptor site-specific PET radioligand.