Ketamine, an NMDA-receptor antagonist, produces sedation and dissociation at low doses and unconsciousness at high doses, while generating gamma oscillations (>25 Hz) in the EEG that are interrupted by slow-delta oscillations (0.1–4 Hz) at high doses. Using a biophysical model of cortical circuits, the authors show how NMDA-receptor antagonism leads to disinhibition in neuronal circuits, and how disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition produces gamma oscillations at both doses and slow-delta oscillations at high doses. This work reveals general mechanisms for generating oscillatory brain dynamics and provides insights into ketamine's actions as an anesthetic and therapy for treatment-resistant depression.
Ketamine, an NMDA-receptor antagonist, produces sedation, analgesia, and dissociation at low doses and unconsciousness at high doses, generating gamma oscillations (>25 Hz) in the EEG at both doses, with slow-delta oscillations (0.1-4 Hz) interrupting gamma at high doses. Using a biophysical model of cortical circuits, the authors show how NMDA-receptor antagonism by ketamine leads to disinhibition in neuronal circuits, and how the disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition generates gamma oscillations at both doses and slow-delta oscillations at high doses. This work reveals general mechanisms for oscillatory brain dynamics distinct from previous reports and offers insights into ketamine's action as an anesthetic and therapy for treatment-resistant depression.