Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.
Proceedings of the National Academy of Sciences of the United States of America May 28, 2024 Elie Adam, Marek Kowalski, Oluwaseun Akeju et al. 30 citations
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.