Effects of NMDA receptor antagonists on working memory and gamma oscillations, and the mediating role of the GluN2D subunit.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 15, 2025 Chitra Vinnakota, Matthew R Hudson, Kazutaka Ikeda et al. 6 citations
Working memory relies on synchronized brain oscillations involving interactions between pyramidal cells and GABAergic interneurons. NMDA receptor antagonists affect both oscillations and memory, but the link was unclear. In mice performing a touchscreen working memory task, phencyclidine (PCP) disrupted accuracy in wildtype but not GluN2D-knockout mice, indicating PCP's action requires the GluN2D subunit. MK-801, (S)-ketamine, and (R)-ketamine impaired accuracy in both genotypes. PCP increased baseline gamma power in the hippocampus only in wildtypes, while all drugs increased prefrontal gamma power. Low gamma activity during the memory maintenance phase rose when mice answered correctly, and this task-related increase was disrupted by all drugs. The GluN2D subunit mediates PCP's effects on hippocampal gamma and working memory.