Abstract
Electrophysiological recordings during ketamine anesthesia have revealed a slow alternating pattern of high- and low- frequency activity (a "gamma-burst" pattern) that develops with the onset of general anesthesia. We examine the role of NMDA receptor antagonism in generating the gamma-burst pattern and the link between gamma-bursts and dissociative anesthesia. We compare the effects of ketamine with those of the highly selective NMDA receptor antagonist CGS 19755 on multi-site intracranial electrophysiology and behavior in rhesus macaques. Remarkably, we find that animals given a moderate dose of CGS 19755 are able to perform a difficult memory task, while at the same time showing electrophysiological activity similar to ketamine anesthesia, with one key difference: a lack of delta-band LFP modulation. This difference demonstrates that ketamine's ability to drive strong delta-band oscillations relies on additional mechanisms beyond NMDA receptor antagonism alone, and points to a key role for the activity underlying delta-band oscillations in causing anesthesia.