title: NMDA antagonist ketamine reduces task selectivity in macaque dorsolateral prefrontal neurons and impairs performance of randomly interleaved prosaccades and antisaccades.
abstract: Ketamine, an NMDA receptor antagonist, has been shown to induce behavioral abnormalities in humans that mimic the positive, negative, and most importantly cognitive deficits observed in schizophrenia. Similar cognitive deficits have been observed in nonhuman primates after a subanesthetic dose of ketamine, including an impairment in their ability to perform the antisaccade task, which requires the suppression of a prosaccade toward a flashed stimulus and the generation of a saccade in the opposite direction. The neural basis underlying these cognitive impairments remains unknown. Here, we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine during the performance of randomly interleaved prosaccade and antisaccade trials. Ketamine impeded the monkeys' ability to maintain and apply the correct task rule and increased reaction times of prosaccades and antisaccades. These behavioral changes were associated with an overall increase in activity of PFC neurons and a reduction in their task selectivity. Our results suggest that the mechanism underlying ketamine-induced cognitive abnormalities may be the nonspecific increase in PFC activity and the associated reduction of task selectivity.
authors.affiliation: Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 5C1, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Skoblenick
authors.forename: Stefan
authors.initials: S
authors.lastname: Everling
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012438:Saccades / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine