title: Impact of ketamine on neuronal network dynamics: translational modeling of schizophrenia-relevant deficits.
abstract: Subanesthetic doses of the psychomimetic, ketamine, have been used for many years to elicit behavioral effects reminiscent of schizophrenia in both healthy humans and in animal models of the disease. More recently, there has been a move toward the use of simple neurophysiological measures (event-related potentials, brain oscillations) to assay the functional integrity of neuronal circuits in schizophrenia as these measures can be assessed in patients, healthy controls, intact animals, and even in brain slices. Furthermore, alterations of these measures are correlated with basic information processing deficits that are now considered central to the disease. Thus, here we review recent studies that determine the effect of ketamine on these measures and discuss to what extent they recapitulate findings in patients with schizophrenia. In particular, we examine methodological differences between human and animal studies and compare in vivo and in vitro effects of ketamine. Ketamine acts on multiple cortical and subcortical sites, as well as on receptors other than the N-methyl-d-aspartate receptor. Acute ketamine models' changes correlated with psychotic states (e.g. increased baseline gamma-band oscillations), whereas chronic ketamine causes cortical circuit changes and neurophysiological deficits (e.g. impaired event-related gamma-band oscillations) correlated with cognitive impairments in schizophrenia.
authors.affiliation: Laboratory of Neurophysiology, Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. bernat_kocsis@hms.harvard.edu
authors.forename: Bernat
authors.initials: B
authors.lastname: Kocsis
authors.forename: Ritchie E
authors.initials: RE
authors.lastname: Brown
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.forename: Mihaly
authors.initials: M
authors.lastname: Hajos
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008959:Models, Neurological; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology; D057170:Translational Research, Biomedical
chemical_list: D000700:Analgesics; D007649:Ketamine