title: Aberrant alpha and gamma oscillations ex vivo after single application of the NMDA receptor antagonist MK-801.
abstract: Clinical symptoms of schizophrenia are associated with altered cortical neuronal oscillations in multiple frequency bands such as alpha (7-13Hz) and gamma (30-90Hz) rhythms. NMDA receptor antagonists induce psychotic symptoms in humans and a schizophrenia-like phenotype in animals, suggesting NMDA receptor dysfunction is involved in the generation of many symptoms of the disorder. We investigated the effects of a single intraperitoneal injection of the NMDA receptor antagonist MK-801 in rats, a model of first-episode schizophrenia, on network oscillations recorded ex vivo in the hippocampus and prefrontal cortex. We found that spontaneous gamma oscillations in hippocampal slices of MK-801-treated animals had a higher peak frequency, but that their rate of occurrence, peak power and Q factor (ratio of peak frequency to half bandwidth) were not affected. Hippocampal gamma oscillations induced by application of acetylcholine displayed a higher peak power, a reduced peak frequency and a shortened induction latency, whereas the Q factor did not change. In the prefrontal cortex, co-application of carbachol and kainate induced two types of network activity in sham animals: continuous gamma oscillations and alternating alpha/gamma oscillations. In MK-801-treated animals, the alternating pattern completely disappeared, and only continuous gamma oscillations could be detected, possessing an increased peak power, decreased peak frequency and decreased Q factor. Alpha oscillations recorded in MK-801-treated animals also had a significantly lower Q factor. In conclusion, our data suggest that NMDA receptor antagonists fundamentally alter the power, peak frequency, dynamics and periodicity of neuronal oscillations in the alpha and gamma frequency band.
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Clément E
authors.initials: CE
authors.lastname: Lemercier
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Constance
authors.initials: C
authors.lastname: Holman
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: zoltan.gerevich@charite.de.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Gerevich
mesh_terms: D000513:Alpha Rhythm / Q000187:drug effects*; D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D065818:Gamma Rhythm / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008839:Microelectrodes; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology; D046509:Tissue Culture Techniques
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Acetylcholine; Alpha oscillations; Gamma rhythm; NMDA receptor antagonist; Q factor; Schizophrenia