The N-Methyl d-Aspartate Glutamate Receptor Antagonist Ketamine Disrupts the Functional State of the Corticothalamic Pathway.
The non-competitive N-methyl d-aspartate glutamate receptor (NMDAR) antagonist ketamine elicits a brain state resembling high-risk states for developing psychosis and early stages of schizophrenia characterized by sensory and cognitive deficits and aberrant ongoing gamma (30-80 Hz) oscillations in cortical and subcortical structures, including the thalamus. The underlying mechanisms are unknown. The goal of the present study was to determine whether a ketamine-induced psychotic-relevant state disturbs the functional state of the corticothalamic (CT) pathway. Multisite field recordings were performed in the somatosensory CT system of the sedated rat. Baseline activity was challenged by activation of vibrissa-related prethalamic inputs. The sensory-evoked thalamic response was characterized by a short-latency (∼4 ms) prethalamic-mediated negative sharp potential and a longer latency (∼10 ms) CT-mediated negative potential. Following a single subcutaneous injection of ketamine (2.5 mg/kg), spontaneously occurring and sensory-evoked thalamic gamma oscillations increased and decreased in power, respectively. The power of the sensory-related gamma oscillations was positively correlated with both the amplitude and the area under the curve of the corresponding CT potential but not with the prethalamic potential. The present results show that the layer VI CT pathway significantly contributes in thalamic gamma oscillations, and they support the hypothesis that reduced NMDAR activation disturbs the functional state of CT and corticocortical networks.
Neuropsychologie cognitive et physiopathologie de la schizophrénie, INSERM U1114, Strasbourg, France.|FMTS, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.|Current address: Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.
Paul M
PM
Anderson
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
Nigel C
NC
Jones
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
Terence J
TJ
O'Brien
Neuropsychologie cognitive et physiopathologie de la schizophrénie, INSERM U1114, Strasbourg, France.|FMTS, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
Didier
D
Pinault
D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects*; D014738:Vibrissae / Q000294:innervation
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D013779:Tetrodotoxin; D007649:Ketamine
electrophysiology; gamma oscillations; network noise; schizophrenia; sensory-evoked potential