title: Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia.
abstract: Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cordon
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Nicolás
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Arrieta
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
authors.forename: Eneko
authors.initials: E
authors.lastname: Lopetegui
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: López-Azcárate
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain; Neurophysiology Service, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Alegre
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain; Neurophysiology Service, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain. Electronic address: jartieda@unav.es.
authors.forename: Julio
authors.initials: J
authors.lastname: Artieda
authors.affiliation: Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain. Electronic address: mvustarroz@unav.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Valencia
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D058256:Brain Waves; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004567:Electrodes, Implanted; D007649:Ketamine; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D017208:Rats, Wistar; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D007649:Ketamine
keywords: Animal models; Cortico-basal ganglia network; Cross-frequency coupling; Hyperlocomotion; Ketamine; Schizophrenia