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Background: In patients with psychotic disorders, sleep spindles are reduced,supporting the hypothesis that the thalamus and glutamate receptors play acrucial etio-pathophysiological role, whose underlying mechanisms remainunknown. We hypothesized that a reduced function of NMDA receptors is involvedin the spindle deficit observed in schizophrenia. Methods: Anelectrophysiological multisite cell-to-network exploration was used toinvestigate, in pentobarbital-sedated rats, the effects of a singlepsychotomimetic dose of the NMDA glutamate receptor antagonist ketamine in thesensorimotor and associative/cognitive thalamocortical (TC) systems. Results:Under the control condition, spontaneously-occurring spindles (intra-frequency:10-16 waves/s) and delta-frequency (1-4Hz) oscillations were recorded in thefrontoparietal cortical EEG, in thalamic extracellular recordings, in dualjuxtacellularly recorded GABAergic thalamic reticular nucleus (TRN) andglutamatergic TC neurons, and in intracellularly recorded TC neurons. The TRNcells rhythmically exhibited robust high-frequency bursts of action potentials(7 to 15 APs at 200-700Hz). A single administration of low-dose ketaminefleetingly reduced TC spindles and delta oscillations, amplified ongoinggamma-(30-80Hz) and higher-frequency oscillations, and switched the firingpattern of both TC and TRN neurons from a burst mode to a single AP mode.Furthermore, ketamine strengthened the gamma-frequency band TRN-TCconnectivity. The antipsychotic clozapine consistently prevented the ketamineeffects on spindles, delta- and gamma-/higher-frequency TC oscillations.Conclusion: The present findings support the hypothesis that NMDA receptorhypofunction is involved in the reduction in sleep spindles and deltaoscillations. The ketamine-induced swift conversion of ongoing TC-TRNactivities may have involved at least both the ascending reticular activatingsystem and the corticothalamic pathway.

A single psychotomimetic dose of ketamine decreases thalamocortical spindles and delta oscillations in the sedated rat