Sleep-related thalamocortical spindles and delta oscillations are reduced during a ketamine-induced psychosis-relevant transition state

2019.

Mahdavi A., Qin Y., Aubry A. -., Cornec D., Kulikova S., Pinault D.

Schizophrenia is a chronic debilitating disease. Sleep disturbances associated with a reduction in spindles are observed as warning signs prior to the first psychotic episode. Every spindle is a short-lasting (~0.5 s) set of bioelectric sinusoidal waves at the frequency of 10-16 Hz generated within the thalamus. Sleep spindles, easily identifiable in a scalp electroencephalogram, occur hundreds of times during sleep and are implicated in cognition like memory processes. For this reason, spindles are seen as an electrobiomarker of the quality of sleep and cognitive performance. In patients at high risk of psychotic transition, the density (number/time unit) of spindles is reduced. The underlying mechanisms of this change are unknown. Glutamate-mediated neurotransmission in the thalamus plays a key role in the generation of spindles and the etiology of schizophrenia. Therefore, we tested the hypothesis that a reduced function of glutamate receptors at the thalamic level is involved in the psychosis-related reduction in spindles. Using cell-to-network neurophysiological methods in sleeping rats, we demonstrate that systemic administration of the NMDA glutamate receptor antagonist, ketamine, significantly decreases spindle density. This effect is consistently prevented by the widely used antipsychotic drug, clozapine. These original findings support the hypothesis of the involvement of a reduced function of NMDA glutamate receptors in the sleep spindle deficit observed in psychosis-related disorders. The present findings lay the foundation for the development of innovative therapies aimed at preventing psychotic, bipolar, and depressive disorders.

Keywords: EEG, ЭЭГ, NMDA receptors, non-REM sleep, clozapine, pentobarbital, thalamic reticular nucleus, клозапин, пентобарбитал