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bioRxiv · 10.1101/2022.02.21.476564

The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network

Qin, Y.·Mahdavi, A.·Bertschy, M.·Anderson, P. M.·Kulikova, S.·Pinault, D.
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Abstract

In prodromal and early schizophrenia, disorders of attention and perception are associated with structural and chemical brain abnormalities, and with dysfunctional corticothalamic networks exhibiting disturbed brain rhythms. The underlying mechanisms are elusive. The non-competitive NMDA receptor antagonist ketamine simulates the symptoms of prodromal and early schizophrenia, including disturbances in ongoing and task & sensory-related broadband beta-/gamma-frequency (17-29 Hz/30-80 Hz) oscillations in corticothalamic networks. In normal healthy subjects and rodents, complex integration processes, like sensory perception, induce transient, large-scale synchronized beta/gamma oscillations in a time window of a few hundreds of ms (200-700 ms) after the presentation of the object of attention (e.g., sensory stimulation). Our goal was to use an electrophysiological multisite network approach to investigate, in lightly anesthetized rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneous) of ketamine on sensory stimulus-induced oscillations. Ketamine transiently increased the power of baseline beta/gamma oscillations and decreased sensory-induced beta/gamma oscillations. In addition, it disrupted information transferability in both the somatosensory thalamus and the related cortex and decreased the sensory-induced thalamocortical connectivity in the broadband gamma range. In conclusion, the present findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortico-thalamo-cortical system. LAY ABSTRACTCognitive deficit is usual in schizophrenia. Perception- or task-related beta/gamma-frequency oscillations are decreased. In healthy humans and rodents, ketamine-induced NMDA receptor antagonism simulates the symptoms of early schizophrenia and excessively amplifies baseline beta/gamma oscillations. In the present study, using an electrophysiological multisite network approach in a rodent model, it is demonstrated that ketamine, systemically administered at a single psychotomimetic dose, increases baseline beta/gamma oscillations, decreases beta/gamma responses induced by sensory stimulation in a short time window (200-700 ms), and disrupts information transfer in the cortico-thalamo-cortical network. The present findings have mechanistic relevance for cognitive deficits in schizophrenia.

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Qin, Y., Mahdavi, A., Bertschy, M., Anderson, P. M., Kulikova, S., Pinault, D.. 2022-02-22. The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network. https://doi.org/10.1101/2022.02.21.476564

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