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

In early schizophrenia, attention and perception problems are linked to brain structure and chemistry abnormalities, as well as disrupted brain rhythms in corticothalamic networks. The drug ketamine, which blocks NMDA receptors, mimics these symptoms. In lightly anesthetized rats, a single psychotomimetic dose of ketamine (2.5 mg/kg, subcutaneous) transiently increased baseline beta/gamma oscillations but decreased sensory-induced beta/gamma oscillations. It also disrupted information transfer in the somatosensory thalamus and cortex and reduced sensory-induced thalamocortical connectivity in the broadband gamma range. These findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortico-thalamo-cortical system.

Study at a glance

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.