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Opposite effects of ketamine and deep brain stimulation on thalamocortical information processing: Thalamic deep brain stimulation

Abstract : Objective: The neurobiology of schizophrenia remains frustratingly poorly understood when it comes to deal with the development of innovative therapies for an increasing number of patients. The glutamate receptor antagonist ketamine is a translational psychotomimetic substance that induces psychotic-like symptoms in both humans and animals and is widely used in schizophrenia research. In the present study we wanted to evaluate the impact of a single subcutaneous low-dose (<5 mg/kg) administration of ketamine on the state and function of the rodent thalamocortical system. Methods: Multisite network electrophysiological recordings in the rat somatosensory thalamocortical system, natural stimulation of the vibrissae and high-frequency electrical stimulation of the thalamus were conducted during quiet immobile wakefulness. Results: Ketamine induces a hyperactive behavior, increases the amount of spontaneous brain network gamma (30-80 Hz) oscillations, and impairs the ability of the thalamocortical system to discriminate the signal from spontaneous activities during the processing of sensory information. These abnormalities are accompanied by a transient disruption of the long-term potentiation (LTP) of thalamocortical synapses induced by high-frequency deep brain electrical stimulation (hfDBS). Unexpectedly, in contrast to the ketamine action, thalamic stimulation increases the amplitude of the sensory response and decreases the power of ongoing gamma oscillations. The present data support the hypothesis that NMDAr hypofunction is, likely at least through impairment of synaptic plasticity, involved in sensory integration dysfunction, a core feature in schizophrenia. Investigating the link between the state and function of the thalamocortical system may be a key strategy to discover and design innovative therapies against neuropsychiatric disorders.
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Contributor : Didier Pinault Connect in order to contact the contributor
Submitted on : Monday, December 5, 2011 - 7:32:35 PM
Last modification on : Thursday, April 23, 2020 - 2:26:29 PM


  • HAL Id : inserm-00648493, version 1



Didier Pinault, Sofya Kulikova, Elena A. Tolmacheva, Julien Gaudias, Brendan E. Adams, et al.. Opposite effects of ketamine and deep brain stimulation on thalamocortical information processing: Thalamic deep brain stimulation. Conference 2011 of The German Society for Psychiatry, Psychotherapy and Neurology (DGPPN) Symposium: Neural synchrony in schizophrenia and normal brain functioning Chairman: Peter Uhlhaas, Frankfurt; Co-Chair: Christoph Mulert, Hamburg, Nov 2011, Berlin, Germany. ⟨inserm-00648493⟩



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