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

Authors

  • Sofya P. Kulikova,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
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    • Present addresses: NEUROSPIN, CEA-Saclay, 91191, Gif sur Yvette, France.

  • Elena A. Tolmacheva,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
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    • Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, 127994, Moscow, Russia.

  • Paul Anderson,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
    3. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia
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  • Julien Gaudias,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
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    • Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

  • Brendan E. Adams,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
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    • School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.

  • Thomas Zheng,

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
    3. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia
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  • Didier Pinault

    1. INSERM U666, Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg Cedex, France
    2. Université de Strasbourg, Faculté de Médecine, Strasbourg Cedex, France
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Didier Pinault, 1INSERM U666, as above.
E-mail: pinault@unistra.fr

Abstract

Sensory and cognitive deficits are common in schizophrenia. They are associated with abnormal brain rhythms, including disturbances in γ frequency (30–80 Hz) oscillations (GFO) in cortex-related networks. However, the underlying anatomofunctional mechanisms remain elusive. Clinical and experimental evidence suggests that these deficits result from a hyporegulation of glutamate N-methyl-D-aspartate receptors. Here we modeled these deficits in rats with ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a translational psychotomimetic substance at subanesthetic doses. We tested the hypothesis that ketamine-induced sensory deficits involve an impairment of the ability of the thalamocortical (TC) system to discriminate the relevant information from the baseline activity. Furthermore, we wanted to assess whether ketamine disrupts synaptic plasticity in TC systems. We conducted multisite network recordings in the rat somatosensory TC system, natural stimulation of the vibrissae and high-frequency electrical stimulation (HFS) of the thalamus. A single systemic injection of ketamine increased the amount of baseline GFO, reduced the amplitude of the sensory-evoked TC response and decreased the power of the sensory-evoked GFO. Furthermore, cortical application of ketamine elicited local and distant increases in baseline GFO. The ketamine effects were transient. Unexpectedly, HFS of the TC pathway had opposite actions. In conclusion, ketamine and thalamic HFS have opposite effects on the ability of the somatosensory TC system to discriminate the sensory-evoked response from the baseline GFO during information processing. Investigating the link between the state and function of the TC system may conceptually be a key strategy to design innovative therapies against neuropsychiatric disorders.

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