Rhythmic neuronal activity in S2 somatosensory and insular cortices contribute to the initiation of absence-related spike-and-wave discharges

Authors

  • Thomas W. Zheng,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
    2. INSERM U666, Pathophysiology and Psychopathology of Schizophrenia, Strasbourg, France
    3. University of Strasbourg, Faculty of Medicine, Strasbourg, France
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  • Terence J. O’Brien,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
    2. INSERM U666, Pathophysiology and Psychopathology of Schizophrenia, Strasbourg, France
    3. University of Strasbourg, Faculty of Medicine, Strasbourg, France
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  • Margaret J. Morris,

    1. Department of Pharmacology, University of New South Wales, Kensington, New South Wales, Australia
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  • Christopher A. Reid,

    1. Florey Neuroscience Institutes, Melbourne Brain Centre, Melbourne, Australia
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  • Valentina Jovanovska,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
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  • Patrick O’Brien,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
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  • Leena van Raay,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
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  • Arun K. Gandrathi,

    1. Departments of Medicine, Surgery and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
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  • Didier Pinault

    1. INSERM U666, Pathophysiology and Psychopathology of Schizophrenia, Strasbourg, France
    2. University of Strasbourg, Faculty of Medicine, Strasbourg, France
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Address correspondence to: Terence J. O’Brien, Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville 3050, Vic., Australia. E-mail: obrientj@unimelb.edu.au

Summary

Purpose:  The origin of bilateral synchronous spike-and-wave discharges (SWDs) that underlie absence seizures has been widely debated. Studies in genetic rodent models suggest that SWDs originate from a restricted region in the somatosensory cortex. The properties of this initiation site remain unknown. Our goal was to characterize the interictal, preictal and ictal neuronal activity in the primary and secondary cortical regions (S1, S2) and in the adjacent insular cortex (IC) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

Methods:  We performed electroencephalography (EEG) recordings in combination with multisite local field potential (LFP) and single cell juxtacellular recordings, and cortical electrical stimulations, in freely moving rats and those under neurolept-anesthesia.

Key Findings:  The onset of the SWDs was preceded by 5–9 Hz field potential oscillations, which were detected earlier in S2 and IC than in S1. Sustained SWDs could be triggered by a 2-s train of 7-Hz electrical stimuli at a lower current intensity in S2 than in S1. In S2 and IC, subsets of neurons displayed rhythmic firing (5–9 Hz) in between seizures. S2 and IC layers V and VI neurons fired during the same time window, whereas in S1 layer VI, neurons fired before layer V neurons. Just before the spike component of each SW complex, short-lasting high-frequency oscillations consistently occurred in IC ∼20 msec before S1.

Significance:  Our findings demonstrate that the S2/IC cortical areas are a critical component of the macro-network that is responsible for the generation of absence-related SWDs.

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