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Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric patients with epilepsy

Authors

  • Andrew K. Tryba,

    1. Department of Physiology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
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    • A.K.T. and C.C.K. are co-first authors.

  • Catherine C. Kaczorowski,

    1. Department of Physiology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    2. Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI, USA
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    • A.K.T. and C.C.K. are co-first authors.

  • Faiza Ben-Mabrouk,

    1. Department of Physiology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
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  • Frank P. Elsen,

    1. Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI, USA
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  • Sean M. Lew,

    1. Department of Neurosurgery, The Medical College of Wisconsin, Milwaukee, WI, USA
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  • Charles J. Marcuccilli

    1. Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI, USA
    2. Department of Neurosurgery, The Medical College of Wisconsin, Milwaukee, WI, USA
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Andrew Kieran Tryba, as above.
E-mail: atryba@mcw.edu

Abstract

Neocortical oscillations result from synchronized activity of a synaptically coupled network and can be strongly influenced by the intrinsic firing properties of individual neurons. As such, the intrinsic electroresponsive properties of individual neurons may have important implications for overall network function. Rhythmic intrinsic bursting (rIB) neurons are of particular interest, as they are poised to initiate and/or strongly influence network oscillations. Although neocortical rIB neurons have been recognized in multiple species, the current study is the first to identify and characterize rIB neurons in the human neocortex. Using whole-cell current-clamp recordings, rIB neurons (n = 12) are identified in human neocortical tissue resected from pediatric patients with intractable epilepsy. In contrast to human regular spiking neurons (n = 12), human rIB neurons exhibit rhythmic bursts of action potentials at frequencies of 0.1–4 Hz. These bursts persist after blockade of fast excitatory neurotransmission and voltage-gated calcium channels. However, bursting is eliminated by subsequent application of the persistent sodium current (INaP) blocker, riluzole. In the presence of riluzole (either 10 or 20 μm), human rIB neurons no longer burst, but fire tonically like regular spiking neurons. These data demonstrate that INaP plays a critical role in intrinsic oscillatory activity observed in rIB neurons in the human neocortex. It is hypothesized that aberrant changes in INaP expression and/or function may ultimately contribute to neurological diseases that are linked to abnormal network activity, such as epilepsy.

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