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Keywords:

  • human intrinsic bursting;
  • human neocortex;
  • neocortical epilepsy;
  • pediatric epilepsy;
  • persistent sodium current

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.