Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro

J Neurophysiol. 2006 Nov;96(5):2564-77. doi: 10.1152/jn.00446.2006. Epub 2006 Jul 26.


Most types of electrographic epileptiform activity can be characterized by isolated or repetitive bursts in brain electrical activity. This observation is our motivation to determine mechanisms that underlie bursting behavior of neuronal networks. Here we show that the persistent sodium (Na(P)) current in mouse neocortical slices is associated with cellular bursting and our data suggest that these cells are capable of driving networks into a bursting state. This conclusion is supported by the following observations. 1) Both low concentrations of tetrodotoxin (TTX) and riluzole reduce and eventually stop network bursting while they simultaneously abolish intrinsic bursting properties and sensitivity levels to electrical stimulation in individual intrinsically bursting cells. 2) The sensitivity levels of regular spiking neurons are not significantly affected by riluzole or TTX at the termination of network bursting. 3) Propagation of cellular bursting in a neuronal network depended on excitatory connectivity and disappeared on bath application of CNQX (20 microM) + CPP (10 microM). 4) Voltage-clamp measurements show that riluzole (20 microM) and very low concentrations of TTX (50 nM) attenuate Na(P) currents in the neural membrane within a 1-min interval after bath application of the drug. 5) Recordings of synaptic activity demonstrate that riluzole at this concentration does not affect synaptic properties. 6) Simulations with a neocortical network model including different types of pyramidal cells, inhibitory interneurons, neurons with and without Na(P) currents, and recurrent excitation confirm the essence of our experimental observations that Na(P) conductance can be a critical factor sustaining slow population bursting.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Computer Simulation
  • Data Interpretation, Statistical
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Gap Junctions / physiology
  • Male
  • Mice
  • Models, Neurological
  • Neocortex / cytology
  • Neocortex / physiology*
  • Nerve Net / cytology
  • Nerve Net / physiology*
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Riluzole / pharmacology
  • Sodium Channels / physiology*
  • Synapses / physiology
  • Tetrodotoxin / pharmacology


  • Excitatory Amino Acid Antagonists
  • Sodium Channels
  • Tetrodotoxin
  • Riluzole