Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons

J Neurosci. 2000 Jul 1;20(13):4829-43. doi: 10.1523/JNEUROSCI.20-13-04829.2000.


Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repetitive manner. Intracellular recordings of layer II/III pyramidal neurons were obtained from adult ferret visual cortical slices maintained in vitro to investigate the ionic mechanisms by which a subgroup of these cells generates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a burst was dependent on the critical interplay between the afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs) that followed each action potential. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na(+), but not Ca(2+), currents. Neither blocking of the transmembrane flow of Ca(2+) nor the intracellular chelation of free Ca(2+) with BAPTA inhibited the generation of intrinsic bursts. In contrast, decreasing the extracellular Na(+) concentration or pharmacologically blocking Na(+) currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II/III pyramidal neurons could be induced to switch from repetitive single spiking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K(+) concentrations, or by potentiation of the persistent Na(+) current with the Na(+) channel toxin ATX II. These results indicate that cortical neurons may dynamically regulate their pattern of action potential generation through control of Na(+) and K(+) currents. The generation of high-frequency burst discharges may strongly influence the response of postsynaptic neurons and the operation of local cortical networks.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Aging
  • Animals
  • Calcium / metabolism*
  • Chelating Agents / pharmacology
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Female
  • Ferrets
  • In Vitro Techniques
  • Lidocaine / analogs & derivatives
  • Lidocaine / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Phenytoin / pharmacology
  • Potassium / pharmacology
  • Potassium Channels / physiology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Sodium / metabolism*
  • Sodium Channels / physiology
  • Tetrodotoxin / pharmacology
  • Visual Cortex / physiology*


  • Chelating Agents
  • Potassium Channels
  • Sodium Channels
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • QX-314
  • Tetrodotoxin
  • Egtazic Acid
  • Phenytoin
  • Lidocaine
  • Sodium
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Potassium
  • Calcium