GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms

Neuroscience. 2001;105(4):803-13. doi: 10.1016/s0306-4522(01)00247-0.


Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may contribute to interneuron synchronization in the absence of ionotropic excitatory synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Adult
  • Cortical Synchronization*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Space / metabolism
  • Humans
  • Neocortex / drug effects
  • Neocortex / physiology*
  • Neural Inhibition / physiology
  • Potassium / metabolism
  • Presynaptic Terminals / physiology
  • Receptors, GABA / physiology
  • Receptors, GABA-B / physiology
  • Receptors, Metabotropic Glutamate / physiology
  • gamma-Aminobutyric Acid / physiology*


  • Excitatory Amino Acid Antagonists
  • Receptors, GABA
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • gamma-Aminobutyric Acid
  • 4-Aminopyridine
  • Potassium