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

Field potential and extracellular [K+] ([K+](o)) recordings were made in th e human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 muM) and ionot ropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by r ises in [K+](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontane ously at intervals of 3-27 s. Both field potentials and [K+], elevations we re largest at approximately 1000 mum from the pia. Similar events were indu ced by neocortical electrical stimuli. Application of medium containing low [Ca2+]/high [Mg2+] (n = 3 slices) antagonism of the GABAA receptor (n = 7) or mu -opioid receptor activation (n = 4) abolished these events. Hence, t hey represented network, GABA-mediated potentials mainly reflecting the act ivation of type A receptors following GABA release from interneurons. The G ABAB receptor agonist baclofen (10-100 muM, n = 11) reduced and abolished t he GABA-mediated potentials (ID50 = 18 muM). Baclofen effects were antagoni zed by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n = 6; ID50 = 0 .19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K+](o) rises without mod ifying their rate of occurrence. The GABA-mediated potentials were not infl uenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocy clopentane-trans-1,3-dicarboxylic acid (100 muM, n = 10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-1 00 muM, n = 9). Our data indicate that human neocortical networks challenged with 4-aminopy ridine generate glutamatergic-independent, GABA-mediated potentials that ar e modulated by mu -opioid and GABAB receptors presumably located on interne uron terminals. These events are associated with [K+](o) elevations that ma y contribute to interneuron synchronization in the absence of ionotropic ex citatory synaptic transmission. (C) 2001 IBRO. Published by Elsevier Scienc e Ltd. All rights reserved.