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

Abstract

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 μM) 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 μm 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 μ-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 μM, n=11) reduced and abolished the GABA-mediated potentials (ID 50=18 μM). 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 μM, n=10), but decreased in rate with the group I receptor agonist ( S)-3,5-dihydroxyphenylglycine (10–100 μM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by μ-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.