PHARMACOLOGY AND ELECTROPHYSIOLOGY OF A SYNCHRONOUS GABA-MEDIATED POTENTIAL IN THE HUMAN NEOCORTEX

Spontaneous synchronous field potentials of negative polarity (duratio n = 200-700 ms, inter event interval = 9.1 +/- 2.9 s; n = 27 slices) w ere recorded, during application of 4-aminopyridine (50 mu M), from th e superficial/middle layers of slices of human neocortex obtained in t he course of neurosurgery for the relief of intractable seizures. The negative-going field potential corresponded to an intracellular long-l asting (duration = 200-1600 ms) depolarization that could be preceded by an excitatory postsynaptic potential-hyperpolarizing inhibitory pos tsynaptic potential sequence and followed by a long-lasting hyperpolar ization. This synchronous activity continued to occur following blocka de of excitatory synaptic transmission by excitatory amino acid recept or antagonists, but was greatly reduced and eventually disappeared dur ing application of the GABA(A) receptor antagonist bicuculline methiod ide. Simultaneous extracellular recordings from three sites in the sli ce located along an axis parallel to the pia showed that successive sy nchronous field potentials could originate from any of the three areas . They invaded the other two sites in c. 35.5% of the cases, while pro pagation to another site only or no propagation at all was observed, r espectively, in 44.4% and 20% of instances. The velocity of lateral pr opagation of the synchronous field potential was 7.9 +/- 2.5 mm/s (ran ge = 4.5-11.8 mm/s, n = 6). The modalities of origin and propagation r emained the same after blockade of excitatory amino acid receptors. Un der these conditions, however, there was a higher incidence of non-pro pagation and the velocity was significantly lower than in control (5.6 +/- 1.9 mm/s; range = 2.8-7.7 mm/s, n = 6). These data indicate that, in the human neocortex, 4-aminopyridine can reveal a synchronous fiel d potential that correlates with an intracellular long-lasting depolar ization and is mainly due to the activation of postsynaptic GABA(A) re ceptors. The action of excitatory amino acid receptors is not necessar y for the generation and propagation of these GABA-mediated potentials . We propose that this potential represents a novel mechanism for sync hronization and spread of neuronal activity, including seizure-like di scharges in the human neocortex.