Pharmacology and electrophysiology of a synchronous gaba-mediated potential in the human neocortex

Abstract

Spontaneous synchronous field potentials of negative polarity (duration = 200–700 ms,interevent interval= 9.1 ± 2.9 s; n = 27slices) were recorded, during application of 4-aminopyridine (50 μM), from the superficial/middle layers of slices of human neocortex obtained in the course of neurosurgery for the relief of intractable seizures. The negative-going field potential corresponded to an intracellular long-lasting (duration = 200–1600 ms) depolarization that could be preceded by an excitatory postsynaptic potential-hyperpolarizing inhibitory postsynaptic potential sequence and followed by a long-lasting hyperpolarization. This synchronous activity continued to occur following blockade of excitatory synaptic transmission by excitatory amino acid receptor antagonists, but was greatly reduced and eventually disappeared during application of the GABA_A receptor antagonist bicuculline methiodide. Simultaneous extracellular recordings from three sites in the slice located along an axis parallel to the pia showed that successive synchronous field potentials could originate from any of the three areas. They invaded the other two sites inc. 35.5% of the cases, while propagation to another site only or no propagation at all was observed, respectively, in 44.4% and 20% of instances. The velocity of lateral propagation of the synchronous field potential was7.9 ± 2.5mm/s(range= 4.5−11.8mm/s, n = 6). The modalities of origin and propagation remained the same after blockade of excitatory amino acid receptors. Under these conditions, however, there was a higher incidence of non-propagation and the velocity was significantly lower than in control (5.6 ± 1.9mm/s;range= 2.8–7.7mm/s, n = 6). These data indicate that, in the human neocortex, 4-aminopyridine can reveal a synchronous field potential that correlates with an intracellular long-lasting depolarization and is mainly due to the activation of postsynaptic GABA_A receptors. The action of excitatory amino acid receptors is not necessary for the generation and propagation of these GABA-mediated potentials. We propose that this potential represents a novel mechanism for synchronization and spread of neuronal activity, including seizure-like discharges in the human neocortex.