FUNCTIONAL AND PHARMACOLOGICAL PROPERTIES OF GABA-MEDIATED INHIBITIONIN THE HUMAN NEOCORTEX

This paper describes some functional and pharmacological properties of GABA-mcdiated mechanisms in the human neocortex maintained in vitro i n a slice preparation. Neocortical neurons recorded intracellularly un der normal conditions generate stimulus-induced and spontaneous potent ials that are mediated by the activation of postsynaptic GABA(A) and G ABA(B) receptor subtypes. As reported in other species, pharmacologica l blockade of the GABA(A) receptor makes epileptiform bursts appear in response to extracellular focal stimuli, thus indicating that inhibit ion mediated through the activation of the GABA(A) receptor exerts an important role in controlling neuronal excitability in the human neoco rtex. Spontaneous, prolonged epileptiform discharges are recorded when slices are bathed in Mg2+-free medium, Under these experimental condi tions GABA(A) receptor mediated potentials occur between epileptiform events; moreover their rate of occurrence decreases shortly before the onset of each discharge. Blockade of GABA(A) receptor mediated potent ials during application of Mg2+-free medium (i) prolongs the epileptif orm discharges, (ii) increases the amplitude of their field potential DC shifts, and (iii) augments the concomitant decreases in [Ca2+](o) a nd increases in [K+](o). These findings indicate therefore that GABA(A ) receptor mediated inhibitory potentials are operant during Mg2+-free epileptiform activity, and modulate the occurrence of epileptiform di scharges. Moreover, they may also play a role in controlling the chang es in [Ca2+](o) and [K+](o) that accompany each epileptiform event.