1. Intracellular and extracellular recordings were carried out in guinea pig neocortical slices to examine the effects of blockade of excitatory amino acid (EAA) synaptic transmission on population discharges elicited by 4-aminopyridine (4-AP; 50-100-mu-M). 2. After the introduction of 4-AP, two distinct types of rhythmic spontaneous field potentials were recorded in neocortical slices. Type I consisted of multiple spike discharges lasting 20-90 s. These events occurred at a frequency of 0.4-0.2/min. Type II were single field potential spikes (3-6 s in duration) occurring at a higher frequency (2-4/min). 3. Blockade of amino acid-mediated excitatory synaptic transmission with D-2-amino-5-phosphonovaleric acid (D-AP5; 10-30-mu-M) or 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP, 10-mu-M) and 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX; 10-mu-M) abolished the first type of 4-AP-induced field potential, whereas type II events persisted. 4. Type II field events, occurring in the presence of EAA blockers, were further characterized by paired recordings. Events recorded along an axis orthogonal to the pia surface occurred simultaneously without measurable delay. Recordings made along a plane parallel to the pia surface showed that type II discharges propagated over distances of greater-than-or-equal-to 3 mm at an estimated velocity of 7.5 mm/s. 5. Intracellular recordings show that during type II field discharges all cells exhibited phasic depolarizations or hyperpolarizations, depending on the resting membrane potential. When resting potentials were more depolarized than -68 mV, events became mostly hyperpolarizing. 6. Bath application of bicuculline or picrotoxin (both at 25-mu-M) blocked type II discharges, suggesting that they were gamma-aminobutyric acid-A (GABA(A)) receptor-mediated events. Intracellular recordings also show the presence of spontaneous synaptic events not associated with type II discharges. These events were 2-3 mV in amplitude, considerably smaller than events recorded during type II discharges (10-20 mV). The small-amplitude events were also blocked by GABAergic blockers. They most likely represent unitary synaptic events because minimal stimulus applied to the gray matter directly elicited threshold events of similar amplitude (2-3 mV). Intracellular events recorded during type II discharges represented synchronized synaptic potentials consisting of multiple unitary events. 7. When the strength of electrical stimulation was increased, directly evoked GABAergic synaptic events gradually increased in amplitude. On sufficient stimulus strength, directly evoked events were followed by the all-or-none occurrence of synchronized synaptic potentials and the associated type II discharge recorded extracellularly. The latency of occurrence of synchronized synaptic events varied considerably at threshold stimulus (by tens of milli-seconds). As the stimulus strength increased, the latency and variability of the synchronized event were reduced until it merged with the directly evoked event. 8. Our results suggest that GABAergic neurons in the neocortex can be recruited to discharge synchronously by a mechanism independent of synaptic transmission mediated by excitatory amino acids. This capacity for synchronization is uncovered by the convulsant compound 4-AP, resulting in the generation of rhythmic GABA-mediated synaptic potentials in neocortical cells.
