Synchronization of rat hippocampal neurons in the absence of excitatory amino acid-mediated transmission.

Extracellular and intracellular recordings and measurements of extracellular K+ concentration ([K+]o) were performed in the adult rat hippocampus in an in vitro slice preparation. Excitatory amino acid receptor antagonists, as well as the K(+)-channel blockers 4-aminopyridine (4AP, 50 microM) and/or tetraethylammonium (TEA, 5 mM), were added to the bath. Synchronous, negative-going field potentials were recorded in the CA3 stratum radiatum during application of 4AP and excitatory amino acid receptor antagonists. Each of these events was associated with an intracellular long-lasting depolarization and a concomitant rise in [K+]o that attained peak values of 4.3 +/- 0.1 mM (mean +/- S.E.M., n = 6 slices) and lasted 29 +/- 3 s. These field potentials were still recorded in CA3 stratum radiatum after addition of TEA. Under these conditions, prolonged field potentials (40.2 +/- 4.5 s, n = 18) characterized by a prominent positive component; discharge of population spikes also occurred. [K+]o increases associated with these prolonged field-potential discharges had a considerable variability in magnitude (peak value = 3.8-14.1 mM, 6.1 +/- 0.7 mM, n = 5) and duration (14-210 s; 48 +/- 13 s, n = 5). In 8% of the cases spreading depression-like episodes were observed. [K+]o increases during spreading depression-like episodes attained peak values of 11-27 mM (22.8 +/- 0.2 mM, n = 2) and had a duration of 160-396 s (244 +/- 29 s, n = 2). All types of synchronous activity were abolished by the GABAA-receptor antagonist bicuculline methiodide (10 microM) (n = 11). A similar effect was obtained by applying Ca(2+)-free/high-Mg2+ medium (n = 5). Simultaneous field-potential recordings in CA3, CA1, dentate area and subiculum demonstrated that negative-going potentials and prolonged field-potential discharges occurred in all areas in a synchronous fashion. Spreading depression-like episodes were more frequently recorded in the CA1 than in the CA3 area and were not seen in the subiculum or dentate area. These experiments indicate that a glutamatergic-independent, synchronous GABA-mediated potential which is elicited by 4AP in the adult rat hippocampus continues to occur in the presence of TEA. In addition, concomitant application of these K(+)-channel blockers induces a novel type of prolonged field-potential discharge as well as spreading depression-like episodes. Since all synchronous potentials (including spreading depression-like episodes) were abolished by bicuculline methiodide, we conclude that their occurrence is presumably dependent upon the post-synaptic activation of GABAA receptors located on neuronal and glial elements. As excitatory synaptic transmission was nominally blocked under our experimental conditions, we also propose that rises in [K+]o and consequent redistribution processes are per se sufficient to make all types of synchronous activity propagate.