SYNCHRONIZATION OF RAT HIPPOCAMPAL-NEURONS IN THE ABSENCE OF EXCITATORY AMINO ACID-MEDIATED TRANSMISSION

Extracellular and intracellular recordings and measurements of extrace llular K+ concentration ([K+](o)) were performed in the adult rat hipp ocampus in an in vitro slice preparation. Excitatory amino acid recept or antagonists, as well as the K+-channel blockers 4-aminopyridine (4A P, 50 mu M) and/or tetraethylammonium (TEA, 5 mM), were added to the b ath. Synchronous, negative-going field potentials were recorded in the CA3 stratum radiatum during application of 4AP and excitatory amino a cid 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 r ecorded in CA3 stratum radiatum after addition of TEA. Under these con ditions, prolonged field potentials (40.2 +/- 4.5 s, n = 18) character ized by a prominent positive component; discharge of population spikes also occurred. [K+](o) increases associated with these prolonged fiel d-potential discharges had a considerable variability in magnitude (pe ak 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 epi sodes were observed. [K+](o) increases during spreading depression-lik e episodes attained peak values of 11-27 mM (22.8 +/- 0.2 mM, n = 2) a nd had a duration of 160-396 s (244 +/- 29 s, n = 2). All types of syn chronous activity were abolished by the GABA(A)-receptor antagonist bi cuculline methiodide (10 mu M) (n = 11). A similar effect was obtained by applying Ca2+-free/high-Mg2+ medium (n = 5). Simultaneous field-po tential recordings in CA3, CA1, dentate area and subiculum demonstrate d that negative-going potentials and prolonged field-potential dischar ges occurred in all areas in a synchronous fashion. Spreading depressi on-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 exp eriments indicate that a glutamatergic-independent, synchronous GABA-m ediated potential. which is elicited by 4AP in the adult rat hippocamp us continues to occur in the presence of TEA. In addition, concomitant application of these K+-channel blockers induces a novel type of prol onged field-potential discharge as well as spreading depression-like e pisodes. Since all synchronous potentials (including spreading depress ion-like episodes) were abolished by bicuculline methiodide, we conclu de that their occurrence is presumably dependent upon the post-synapti c activation of GABA, 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 con sequent redistribution processes are per se sufficient to make all typ es of synchronous activity propagate.