Ripple activity in the dentate gyrus of dishinibited hippocampus-entorhinal cortex slices

Fast oscillations at similar to 200 Hz, termed ripples, occur in the hippocampus and cortex of several species, including humans, and are thought to play a role in physiological (e.g., sensory information processing or memory consolidation) and pathological (e.g., seizures) processes. Blocking gamma-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition represents one of the most often used models of epileptiform discharge. Here we found that bath application of the GABA(A) receptor antagonist picrotoxin (50 mu M) to mouse hippocampusentorhinal cortex slices induced spontaneous epileptiform activity (duration 536.6 +/- 146.1 msec, mean +/- SD; interval of occurrence 14.8 +/- 3.3 sec, n = 12) with two distinct phases of discharge; the first was characterized, in the dentate gyrus only, by high-frequency, field oscillations (ripples) at 206.3 +/- 23.4 Hz (n = 12), whereas the second component corresponded to afterdischarges in the theta range frequency. Ripples, which were also recorded in minislices only of the dentate gyrus, were unaffected by application of the mu-opioid receptor agonist (D-Ala2-N-Me-Phe,Gly-ol)enkephalin (10 mu M; n = 6) or the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonate (10 mu M; n = 5). In contrast, the non-NMDA glutamatergic receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 mu M; n = 5) completely blocked all picrotoxin-induced activities. In addition, application of the GABA(B) receptor agonist baclofen (0.01-0.5 mu M; n = 6) dose dependently and reversibly abolished all picrotoxin-induced activities. We also found that application of the gap-junction decouplers carbenoxolone (0.2-0.5 mM; n = 6) or octanol (0.2-0.5 mM; n = 3) blocked the second phase while leaving ripples unchanged. These findings demonstrate that the disinhibited dentate gyrus can generate ripple activity at similar to 200 Hz that is contributed by ionotropic glutamatergic mechanisms and is not dependent on either GABAA receptor-mediated or gap-junction mechanisms. (c) 2005 Wiley-Liss, Inc.