Relationship between synaptic activity and prolonged field bursts in the dentate gyrus of the rat hippocampal slice

1. Previous studies in the dentate granule cell layer of the rat hippocampal slice have demonstrated that nonsynaptic, seizurelike prolonged field bursts occur in conditions of low extracellular Ca2+ concentration ([Ca2+]o) and elevated [K+]o. We hypothesize that the extracellular ion concentration changes induced by synaptic activation of dentate granule cells would be sufficient to initiate these nonsynaptic bursts. 2. Using ion-selective electrode recording, we observed large changes in [Ca2+]o (from 1.3 mM baseline to approximately 0.7 mM) and [K+]o (from 3.5 to approximately 12 mM) in the dentate granule cell layer during repetitive electrical stimulation of the perforant path in rat hippocampal slices. Concomitant with these changes, bursts of population spikes similar to those seen during spontaneous prolonged field bursts appeared between the individual stimulus-evoked responses in the dentate gyrus in many of the slices studied (19 of 27). 3. Blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and gamma-aminobutyric acid-A (GABAA)-mediated synaptic transmission during perforant path stimulation resulted in a marked reduction of the ion concentration changes and a loss of both stimulus-evoked and stimulus-independent population spikes in the dentate gyrus. 4. When slices were perfused with solutions containing [Ca2+]o and [K+]o equivalent to those measured during perforant path stimulation (i.e., 0.7 and 12 mM, respectively), spontaneous prolonged field bursts appeared in the dentate gyrus. Addition of NMDA, non-NMDA, and GABAA receptor antagonists did not prevent the occurrence of these spontaneous bursts. 5. We conclude that changes in [Ca2+]o and [K+]o sufficient to produce prolonged field bursts may be created in the dentate granule cell layer by perforant path stimulation. These effects are dependent on synaptic transmission. Once these ionic conditions occur, they are sufficient to trigger prolonged field bursts independent of fast amino-acid-mediated synaptic transmission. A similar mechanism could be important during the interictal-ictal transition in vivo.