Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice

The CA1 region of rat hippocampal slices bathed in 8.5 mM interstitial K+ (K+o) exhibited spontaneous 20- to 90-s electrographic seizures at regular intervals of 1-8 min. In these same slices CA3 neurons generated spontaneous interictal bursts that propagated throughout the pyramidal cell subfields. CA1 electrographic seizures contained components reminiscent of discharges recorded in vivo during tonic-clonic motor seizures. The tonic phase lasted 1-10 s, consisted of a sustained depolarization and firing of CA1 pyramidal cells, and was associated with a negative extracellular potential in the cell layer. The clonic phase lasted tens of seconds and was composed of paroxysmal bursts with afterdischarges in pyramidal cells. 2. Electrographic seizures in CA1 were focal in nature in that they did not invade the CA3 region. Moreover, in approximately 85% of all slices the frequency and amplitude of interictal bursts in CA3 did not change during a CA1 seizure. 3. Both the tonic phase and each clonic discharge of an electrographic seizure were triggered synaptically by a CA3 interictal burst. Microlesions of the Schaffer collateral input abolished CA1 seizures in high K+o, and electrical stimulation of these afferents, in a pattern designed to mimic interictal input, restored seizures. Likewise, similarly patterned electrical stimulation of these fibers in slices bathed in high K+o with the CA3 region removed reliably evoked electrographic seizures with period and duration similar to spontaneous seizures in whole slices. 4. Electrographic seizures but not CA3 interictal bursts could be reversibly abolished by lowering the temperature from 35-37 to 28-30 degrees C or by the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (5-10 microM). The inactive isomer, L-2-amino-5-phosphonovaleric acid (25 microM) did not eliminate seizures. 5. Neither the frequency nor intensity of interictal bursts recorded in the CA3 region changed in the minute preceding seizure initiation. Thus, although the presence of interictal input from the CA3 region is required for CA1 seizure generation, it appears that electrographic seizures do not result from a change in the quality or quantity of interictal input to the CA1 region. 6. During the 30- to 60-s period leading to a seizure the excitability of CA1 pyramidal cells appeared to increase gradually. Over the interseizure interval both CA1 pyramidal cells and glia gradually depolarized, the intensity of interictal bursts recorded in the CA1 region increased, and the extracellular DC potential recorded in the CA1 cell layer drifted negative.(ABSTRACT TRUNCATED AT 400 WORDS)