Abstracts

In hippocampal slices, acute ionic or pharmacological manipulations produce spontaneous rhythmic burst discharges. We asked whether such discharges would occur spontaneously in slices made during the weeks after pilocarpine-induced status epilepticus, when animals often exhibit spontaneous seizures. Eighteeen male Sprague Dawley rats (150-250g) were treated with atropine methylbromide (1 mg/kg ) followed after 30 minutes by pilocarpine hydrochloride (380 mg/kg). One hour after the onset of status epilepticus, animals received an injection of diazepam (5 mg) to truncate status.
At time points ranging from 2-18 weeks following status epilepticus, 400 [mu]m thick horizontal hippocampal-entorhinal slices were made using a Vibroslice, placed in an interface recording chamber, maintained at 31.5[deg]C, superfused with 95% O[sub]2[/sub]/5% CO[sub]2[/sub] and bathed in a solution containing (in mM) 126.0 NaCl, 5.0 KCl, 2.0 CaCl, 2.0 MgSO[sub]4[/sub], 26.0 NaHCO[sub]3[/sub], 1.25 NaH[sub]2[/sub]PO[sub]4[/sub], and 10 D-glucose (pH 7.4). Extracellular potassium concentration [K⁺][sub]o[/sub] was altered in some slices by altering the KCl concentration in the bathing medium.
All areas were recorded for a minimum of 5 minutes, prior to adding the stimulating electrode to the slice, to determine the presence of spontaneous bursts. In some slices, simultaneous recordings were made in the pyramidal cell layer of area CA3 and area CA1 or the subiculum. Only slices that were determined to have an adequate response to stimulation of the hilus, Schaffer collateral pathway, or fimbria, were used in the analysis. Animals that exhibited spontaneous seizures had at least one slice that produced spontaneous CA3 bursts. During the first month after status, bursts occurred in only 4% of slices (1/23 slices, n=4 rats), however this number increased to 45% in the second month (9/23, n=4), and 100% in the third and fourth months (23/23, n=4; 31/31, n=6 respectively).
When area CA1 or the subiculum were simultaneously recorded, bursts were smaller in amplitude and followed CA3 bursts, suggesting CA3 was a burst generator. However, the subiculum exhibited secondary bursts that were not recorded in CA3, suggesting the existence of a second burst generator
In bursting slices (6/6), reducing [K⁺][sub]o[/sub] to 3.5 mM decreased the amplitude and frequency of bursts, but did not block them. Conversely, raising [K⁺][sub]o[/sub] to 7.0 mM increased burst amplitude and frequency. In non-bursting slices (7/7[italic]),[/italic] raising [K⁺][sub]o[/sub] to 7.0 mM could induce bursts. Area CA3 develops spontaneous rhythmic burst discharges during the weeks after pilocarpine-induced status. The onset of these events appears to coincide with the onset of spontaneous seizures in the intact animal. These bursts appear to progress from only a small section of CA3 initially to all dorso-ventral levels tested later on. The fact that these bursts invade areas such as the subiculum suggests that they could leave the hippocampus and influence the rest of the brain. (Supported by NS 41490.)