Seizure-like events in disinhibited ventral slices of adult rat hippocampus.
Epileptic discharges lasting 2-90 s, were studied in vitro in slices from the ventral hippocampus of adult rats, in which inhibition was blocked acutely with bicuculline methiodide (BMI, 5-30 microM) and potassium ([K(+)](o)) raised to 5 mM. These seizure-like events (SLEs) comprised three distinct phases, called here primary, secondary, and tertiary bursts. Primary bursts lasted 90-150 ms. Secondary bursts lasted a further 70-250 ms, comprising a short series of afterdischarges riding on the same depolarization as the primary burst. Finally a train of tertiary bursts started with a peak frequency of 5-10 Hz and could last >1 min. Slices from the ventral hippocampus showed significantly higher susceptibility to SLEs than did dorsal slices. SLEs proved sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. They were insensitive to N-methyl-D-aspartate (NMDA) receptor antagonists; 50 microl D-2-amino-5-phosphonopentanoic acid (D-AP5) did block the transient secondary bursts selectively. SLEs were restricted to the hippocampus proper even if the entorhinal cortex was present. Entorhinal bursts could last <2 s and were only coupled with hippocampal bursts in a minority of slices. Reentry of epileptic bursts occasionally occurred during interictal discharges, but not during the later stages of SLEs. Full-length SLEs always started in CA3 region and could be recorded in minislices containing CA3 plus dentate hilus. Ion-sensitive microelectrodes revealed that interictal discharges were followed by short (2-3 s) [K(+)](o) waves, peaking at approximately 7.5 mM. SLEs were always accompanied by increases in [K(+)](o) reaching approximately 8.5 mM at the start of tertiary bursts; [K(+)](o) then increased more slowly to a ceiling of 11-12 mM. After the end of each SLE, [K(+)](o) fell back to baseline within 10-15 s. SLEs were accompanied by significant increase in synaptic activity, compared with baseline and/or interictal activity, estimated by the variance of the intracellular signal in the absence of epileptic bursts and action potentials (0. 38 mV(2), compared with 0.13 mV(2), and 0.1 mV(2), respectively). No significant increases were observed in the interval preceding spontaneous interictal activity. These studies show that focal assemblies of hippocampal neurons, without long reentrant loops, are sufficient for the generation of SLEs. We propose that a key factor in the transition from interictal activity to SLEs is an increase in axonal and terminal excitability, resulting, at least in part, from elevations in [K(+)](o).
Borck
C
C
Department of Physiology and Biophysics, St. Mary's Hospital Medical School, Imperial College, London W2 1PG.
Jefferys
J G
JG
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C017069:bicuculline methiodide; D011189:Potassium Chloride; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline