On the structure of ictal events in vitro.
OBJECTIVE
To analyze the cellular and network mechanisms of sustained seizures, we reviewed the literature and present new data on in vitro epileptiform events. We considered single and recurring synchronized population bursts occurring on a time scale from tens of milliseconds to 1 min.


METHODS
We used intracellular and field potential recordings, together with computer network simulations, derived from three types of experimental epileptogenesis: gamma-aminobutyric-acidA (GABAA) blockade, low extracellular [Mg2+]o, and 4-aminopyridine (4-AP).


RESULTS
In all three models, sustained depolarizing synaptic currents developed, either through N-methyl-D-aspartate (NMDA) receptors, depolarizing GABAA receptors, or both. Ectopic action potentials (APs), probably originating in axonal structures, occurred in 4-AP and (as shown by other researchers) after tetanic stimulation; ectopic APs, occurring at sufficient frequency, should also depolarize dendrites, by synaptic excitation, enough to trigger bursts.


CONCLUSIONS
Ictal-like events appear to arise from two basic mechanisms. The first mechanism consists of sustained dendritic depolarization driving a series of dendritic bursts. The second mechanism consists of an increase in axonal and presynaptic terminal excitability driving a series of bursts analogous to interictal spikes.
Traub
R D
RD
IBM Research Division, T.J. Watson Research Center, Yorktown Heights, New York 10598, USA.
Borck
C
C
Colling
S B
SB
Jefferys
J G
JG
D015761:4-Aminopyridine; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D001640:Bicuculline; D001921:Brain / Q000166:cytology / Q000503:physiopathology*; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D008959:Models, Neurological; D016571:Neural Networks, Computer; D009474:Neurons / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D015761:4-Aminopyridine; D001640:Bicuculline