Electrical and chemical long-term depression do not attenuate low-Mg2+-induced epileptiform activity in the entorhinal cortex.
OBJECTIVE
Low-frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long-term depression (LTD) or depotentiation of a seizure-related long-term potentiation has been proposed to be part of the underlying mechanism. With the low-Mg(2+)-model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity.


METHODS
The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low-frequency paired-pulse stimulation (3 x 900 paired pulses at 1 Hz), and by (b) bath-applied N-methyl-D-aspartate (NMDA, 20 microM) changes time-to-onset, duration, and frequency of seizure-like events (SLEs) induced by omitting MgSO(4) from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low-frequency stimulation after onset of low-Mg(2+)-induced epileptiform activity.


RESULTS
LTD, induced either by low-frequency stimulation or by bath-applied NMDA, had no effect on time-to-onset, duration, and frequency of SLEs compared with unconditioned slices. Low-frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K(+) concentration.


CONCLUSIONS
Our study demonstrates that neither conditioning LTD nor brief low-frequency stimulation decreases the susceptibility of the entorhinal cortex to low-Mg(2+)-induced epileptiform activity. The present study does not support the hypothesis that low-frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation.
Solger
Jörg
J
Neuroscience Research Center of the Charité, Humboldt University Berlin, Berlin, Germany.
Heinemann
Uwe
U
Behr
Joachim
J
D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D004827:Epilepsy / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008275:Magnesium Deficiency / Q000150:complications; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate