Paired pulse facilitation is turned into paired pulse depression in hippocampal slices after epilepsy induced by 4-aminopyridine in vivo.
Modifications in synaptic plasticity seem to play a key role in the origin and persistence of epilepsy. 4-Aminopyridine (4-AP) induces intense and long lasting epileptic seizures and neurodegeneration when applied into the hippocampus in vivo, effects that seem to be mediated by overactivation of glutamate receptors due to the enhancement of glutamate release from nerve endings. We have studied presynaptic modifications of CA1 responses, using the paired pulse paradigm, in hippocampal slices obtained from 4-AP-treated rats killed during epileptic activity (ex vivo). The paired pulse facilitation (PPF) observed in control slices with interstimulus intervals of 10-30 ms was changed into paired pulse depression (PPD) after 100 microM 4-AP added in vitro. A strikingly similar change was observed in the ex vivo slices even though 4-AP was no longer present in the tissue. We conclude that the facilitation of glutamate release induced by 4-AP becomes chronic after a transient exposure to the drug. This suggests that the facilitated neurotransmitter release induced by 4-AP triggers a more permanent plastic change that may be responsible for the persistence of epilepsy.
Peña
F
F
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, AP 70-253, 04510 Mexico, DF, Mexico.
Bargas
J
J
Tapia
R
R
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine