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Journal of Neuroscience, Vol 12, 104-115, Copyright © 1992 by Society for Neuroscience
4-aminopyridine-induced epileptiform activity and a GABA-mediated long- lasting depolarization in the rat hippocampus
P Perreault and M Avoli
Montreal Neurological Institute, Quebec, Canada.
Two types of spontaneous filed potentials were recorded in rat hippocampal
slices after addition of 4-aminopyridine (4-AP; 50 microM). One consisted
of brief, epileptiform discharges that occurred at 0.6 +/- 0.2 sec-1 in the
CA3 and CA1 areas. The other type occurred less frequently (0.036 +/- 0.013
sec-1) and was recorded in CA1, CA3, and dentate areas. It corresponded in
all regions to an intracellular long- lasting depolarization (LLD;
duration, 300-1200 msec; peak amplitude, 2- 15 mV) that was abolished by
bicuculline methiodide; therefore, it was mediated by GABAA receptors.
Sectioning experiments and the occurrence of propagation failures indicated
that LLDs could be initiated by any area of the slice. Furthermore, the
propagation of LLDs did not follow any consistent or predictable pattern
along known anatomical hippocampal pathways. Finally, neither the
occurrence nor the propagation of LLDs was affected when excitatory
synaptic transmission was blocked by NMDA and non-NMDA receptor
antagonists. In the presence of antagonists of glutamatergic receptors,
LLDs disappeared after the omission of Ca2+ or the addition of Cd2+ to the
perfusing solution, suggesting that synaptic transmission was required for
their generation. These data indicate that 4-AP discloses both interictal
epileptiform discharges and LLDs in the rat hippocampus. The first type of
activity is presumably related to certain properties of CA3 pyramidal
neurons and the neuronal circuit, whereas LLDs originate from the
spontaneous, periodic activity of GABAergic interneurons located in any
area of the hippocampus, and can propagate to the other areas by the use of
nonsynaptic mechanisms. We propose that 4-AP reveals a novel type of
interaction among GABAergic interneurons that is based on the accumulation
and the dispersion of K+.
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