Altered inhibition in lateral amygdala networks in a rat model of temporal lobe epilepsy.
Clinical and experimental evidence indicates that the amygdala is involved in limbic seizures observed in patients with temporal lobe epilepsy. Here, we used simultaneous field and intracellular recordings from horizontal brain slices obtained from pilocarpine-treated rats and age-matched nonepileptic controls (NECs) to shed light on the electrophysiological changes that occur within the lateral nucleus (LA) of the amygdala. No significant differences in LA neuronal intrinsic properties were observed between pilocarpine-treated and NEC tissue. However, spontaneous field activity could be recorded in the LA of 21% of pilocarpine-treated slices but never from NECs. At the intracellular level, this network activity was characterized by robust neuronal firing and was abolished by glutamatergic antagonists. In addition, we could identify in all pilocarpine-treated LA neurons: 1) large amplitude depolarizing postsynaptic potentials (PSPs) and 2) a lower incidence of spontaneous hyperpolarizing PSPs as compared with NECs. Single-shock stimulation of LA networks in the presence of glutamatergic antagonists revealed a biphasic inhibitory PSP (IPSP) in both NECs and pilocarpine-treated tissue. The reversal potential of the early GABA(A) receptor-mediated component, but not of the late GABA(B) receptor-mediated component, was significantly more depolarized in pilocarpine-treated slices. Furthermore, the peak conductance of both fast and late IPSP components had significantly lower values in pilocarpine-treated LA cells. Finally, paired-pulse stimulation protocols in the presence of glutamatergic antagonists revealed a less pronounced depression of the second IPSP in pilocarpine-treated slices compared with NECs. Altogether, these findings suggest that alterations in both pre- and postsynaptic inhibitory mechanisms contribute to synaptic hyperexcitability of LA networks in epileptic rats.
Benini
Ruba
R
Montreal Neurological Institute and Department of Neurology, McGill University, Montreal, Canada.
Avoli
Massimo
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000502:physiology; D008297:Male; D016555:Matched-Pair Analysis; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020534:Parahippocampal Gyrus / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D010862:Pilocarpine; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid