Perirhinal cortex hyperexcitability in pilocarpine-treated epileptic rats.
The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABA(A) receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyperexcitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy.
Benini
Ruba
R
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Longo
Daniela
D
Biagini
Giuseppe
G
Avoli
Massimo
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D020534:Parahippocampal Gyrus / Q000187:drug effects / Q000503:physiopathology*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010862:Pilocarpine