A selective interplay between aberrant EPSPKA and INaP reduces spike timing precision in dentate granule cells of epileptic rats.
Spike timing precision is a fundamental aspect of neuronal information processing in the brain. Here we examined the temporal precision of input-output operation of dentate granule cells (DGCs) in an animal model of temporal lobe epilepsy (TLE). In TLE, mossy fibers sprout and establish recurrent synapses on DGCs that generate aberrant slow kainate receptor-mediated excitatory postsynaptic potentials (EPSP(KA)) not observed in controls. We report that, in contrast to time-locked spikes generated by EPSP(AMPA) in control DGCs, aberrant EPSP(KA) are associated with long-lasting plateaus and jittered spikes during single-spike mode firing. This is mediated by a selective voltage-dependent amplification of EPSP(KA) through persistent sodium current (I(NaP)) activation. In control DGCs, a current injection of a waveform mimicking the slow shape of EPSP(KA) activates I(NaP) and generates jittered spikes. Conversely in epileptic rats, blockade of EPSP(KA) or I(NaP) restores the temporal precision of EPSP-spike coupling. Importantly, EPSP(KA) not only decrease spike timing precision at recurrent mossy fiber synapses but also at perforant path synapses during synaptic integration through I(NaP) activation. We conclude that a selective interplay between aberrant EPSP(KA) and I(NaP) severely alters the temporal precision of EPSP-spike coupling in DGCs of chronic epileptic rats.
Epsztein
Jérôme
J
INMED, INSERM U901, Université de La Méditerranée, Parc scientifique de Luminy, BP 13, 13273, Marseille Cedex 09, France.
Sola
Elisabetta
E
Represa
Alfonso
A
Ben-Ari
Yehezkel
Y
Crépel
Valérie
V
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001703:Biophysics; D003198:Computer Simulation; D018891:Dentate Gyrus / Q000473:pathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018683:Excitatory Amino Acid Agents; D010862:Pilocarpine; D018092:Kainic Acid Receptors; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin
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