A Selective Interplay Between Aberrant EPSPKA and INaP Reduces Spike Timing Precision in Dentate Granule Cells of Epileptic Rats

Cereb Cortex. 2010 Apr;20(4):898-911. doi: 10.1093/cercor/bhp156. Epub 2009 Aug 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Biophysics
  • Computer Simulation
  • Dentate Gyrus / pathology*
  • Disease Models, Animal
  • Electric Stimulation / methods
  • Epilepsy / chemically induced
  • Epilepsy / pathology*
  • Excitatory Amino Acid Agents / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • In Vitro Techniques
  • Male
  • Models, Neurological
  • Mossy Fibers, Hippocampal / physiopathology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Pilocarpine
  • Rats
  • Rats, Wistar
  • Receptors, Kainic Acid / metabolism*
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Excitatory Amino Acid Agents
  • Receptors, Kainic Acid
  • Sodium Channel Blockers
  • Sodium Channels
  • Pilocarpine
  • Tetrodotoxin