A Selective Interplay between Aberrant EPSPKA and I-NaP Reduces Spike Timing Precision in Dentate Granule Cells of Epileptic Rats

作者：Epsztein Jerome; Sola Elisabetta; Represa Alfonso; Ben Ari Yehezkel; Crepel Valerie^*

来源：Cerebral Cortex, 2010, 20(4): 898-911.

DOI：10.1093/cercor/bhp156

• dentate granule cells
• I-NaP
• kainate receptors
• mossy fiber sprouting
• spike timing
• temporal lobe epilepsy

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 (EPSPKA) not observed in controls. We report that, in contrast to time-locked spikes generated by EPSPAMPA in control DGCs, aberrant EPSPKA are associated with long-lasting plateaus and jittered spikes during single-spike mode firing. This is mediated by a selective voltage-dependent amplification of EPSPKA through persistent sodium current (I-NaP) activation. In control DGCs, a current injection of a waveform mimicking the slow shape of EPSPKA activates I-NaP and generates jittered spikes. Conversely in epileptic rats, blockade of EPSPKA or I-NaP restores the temporal precision of EPSP-spike coupling. Importantly, EPSPKA 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 EPSPKA and I-NaP severely alters the temporal precision of EPSP-spike coupling in DGCs of chronic epileptic rats.

• 出版日期2010-4