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Impaired neuronal operation through aberrant intrinsic plasticity in epilepsy
Author(s) -
Artinian Julien,
Peret Angélique,
Mircheva Yanina,
Marti Geoffrey,
Crépel Valérie
Publication year - 2015
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24348
Subject(s) - dentate gyrus , neuroscience , perforant path , hippocampal formation , entorhinal cortex , granule cell , perforant pathway , kainate receptor , excitatory postsynaptic potential , epilepsy , long term potentiation , temporal lobe , postsynaptic potential , psychology , biology , inhibitory postsynaptic potential , ampa receptor , receptor , glutamate receptor , biochemistry
Objective Patients with temporal lobe epilepsy often display cognitive comorbidity with recurrent seizures. However, the cellular mechanisms underlying the impairment of neuronal information processing remain poorly understood in temporal lobe epilepsy. Within the hippocampal formation neuronal networks undergo major reorganization, including the sprouting of mossy fibers in the dentate gyrus; they establish aberrant recurrent synapses between dentate granule cells and operate via postsynaptic kainate receptors. In this report, we tested the hypothesis that this aberrant local circuit alters information processing of perforant path inputs constituting the major excitatory afferent pathway from entorhinal cortex to dentate granule cells. Methods Experiments were performed in dentate granule cells from control rats and rats with temporal lobe epilepsy induced by pilocarpine hydrochloride treatment. Neurons were recorded in patch clamp in whole cell configuration in hippocampal slices. Results Our present data revealed that an aberrant readout of synaptic inputs by kainate receptors triggered a long‐lasting impairment of the perforant path input–output operation in epileptic dentate granule cells. We demonstrated that this is due to the aberrant activity‐dependent potentiation of the persistent sodium current altering intrinsic firing properties of dentate granule cells. Interpretation We propose that this aberrant activity‐dependent intrinsic plasticity, which lastingly impairs the information processing of cortical inputs in dentate gyrus, may participate in hippocampal‐related cognitive deficits, such as those reported in patients with epilepsy. Ann Neurol 2015;77:592–606