title: Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.
abstract: Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model.
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan; Department of Neurology, University of Michigan, Ann Arbor, Michigan;
authors.forename: A L
authors.initials: AL
authors.lastname: Althaus
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan;
authors.forename: O
authors.initials: O
authors.lastname: Sagher
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan; Department of Neurology, University of Michigan, Ann Arbor, Michigan;
authors.forename: J M
authors.initials: JM
authors.lastname: Parent
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; and Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan murphyg@umich.edu.
authors.forename: G G
authors.initials: GG
authors.lastname: Murphy
mesh_terms: D000200:Action Potentials; D000328:Adult; D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: dentate gyrus; ectopic; epileptogenesis; intrinsic excitability; seizure