title: Interneurons spark seizure-like activity in the entorhinal cortex.
abstract: Excessive neuronal synchronization is presumably involved in epileptiform synchronization. However, the respective roles played by interneurons (GABAergic) and principal (glutamatergic) cells during interictal and ictal discharges remain unclear. Here, we employed tetrode wire recordings to establish the involvement of these two cell types in 4-aminopyridine-induced interictal- and low-voltage fast (LVF) onset ictal-like discharges in the rat entorhinal cortex in an in vitro slice preparation. We recorded a total of 90 single units (69 putative interneurons, 17 putative principal and 4 unclassified cells) from 36 slices, and found that: (i) interneurons (66.7%) were more likely to fire during interictal discharges than principal cells (35.3%); (ii) interneuron activity increased shortly before LVF ictal onset, whereas principal cell activity did not change; (iii) interneurons and principal cells fired at high rates throughout the tonic phase of the ictal discharge; however, (iv) only interneurons showed phase-locked relationship with LVF activity at 5-15Hz during the tonic phase. Finally, the association of interneuron firing with interictal discharges was maintained during blockade of ionotropic glutamatergic transmission. Our findings demonstrate the prominent involvement of interneurons in interictal discharge generation and in the transition to LVF ictal activity in this in vitro model of epileptiform synchronization.
authors.affiliation: Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Physiology, McGill University, Montréal, QC H3A 2B4, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lévesque
authors.affiliation: Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Physiology, McGill University, Montréal, QC H3A 2B4, Canada.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Herrington
authors.affiliation: Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Physiology, McGill University, Montréal, QC H3A 2B4, Canada.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Hamidi
authors.affiliation: Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Physiology, McGill University, Montréal, QC H3A 2B4, Canada. Electronic address: massimo.avoli@mcgill.ca.
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D015761:4-Aminopyridine
keywords: 4-Aminopyridine; Interictal discharges; Interneurons; Low-voltage fast onset ictal discharges; Principal cells