title: Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex.
abstract: Allotetrahydrodeoxycorticosterone (THDOC) belongs to a class of pregnane neurosteroidal compounds that enhance brain inhibition by interacting directly with GABAA signaling, mainly through an increase in tonic inhibitory current. Here, we addressed the role of THDOC in the modulation of interictal- and ictal-like activity and associated high-frequency oscillations (HFOs, 80-500 Hz; ripples: 80-200 Hz, fast ripples: 250-500 Hz) recorded in vitro in the rat piriform cortex, a highly excitable brain structure that is implicated in seizure generation and maintenance. We found that THDOC: (i) increased the duration of interictal discharges in the anterior piriform cortex while decreasing ictal discharge duration in both anterior and posterior piriform cortices; (ii) reduced the occurrence of HFOs associated to both interictal and ictal discharges; and (iii) prolonged the duration of 4-aminopyridine-induced, glutamatergic independent synchronous field potentials that are known to mainly result from the activation of GABAA receptors. Our results indicate that THDOC can modulate epileptiform synchronization in the piriform cortex presumably by potentiating GABAA receptor-mediated signaling. This evidence supports the view that neurosteroids regulate neuronal excitability and thus control the occurrence of seizures.
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Qc, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Herrington
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Qc, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Lévesque
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Qc, Canada. Electronic address: massimo.avoli@mcgill.ca.
authors.forename: M
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002540:Cerebral Cortex / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D010879:Piperazines; D026902:Potassium Channel Blockers; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D015761:4-Aminopyridine
keywords: 4-aminopyridine; 4AP; ACSF; HFOs; THDOC; allotetrahydrodeoxycorticosterone; artificial cerebrospinal fluid; epileptiform synchronization; high-frequency oscillations; ictogenesis