title: Spike-wave discharges in adult Sprague-Dawley rats and their implications for animal models of temporal lobe epilepsy.
abstract: Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. Genetic absence epilepsy rats of Strasbourg (GAERS) and Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence, but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies using the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2- to 3-month-old naive female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest, which continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports (Buzsáki et al., 1990). Housing in atypical lighting during early life appeared to facilitate the incidence of SWDs. Spike-wave discharges were often accompanied by behaviors similar to stage 1-2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to that of hippocampal theta rhythm during exploration for a given animal, typically 7-8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting that neuronal activity in the hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal, and cortical neurons do not prevent SWDs, at least in this animal model. The results suggest that it is possible that SWDs occur in rodent models of TLE and that investigators mistakenly assume that they are stage 1-2 limbic seizures. We discuss the implications of the results and ways to avoid the potential problems associated with SWDs in animal models of TLE.
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; The Sackler Institute of Biomedical Sciences, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Patrice S
authors.initials: PS
authors.lastname: Pearce
authors.affiliation: Department of Neurology, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Friedman
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lafrancois
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
authors.forename: Sloka S
authors.initials: SS
authors.lastname: Iyengar
authors.affiliation: Center for Neural Science, 4 Washington Place, New York University, New York, NY 10003, USA.
authors.forename: André A
authors.initials: AA
authors.lastname: Fenton
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Maclusky
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Child & Adolescent Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; Department of Physiology & Neuroscience, New York University Langone Medical Center, New York, NY 10016, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: hscharfman@nki.rfmh.org.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data*; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010862:Pilocarpine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology
chemical_list: D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: Absence seizures; Female; Limbic seizures; Pilocarpine; Thalamocortical oscillations; Video-EEG