title: The circuitry of atypical absence seizures in GABA(B)R1a transgenic mice.
abstract: The objective of the current study was to determine the origin of the slow spike and wave discharges (SSWD) in the transgenic mouse with postnatal over-expression of the GABA(B) receptor subunit R1a (GABA(B)R1a(tg)), a mutant animal with a characteristic phenotype consisting of atypical absence seizures and cognitive dysfunction. Using simultaneous electrocorticographic (ECoG) recordings from cortical and depth electrodes in freely moving GABA(B)R1a(tg) mice, we showed that the SSWD in this model of atypical absence seizures arise exclusively from midline thalamus (MT), reticular nucleus of the thalamus (nRT), and the CA1 region of the hippocampus. Lesioning of the MT and nRT with ibotenic acid abolished SSWD. Microinjection of the GABA(B) receptor agonist, (-) baclofen, into MT and nRT exacerbated, and the GABA(B)R antagonist, CGP 35348 abolished, SSWD in the GABA(B)R1a(tg) mice. These data suggest that the nRT and MT are necessary for the generation of SSWD in the GABA(B)R1a(tg) model of atypical absence seizures, and indicate that GABA(B)R-mediated mechanisms within thalamus are necessary for the genesis of SSWD in atypical absence seizures. A putative cortico-thalamo-hippocampal circuit is proposed to explain the unique electrographic findings, ictal behavior, pharmacology, and impairment of cognition that characterize atypical absence seizures.
authors: Neuroscience and Mental Health Program, Faculty of Medicine, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada. xiaomei.wang@utoronto.ca
authors: Xiaomei
authors: X
authors: Wang
authors: Lee
authors: L
authors: Stewart
authors: Miguel A
authors: MA
authors: Cortez
authors: Ying
authors: Y
authors: Wu
authors: Jose Luis Perez
authors: JL
authors: Velazquez
authors: Chun Che
authors: CC
authors: Liu
authors: Liqing
authors: L
authors: Shen
authors: O Carter
authors: OC
authors: Snead
mesh_terms: D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000633:toxicity; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D009474:Neurons / Q000502:physiology*; D020033:Protein Isoforms; D018080:Receptors, GABA-B / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000503:physiopathology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D020033:Protein Isoforms; D018080:Receptors, GABA-B; D007051:Ibotenic Acid