Neural network of structures in which GABAB receptors regulate absence seizures in the lethargic (lh/lh) mouse model.
In previous work we have shown that GABAB receptors are required for expression of absence seizures in the lethargic (lh/lh) mouse model; that lh/lh mice have increased numbers of GABAB binding sites compared to nonepileptic littermates (designated +/+); and that the magnitude of the increased number of GABAB receptors in lh/lh mice correlated positively with the frequency of absence seizures. We performed this study to delineate the neural network in which GABAB receptors regulate absence seizures in lh/lh mice. We designed three successive screens which had to be passed by a candidate neuronal population before it could be considered a member of the neural network in which GABAB receptors regulate absence seizures. First, the neuronal populations in lh/lh mice had to have enriched GABAB binding sites compared to homologous populations in matched nonepileptic controls; baclofen-displaceable 3H-GABA binding was measured in autoradiograms for this screen. Second, the candidate populations had to generate spike-wave discharges (SWDs) during absence seizures in lh/lh mice; bipolar recording electrodes implanted into candidate neuronal structures were used in this screen. Third, the candidate populations had to demonstrate GABAB receptor-mediated regulation of absence seizures in lh/lh mice; microinjections of a GABAB agonist [(-)-baclofen] and antagonist (CGP 35348) were used for this screen. In this study we found that anterior ventral lateral thalamic nucleus (VLa), nucleus reticularis thalami (NRT), nucleus reuniens (RE) passed all three screens, and hence are members of the neural network in which GABAB receptors regulate absence seizures in lh/lh mice.
D000818:Animals; D001345:Autoradiography; D001418:Baclofen / Q000494:pharmacology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D051379:Mice; D008817:Mice, Mutant Strains; D008845:Microinjections; D009415:Nerve Net / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000502:physiology*; D012894:Sleep Stages
D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C066430:CGP 35348; D001418:Baclofen