Severity of atypical absence phenotype in GABAB transgenic mice is subunit specific.
Overexpression of GABA(B)R1a receptors in mice (R1a(+)) results in an atypical absence seizure phenotype characterized by 3- to 6-Hz slow spike-and-wave discharges (SSWDs), reduced synaptic plasticity, and cognitive impairment. Here we tested the hypothesis that increased R1 expression causes atypical absence epilepsy and is not subunit specific. GABA(B)R1b receptors were overexpressed in mouse forebrain (R1b(+)) and confirmed by immunoblot and (3)H-CGP54626A autoradiography. The R1b(+) mice showed a reduction in hippocampal long-term potentiation and GABA(A) receptor-mediated inhibitory postsynaptic currents. R1b(+) mice manifested an electrographic, pharmacological, and behavioral phenotype consistent with atypical absence seizures, though less robust than R1a(+) in terms of SSWD duration and severity of cognitive impairment. These results suggest that abnormal GABA(B)R1b function plays a lesser role in the development of atypical absence epilepsy.
Neurosciences and Mental Health Research Program, The Hospital for Sick Children, Toronto, ON, Canada.
Lee S
LS
Stewart
Ying
Y
Wu
James H
JH
Eubanks
Hua
H
Han
Yevgen
Y
Leschenko
Jose L
JL
Perez Velazquez
Miguel A
MA
Cortez
O Carter
OC
Snead
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004832:Epilepsy, Absence / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D009943:Organophosphorus Compounds / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D018080:Receptors, GABA-B / Q000235:genetics*; D014316:Tritium / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D014316:Tritium; C107353:CGP 54626; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine