Transgenic mice over-expressing GABA(B)R1a receptors acquire an atypical absence epilepsy-like phenotype.
In this study, we tested whether over-expressing the GABA(B) receptor R1a subtype in transgenic mouse forebrain neurons would be sufficient to induce spontaneous absence seizures. As hypothesized, these transgenic mice develop spontaneous, recurrent, bilaterally synchronous, 3-6 Hz slow spike and wave discharges between 2 and 4 months of age. These discharges are blocked by ethosuximide and exacerbated by baclofen confirming their absence nature. The discharges occur coincident with absence-like behaviors such as staring, facial myoclonus, and whisker twitching. However, in contrast to typical absence epilepsy models, these mice move during the ictal event, display spike and wave discharges in both thalamocortical and limbic circuitry, exhibit impaired hippocampal synaptic plasticity, and display significantly impaired learning ability. Collectively, these features are more characteristic of the less common but more debilitating atypical form of absence epilepsy. Thus, these data support a role for the GABA(B)R1a receptor subtype in the etiology of atypical absence epilepsy.
Wu
Ying
Y
Program in Brain and Behavior, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Chan
Katherine F Y
KF
Eubanks
James H
JH
Guin Ting Wong
C
C
Cortez
Miguel A
MA
Shen
Liqing
L
Che Liu
Chun
C
Perez Velazquez
Jose
J
Tian Wang
Yu
Y
Jia
Zhengping
Z
Carter Snead
O
O
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology*; D001923:Brain Chemistry / Q000235:genetics*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D010641:Phenotype; D018080:Receptors, GABA-B / Q000096:biosynthesis / Q000235:genetics*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid