Cortical versus thalamic mechanisms underlying spike and wave discharges in GAERS.
Genetic absence epilepsy rats from Strasbourg (GAERS) have non-convulsive generalized seizures associated with spike-wave (SW) discharges, which are due to a hyperexcitable state of the thalamo-cortico circuits involving the reticular thalamic nucleus (nRt). Investigation of the primary genetically-determined defect responsible for GAERS epilepsy revealed the following abnormalities: (1) increased effectiveness of AMPA receptors dependent glutamate-mediated transmission; (2) impairment of GABA-mediated transmission in the neocortex; (3) increased amplitude of the voltage-dependent low-threshold Ca2(+)-current (I(T)) in the nRt. The maturational profile of these abnormalities supports the conclusion that the abnormality in the I(T) current in the nRt is the primary genetically-determined defect, which may secondarily induce the other changes found in the neocortex and thalamus of GAERS.
Avanzini
G
G
Department of Neurophysiology, Instituto Nazionale Neurologico C. Besta, Milan, Italy.
de Curtis
M
M
Franceschetti
S
S
Sancini
G
G
Spreafico
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013787:Thalamic Nuclei / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate