Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures.
Typical absence has long been considered as the prototypic form of generalized nonconvulsive epileptic seizures. Recent investigations in patients and animal models suggest that absence seizures could originate from restricted regions of the cerebral cortex. However, the cellular and local network processes of seizure initiation remain unknown. Here, we show that absence seizures in Genetic Absence Epilepsy Rats from Strasbourg, a well established genetic model of this disease, arise from the facial somatosensory cortex. Using in vivo intracellular recordings, we found that epileptic discharges are initiated in layer 5/6 neurons of this cortical region. These neurons, which show a distinctive hyperactivity associated with a membrane depolarization, lead the firing of distant cortical cells during the epileptic discharge. Consistent with their ictogenic properties, neurons from this "focus" exhibit interictal and preictal oscillations that are converted into epileptic pattern. These results confirm and extend the "focal hypothesis" of absence epilepsy and provide a cellular scenario for the initiation and generalization of absence seizures.
Polack
Pierre-Olivier
PO
Institut National de la Santé et de la Recherche Médicale Unité 667, Collège de France, 75231 Paris, Cedex 05, France. pierre-olivier.polack@college-de-france.fr
Guillemain
Isabelle
I
Hu
Emilie
E
Deransart
Colin
C
Depaulis
Antoine
A
Charpier
Stéphane
S
D000200:Action Potentials / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001931:Brain Mapping; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005145:Face / Q000294:innervation; D008957:Models, Genetic; D009474:Neurons / Q000145:classification / Q000502:physiology*; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000473:pathology*; D014851:Wakefulness / Q000502:physiology
C070614:neurobiotin; D001710:Biotin