The amygdala is critical for seizure propagation from brainstem to forebrain.
Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.
Hirsch
E
E
INSERM U 398, Faculté de Médecine, Strasbourg, France.
Danober
L
L
Simler
S
S
Pereira de Vasconcelos
A
A
Maton
B
B
Nehlig
A
A
Marescaux
C
C
Vergnes
M
M
D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D002250:Carbon Radioisotopes; D003847:Deoxyglucose; D004558:Electric Stimulation; D004569:Electroencephalography; D007696:Kindling, Neurologic / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D016548:Prosencephalon / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology*
D000779:Anesthetics, Local; D002250:Carbon Radioisotopes; D016760:Proto-Oncogene Proteins c-fos; D008012:Lidocaine; D003847:Deoxyglucose