Amygdaloid kindling in glutamate transporter (GLAST) knockout mice.
OBJECTIVE
Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system. We previously reported abnormal glutamate release during seizures after kindling. GLAST and GLT-1 are astrocytic glutamate transporters, highly concentrated in the cerebellum and the telencephalon, respectively. We have investigated whether stages of amygdala kindling in knockout (KO) mice deficient in GLAST are the same as those of wild mice.


METHODS
Electrodes were implanted into the basolateral amygdala, bilaterally, in C57BL/6J mice and GLAST KO mice under anesthesia. Once-daily stimulation was applied on one side through these electrodes, and bilateral EEG recordings were obtained.


RESULTS
The behavioral manifestations of kindling in mice were (a) arrest of behavior, (b) head nodding, (c) forelimb clonus, (d) bilateral forelimb clonus with rearing, (e) tonic generalized convulsion with elevation of tail and falling with generalized tonic convulsion (GTC). Results of kindling: (a) Mutant mice kindled more slowly than wild-type mice (more stimulations were required to reach each stage in mutants); (b) after kindling was completed, additional stimulations induced shorter afterdischarges (ADs) in mutants than in wild-type mice; (c) Interictal epileptic spikes were more frequent in the mutants than in the wild-type mice, both in the stimulated amygdala and in the contralateral amygdala.


CONCLUSIONS
GLAST KO mice, which are missing one type of astrocytic glutamate transporter, demonstrate kindling of an epileptic focus. However, the kindling is significantly slower in the GLAST mutant than in wild-type mice. These findings suggest that glutamate transport by the astrocytic GLAST transporter may have a role in normal epileptogenesis.
Departmens of Psychology, Miyazaki Medical College, Miyazaki, Japan. tsuru@post1.miyazaki-med.ac.jp
Noriko
N
Tsuru
Yuto
Y
Ueda
Taku
T
Doi
D000200:Action Potentials; D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000502:physiology*; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004569:Electroencephalography; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D012016:Reference Values
D027322:Amino Acid Transport System X-AG