Altered glutamate and GABA release within thalamocortical circuitry in metabotropic glutamate receptor 4 knockout mice.
The metabotropic glutamate receptor 4 is highly expressed presynaptically on thalamocortical neurons that are involved in the pathogenesis of generalized absence seizures. Mutant mice devoid of metabotropic glutamate receptor 4 are completely resistant to absence seizures induced by low doses of GABA type A receptor antagonists. The purpose of this study was to test the hypothesis that there is altered glutamate and GABA release within thalamocortical circuitry in mice devoid of metabotropic glutamate receptor 4. Extracellular GABA and glutamate release were determined in ventrobasal thalamus, the nucleus reticularis thalami and laminae I-III, and IV-VI of cerebral cortex (laminae I-III of cerebral cortex, and laminae IV-VI of cerebral cortex) using in vivo microdialysis techniques on awake, free moving mice. A significant increase of both basal and K(+)-evoked glutamate release was detected in the ventrobasal thalamus, the nucleus reticularis thalami and laminae IV-VI of cerebral cortex of mice devoid of metabotropic glutamate receptor 4 mice. There also was a significant increase in both basal and K(+)-evoked GABA release in the mice devoid of metabotropic glutamate receptor 4, but a significant decrease of GABA release in laminae IV-VI of cerebral cortex. However, there was no alteration of either GABA or glutamate release in laminae I-III of cerebral cortex, cortical laminae that are not involved in absence seizures. These data indicate that deletion of the metabotropic glutamate receptor 4 gene results in a selective perturbation of glutamate and GABA release within the thalamocortical circuitry involved in the pathogenesis of absence seizures.
Wang
X
X
Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
Ai
J
J
Hampson
D R
DR
Snead
O C
OC
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004832:Epilepsy, Absence / Q000503:physiopathology; D018698:Glutamic Acid / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency* / Q000235:genetics; D013788:Thalamus / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C108823:metabotropic glutamate receptor 4