TY - JOUR T1 - Modulation of Absence Seizures by the GABA<sub>A</sub> Receptor: A Critical Role for Metabotropic Glutamate Receptor 4 (mGluR4) JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6218 LP - 6224 DO - 10.1523/JNEUROSCI.20-16-06218.2000 VL - 20 IS - 16 AU - O. Carter Snead III AU - P. K. Banerjee AU - McIntyre Burnham AU - David Hampson Y1 - 2000/08/15 UR - http://www.jneurosci.org/content/20/16/6218.abstract N2 - Experimental absence seizures are associated with perturbations in the presynaptic release of GABA and glutamate within thalamocortical circuitry. The release of both glutamate and GABA is regulated by group III metabotropic glutamate receptors (mGluRs). Therefore, we examined the susceptibility of mice lacking the mGluR4 subtype of mGluR (mGluR4−/−) versus their wild-type controls (mGluR4+/+) to absence seizures induced either by γ-hydroxybutyrate (GHB) or the GABABagonist (−) baclofen or by low doses of the GABAA receptor (GABAAR) antagonists pentylenetetrazole, bicuculline, or picrotoxin. There was no difference between mGluR4−/− and mGluR4+/+ mice in threshold to absence seizures induced by either GHB or (−) baclofen. In contrast, the mGluR4−/− mice were markedly resistant to absence seizures induced by low doses of GABAAR antagonists. No differences were observed between mGluR4−/− and mGluR4+/+ mice in threshold to clonic or tonic seizures induced by higher doses of GABAAR antagonists, strychnine, or electroshock, indicating that seizure resistance in the mGluR4−/− mice was restricted solely to absence seizures. The resistance of mGluR4−/− mice to absence seizures induced by GABAAR antagonists was mimicked by bilateral administration of a mGluR4 antagonist into the nucleus reticularis thalami (nRT) of mGluR4+/+ mice. Conversely, intra-nRT administration of a mGluR4 agonist in mGluR4+/+ mice exacerbated GABAAR-induced absence seizures. These data indicate that the presence of mGluR4 within nRT is critical to GABAergic modulation of thalamocortical synchronization in normal and pathological states, such as generalized absence epilepsy. ER -