Metabotropic glutamate receptors in the thalamocortical network: Strategic targets for the treatment of absence epilepsy

Metabotropic glutamate (mGlu) receptors are positioned at synapses of the thalamocortical network that underlie the development of spike-and-wave discharges (SWDs) associated with absence epilepsy. The modulatory role of individual mGlu receptor subtypes on excitatory and inhibitory synaptic transmission in the cortico-thalamo-cortical circuitry makes subtype-selective mGlu receptor ligands potential candidates as novel antiabsence drugs. Some of these compounds are under clinical development for the treatment of numerous neurologic and psychiatric disorders, and might be soon available for clinical studies in patients with absence seizures refractory to conventional medications. Herein we review the growing evidence that links mGlu receptors to the pathophysiology of pathologic SWDs moving from the anatomic localization and function of distinct mGlu receptor subtypes in the cortico-thalamo-cortical network to in vivo studies in mouse and rat models of absence epilepsy.