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PURPOSE OF REVIEW: While epilepsy describes a heterogeneous array of syndromes, the conventional view is that there is a common underlying failure in the ability of GABAergic inhibition to overcome excessive synaptic excitation. This review explores the possibility that enhanced GABAergic inhibition in the neocortex could also be proepileptogenic. RECENT FINDINGS: Recently, two mouse strains carrying mutant alleles of the alpha4 subunit of the nicotinic acetylcholine receptor that are associated with autosomal dominant nocturnal frontal lobe epilepsy have been found to show spontaneous seizures. Recordings from neocortical pyramidal neurons in vitro show that the autosomal dominant nocturnal frontal lobe epilepsy mutations are associated with large selective increases in nicotine-evoked GABAergic inhibition, which may be key factor in epileptogenesis, as the seizures in vivo are blocked by subconvulsive doses of the GABAA receptor antagonist, picrotoxin. SUMMARY: The precise links between the observed gain of neocortical inhibition and development of seizures in autosomal dominant nocturnal frontal lobe epilepsy mice remain unknown. Recent insights into the functional properties of cortical GABAergic circuits, however, suggest several possible pathways to be explored, whose elucidation could enable selective therapeutic interventions.

Original publication

DOI

10.1097/WCO.0b013e3282f52f5f

Type

Journal article

Journal

Curr Opin Neurol

Publication Date

04/2008

Volume

21

Pages

155 - 160

Keywords

Animals, Chromosome Disorders, Chronobiology Disorders, Disease Models, Animal, Epilepsy, Frontal Lobe, Frontal Lobe, Genes, Dominant, Humans, Mice, Neural Inhibition, Receptors, Nicotinic, gamma-Aminobutyric Acid