What is GABAergic inhibition? How is it modified in epilepsy?

A deficit of gamma-aminobutyric acid-ergic (GABAergic) inhibition is hypoth esized to underlie most forms of epilepsy. Although apparently a straightfo rward and logical hypothesis to test, the search for a deficit of GABAergic inhibition in epileptic tissue has revealed itself to be as difficult as t he quest for the Holy Grail. The investigator faces many obstacles, includi ng the multiplicity of GABAergic inhibitory pathways and the multiplicity o f variables that characterize the potency of inhibition within each inhibit ory pathway. Perhaps more importantly, there seems to be no consensual defi nition of GABAergic inhibition. The first goal of this review is to try to clarify the notion of GABAergic inhibition. The second goal is to summarize our current knowledge of the various alterations that occur in the GABAerg ic pathways in temporal lobe epilepsy. Two important features will emerge: (a) according to the variable used to measure GABAergic inhibition, it may appear increased, decreased, or unchanged; and (b) these modifications are brain area- and inhibitory pathway-specific. The possible functional conseq uences of these alterations are discussed.