AUTHOR=Fritschy Jean-Marc 

TITLE=Epilepsy, E/I balance and GABA<sub>A</sub> receptor plasticity

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 1 - 2008

YEAR=2008

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/neuro.02.005.2008

DOI=10.3389/neuro.02.005.2008

ISSN=1662-5099

ABSTRACT=GABA<sub>A</sub> receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABA<sub>A</sub> receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fi ne-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABA<sub>A</sub> receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I) balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent fi ndings highlighting the signifi cance of GABA<sub>A</sub> receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifi cally, we address the following issues: (1) role for tonic inhibition, mediated by extrasynaptic GABA<sub>A</sub> receptors, for controlling neuronal excitability; (2) signifi cance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3) molecular mechanisms underlying GABA<sub>A</sub> receptor regulation (traffi cking, posttranslational modifi cation, gene transcription) that are important for homoeostatic plasticity. Finally, the relevance of these fi ndings is discussed in light of the involvement of GABA<sub>A</sub> receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE) and absence seizures and on the identifi cation of mutations in GABA<sub>A</sub> receptor subunit genes underlying familial forms of epilepsy.