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GABA A receptors and plasticity of inhibitory neurotransmission in the central nervous system
Author(s) -
Fritschy JeanMarc,
Panzanelli Patrizia
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12534
Subject(s) - gephyrin , neurotransmission , neuroscience , postsynaptic potential , inhibitory postsynaptic potential , biology , gabaa receptor , synaptic plasticity , long term potentiation , receptor , neurogenesis , glycine receptor , genetics , amino acid , glycine
GABA A receptors ( GABA A R s) are ligand‐gated Cl − channels that mediate most of the fast inhibitory neurotransmission in the central nervous system ( CNS ). Multiple GABA A R subtypes are assembled from a family of 19 subunit genes, raising the question of the significance of this heterogeneity. In this review, we discuss the evidence that GABA A R subtypes represent distinct receptor populations with a specific spatio‐temporal expression pattern in the developing and adult CNS , being endowed with unique functional and pharmacological properties, as well as being differentially regulated at the transcriptional, post‐transcriptional and translational levels. GABA A R subtypes are targeted to specific subcellular domains to mediate either synaptic or extrasynaptic transmission, and their action is dynamically regulated by a vast array of molecular mechanisms to adjust the strength of inhibition to the changing needs of neuronal networks. These adaptations involve not only changing the gating or kinetic properties of GABA A R s, but also modifying the postsynaptic scaffold organised by gephyrin to anchor specific receptor subtypes at postsynaptic sites. The significance of GABA A R heterogeneity is particularly evident during CNS development and adult neurogenesis, with different receptor subtypes fulfilling distinct steps of neuronal differentiation and maturation. Finally, analysis of the specific roles of GABA A R subtypes reveals their involvement in the pathophysiology of major CNS disorders, and opens novel perspectives for therapeutic intervention. In conclusion, GABA A R subtypes represent the substrate of a multifaceted inhibitory neurotransmission system that is dynamically regulated and performs multiple operations, contributing globally to the proper development, function and plasticity of the CNS .