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GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system.

  • Fritschy JM Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland.
  • Panzanelli P
  • 2014-03-18
Published in:
  • The European journal of neuroscience. - 2014
diazepam
excitatory-inhibitory balance
gephyrin
neurogenesis
phosphorylation
postsynaptic density
Animals
Central Nervous System
GABAergic Neurons
Humans
Inhibitory Postsynaptic Potentials
Neurogenesis
Neuronal Plasticity
Protein Multimerization
Protein Transport
Receptors, GABA-A
English GABAA receptors (GABAA Rs) are ligand-gated Cl(-) channels that mediate most of the fast inhibitory neurotransmission in the central nervous system (CNS). Multiple GABAA 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 GABAA 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. GABAA 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 GABAA Rs, but also modifying the postsynaptic scaffold organised by gephyrin to anchor specific receptor subtypes at postsynaptic sites. The significance of GABAA 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 GABAA R subtypes reveals their involvement in the pathophysiology of major CNS disorders, and opens novel perspectives for therapeutic intervention. In conclusion, GABAA 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.
Language
  • English
Open access status
green
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https://folia.unifr.ch/global/documents/102977
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