GABA(A) receptors, gephyrin and homeostatic synaptic plasticity.
Homeostatic synaptic plasticity describes the changes in synapse gain and function that occur in response to global changes in neuronal activity to maintain the stability of neuronal networks. In this review, we argue that a coordinated regulation of excitatory and inhibitory synaptic transmission is essential for maintaining CNS function while allowing both global and local changes in synaptic strength and connectivity. Therefore, we postulate that homeostatic synaptic plasticity depends on signalling cascades regulating in parallel the efficacy of glutamatergic and GABAergic transmission. Since neurotransmitter receptors interact closely with scaffolding proteins in the postsynaptic density, this coordinated regulation of excitatory and inhibitory synaptic transmission probably involves posttranslational modifications of scaffolding proteins, which in turn modulate local synaptic function. Here we review the current state of knowledge on the regulation of GABA(A) receptors and their main scaffolding protein gephyrin by posttranslational modifications; we outline future lines of research that might contribute to furthering our understanding of the molecular mechanisms regulating GABAergic synapse function and homeostatic plasticity.
Tyagarajan
Shiva K
SK
University of Zurich, Institute of Pharmacology and Toxicology, Winterhurerstrasse 190, CH-8057 Zurich, Switzerland.
Fritschy
Jean-Marc
JM
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D002352:Carrier Proteins; D008565:Membrane Proteins; D011963:Receptors, GABA-A; C073441:gephyrin