title: Role of GABAAR trafficking in the plasticity of inhibitory synapses.
abstract: Neuronal excitability depends on the balance between inhibitory and excitatory neurotransmission, which in the CNS are mainly mediated by GABA and glutamate respectively. The plasticity of glutamatergic synapses and the underlying molecular mechanisms have been characterized to a large extent. In comparison, much less is known regarding the plasticity of GABAergic synapses, which is also important in the maintenance of the excitatory/inhibitory balance. GABAergic synapses, similarly to the glutamatergic synapses, adjust their strength depending on the pattern of neuronal activity. These alterations take place in the pre- and postsynaptic compartments, and short- and long-term alterations have been described. At the postsynaptic level the plasticity of inhibitory synapses is largely mediated by modulation of the expression, localization and function of GABAAreceptors, by mechanisms involving the participation of scaffold proteins and structural molecules. This review is focused on the key mechanisms that regulate GABAAreceptor trafficking in response to alterations in neuronal activity or to stimulation of plasma membrane receptors. These alterations in GABAergic neurotransmission are important in the refinement of the pattern of activity of neuronal networks. In this work, we review some of the mechanisms contributing to the plasticity of inhibitory synapses in the CNS, focusing on the regulation of GABAAreceptor (GABAAR) trafficking in response to alterations in neuronal activity or to stimulation of different classes of plasma membrane-associated receptors. Alterations in these mechanisms are important in the refinement of neuronal network activity. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Miranda
authors.initials: M
authors.lastname: Mele
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Graciano
authors.initials: G
authors.lastname: Leal
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Duarte
mesh_terms: D000818:Animals; D059330:GABAergic Neurons / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A
keywords: GABAA receptors; gephyrin; intracellular traffic; synapse; synaptic regulation