title: The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type.
abstract: The diversity of GABAA receptor (GABAAR) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance. The specific functions of tonic versus phasic GABAergic inhibition in different cell types and the impact on specific neural circuits are only beginning to be unraveled. Here we review the diversity in the magnitude of tonic GABAergic inhibition in various brain regions and cell types, and highlight the impact on neuronal excitability in different neuronal circuits. Further, we discuss the relevance of tonic inhibition in various physiological and pathological contexts as well as the potential of targeting these receptor subtypes for treatment of diseases, such as epilepsy.
authors.affiliation: Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University Boston, MA, USA.
authors.forename: Vallent
authors.initials: V
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine Boston, MA, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Maguire
mesh_terms: D001921:Brain / Q000502:physiology*; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid
keywords: GABA; epilepsy; neuronal excitability; neurosteroids; tonic inhibition