ArticleProceedings of the National Academy of Sciences of the United States of America2006
GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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Who cites it
199 citing papers in PubMed, 311 citations in OpenAlex.
- Slow wave sleep enhancement with gaboxadol reduces daytime sleepiness during sleep restriction.Sleep · 2008Trial
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- Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABABrain research · 2025Article
- Ethanol-induced rapid eye movement sleep suppression in rats: Comparison with subtype-selective GABAJournal of psychopharmacology (Oxford, England) · 2025Article
- Computational modeling of frequency-dependent neocortical response to thalamic neurostimulation in epilepsy.PLoS computational biology · 2025Article
- GLP-1 selectively enhances tonic GABAFrontiers in cellular neuroscience · 2025Article
- The PDE4 inhibitor apremilast modulates ethanol responses in Gabrb1-S409A knock-in mice via PKA-dependent and independent mechanisms.Neuropharmacology · 2024Article
- Generation of Astrocyte-specific BEST1 Conditional Knockout Mouse with Reduced Tonic GABA Inhibition in the Brain.Experimental neurobiology · 2024Article
- De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.European journal of human genetics : EJHG · 2024Article
- Manipulation of α4βδ GABABrain research · 2024Article
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
- Extrasynaptic δGABAA receptors mediate resistance to migraine-like phenotype in rats.The journal of headache and pain · 2024Article
- Enhancing GABAergic Tonic Inhibition Reduces Seizure-Like Activity in the Neonatal Mouse Hippocampus and Neocortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Mutation of novel ethanol-responsive lncRNA Gm41261 impacts ethanol-related behavioral responses in mice.Genes, brain, and behavior · 2024Article
- The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons.Current research in neurobiology · 2024Article
- Sex differences in motor learning flexibility are accompanied by sex differences in mushroom spine pruning of the mouse primary motor cortex during adolescence.Frontiers in neuroscience · 2024Article
- Nature's Own Pharmacy: Mushroom-Based Chemical Scaffolds and Their Therapeutic Implications.International journal of molecular sciences · 2023Review
- Cyclin D1-Cdk4 regulates neuronal activity through phosphorylation of GABAA receptors.Cellular and molecular life sciences : CMLS · 2023Article
- α4-Containing GABAeNeuro · 2023Article
139 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The neurotransmitter GABA mediates the majority of rapid inhibition in the CNS. Inhibition can occur via the conventional mechanism, the transient activation of subsynaptic GABAA receptors (GABAA-Rs), or via continuous activation of high-affinity receptors by low concentrations of ambient GABA, leading to "tonic" inhibition that can control levels of excitability and network activity. The GABAA-R alpha4 subunit is expressed at high levels in the dentate gyrus and thalamus and is suspected to contribute to extrasynaptic GABAA-R-mediated tonic inhibition. Mice were engineered to lack the alpha4 subunit by targeted disruption of the Gabra4 gene. alpha4 Subunit knockout mice are viable, breed normally, and are superficially indistinguishable from WT mice. In electrophysiological recordings, these mice show a lack of tonic inhibition in dentate granule cells and thalamic relay neurons. Behaviorally, knockout mice are insensitive to the ataxic, sedative, and analgesic effects of the novel hypnotic drug, gaboxadol. These data demonstrate that tonic inhibition in dentate granule cells and thalamic relay neurons is mediated by extrasynaptic GABAA-Rs containing the alpha4 subunit and that gaboxadol achieves its effects via the activation of this GABAA-R subtype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.