ArticleThe Journal of physiology2013
A functional role for both -aminobutyric acid (GABA) transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 139 citations in OpenAlex.
- Hippocampal Astrocytes Impact Postnatal Development of Inhibitory Connections, Parvalbumin Levels, Social, and Spatial Navigation Behaviors in a Mouse Model of Fragile X Syndrome.Journal of neurochemistry · 2026Article
- Hippocampal astrocytic GAT-3 blockade impairs protein synthesis and spatial memory dynamics.Communications biology · 2026Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- microRNA-17-5p modulates ventral hippocampal transcriptome and synaptic proteome: Implications for emotional regulation in adult male rats.Neurobiology of disease · 2026Article
- Conditional knockout of Dkk3 drives Lgr5+ progenitor reprogramming into hair cells in the mouse cochlea.Theranostics · 2026Article
- Association of CYP3A4*1B and SLC6A11 Genetic Variants with Epilepsy Risk And Antiepileptic Drug Response in an Iraqi Population.Molecular neurobiology · 2025Article
- Article
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Astrocytic modulation of population encoding in mouse visual cortex via GABA transporter 3 revealed by multiplexed CRISPR/Cas9 gene editing.bioRxiv : the preprint server for biology · 2025Article
- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Astroglia's role in synchronized spontaneous neuronal activity: from physiology to pathology.Frontiers in cellular neuroscience · 2025Review
- Role of the STING→IRF3 Pathway in Ambient GABA Homeostasis and Cognitive Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles.Cell research · 2024Article
- Brain Gene Regulatory Networks Coordinate Nest Construction in Birds.Molecular biology and evolution · 2024Article
- Fast-spiking parvalbumin-positive interneurons in brain physiology and Alzheimer's disease.Molecular psychiatry · 2023Review
- GABA tone regulation and its cognitive functions in the brain.Nature reviews. Neuroscience · 2023Review
- Impact of Developmental Changes of GABAInternational journal of molecular sciences · 2023Article
- A Diet Enriched withInternational journal of molecular sciences · 2023Article
- Astrocyte expression in the extended amygdala of C57BL/6J mice is sex-dependently affected by chronic intermittent and binge-like ethanol exposure.Alcohol (Fayetteville, N.Y.) · 2023Article
- Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network.Current biology : CB · 2023Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Tonic γ-aminobutyric acid (GABA)A receptor-mediated signalling controls neuronal network excitability in the hippocampus. Although the extracellular concentration of GABA (e[GABA]) is critical in determining tonic conductances, knowledge on how e[GABA] is regulated by different GABA transporters (GATs) in vivo is limited. Therefore, we studied the role of GATs in the regulation of hippocampal e[GABA] using in vivo microdialysis in freely moving rats. Here we show that GAT-1, which is predominantly presynaptically located, is the major GABA transporter under baseline, quiescent conditions. Furthermore, a significant contribution of GAT-3 in regulating e[GABA] was revealed by administration of the GAT-3 inhibitor SNAP-5114 during simultaneous blockade of GAT-1 by NNC-711. Thus, the GABA transporting activity of GAT-3 (the expression of which is confined to astrocytes) is apparent under conditions in which GAT-1 is blocked. However, sustained neuronal activation by K(+)-induced depolarization caused a profound spillover of GABA into the extrasynaptic space and this increase in e[GABA] was significantly potentiated by sole blockade of GAT-3 (i.e. even when uptake of GAT-1 is intact). Furthermore, experiments using tetrodotoxin to block action potentials revealed that GAT-3 regulates extrasynaptic GABA levels from action potential-independent sources when GAT-1 is blocked. Importantly, changes in e[GABA] resulting from both GAT-1 and GAT-3 inhibition directly precipitate changes in tonic conductances in dentate granule cells as measured by whole-cell patch-clamp recording. Thus, astrocytic GAT-3 contributes to the regulation of e[GABA] in the hippocampus in vivo and may play an important role in controlling the excitability of hippocampal cells when network activity is increased.
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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.