ArticleBMC biology2012
Astrocytes convert network excitation to tonic inhibition of neurons.
Article in BMC biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 169 citations in OpenAlex.
- Controlling Epileptic Activity by Modulating Putrescine Metabolism.Biomolecules · 2026Article
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- 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
- Scyllo-Inositol as a Neuroactive Agent: From Pharmacokinetics to Neuroprotective and Antiepileptic Effects.Nutrients · 2026Review
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- Modular Model of Neuronal Activity That Captures the Dynamics of Main Molecular Targets of Antiepileptic Drugs.International journal of molecular sciences · 2026Article
- Calcium Imaging Studies in Enteric Glia.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Emerging roles of astrocytes in autonomic control of blood pressure and hypertension.American journal of physiology. Cell physiology · 2025Review
- Article
- Dynamic and Homeostatic Neuron-Astrocyte Interactions at GABAergic Synapses.Neurochemical research · 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
- Optogenetic inhibition of ventrolateral orbitofrontal cortex astrocytes facilitates ventrolateral periaqueductal gray glutamatergic activity to reduce hypersensitivity in infraorbital nerve injury rat model.The journal of headache and pain · 2025Article
- Glutamate/GABA/glutamine ratios in intact and ischemia reperfusion challenged rat brain subregions, the effect of ischemic preconditioning.Metabolic brain disease · 2025Article
- Nitrogen waste metabolism as a locus of nitrergic co-transmission in the brain.Frontiers in behavioral neuroscience · 2025Review
- FluoAnalysis: An Open-Source MATLAB Toolbox for Analysis of Calcium Imaging Measurements of Oscillatory Astrocytic and Neuronal Networks.Brain sciences · 2024Article
- Gene therapy for Lafora disease in the Epm2aMolecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.
resultsHere we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na+ concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg2+] in vitro model of epilepsy. Under in vivo conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.
conclusionsThe results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamatergic excitation into GABAergic inhibition providing an adjustable, in situ negative feedback on the excitability of neurons.
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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.