ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Dynamic regulation of synaptic GABA release by the glutamate-glutamine cycle in hippocampal area CA1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 207 citations in OpenAlex.
- Article
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- Sex-dependent preventive effects of prenatal N-acetyl-cysteine on neuronal, emotional and metabolic dysfunctions following exposure to maternal high-fat diet in mice.Translational psychiatry · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- The Glutamate/GABA-Glutamine Cycle: Insights, Updates, and Advances.Journal of neurochemistry · 2025Review
- Emerging roles of astrocytes in hippocampal circuitry and behavior.Frontiers in cellular neuroscience · 2025Review
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.bioRxiv : the preprint server for biology · 2024Article
- Distinct GABAergic modulation of timing-dependent LTP in CA1 pyramidal neurons along the longitudinal axis of the mouse hippocampus.iScience · 2024Article
- The role of glutamate and glutamine metabolism and related transporters in nerve cells.CNS neuroscience & therapeutics · 2024Review
- The properties of long-term potentiation at SC-CA1/ TA-CA1 hippocampal synaptic pathways depends upon their input pathway activation patterns.IBRO neuroscience reports · 2023Article
- Glial Glutamine Homeostasis in Health and Disease.Neurochemical research · 2023Review
- Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice.Translational psychiatry · 2023Article
- Astrocyte metabolism and signaling pathways in the CNS.Frontiers in neuroscience · 2023Review
- AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease.International journal of molecular sciences · 2022Review
- Dysregulation of Astrocytic Glutamine Transport in Acute Hyperammonemic Brain Edema.Frontiers in neuroscience · 2022Review
- Article
- Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Hippocampal astrocytic neogenin regulating glutamate uptake, a critical pathway for preventing epileptic response.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Vesicular GABA and intraterminal glutamate concentrations are in equilibrium, suggesting inhibitory efficacy may depend on glutamate availability. Two main intraterminal glutamate sources are uptake by neuronal glutamate transporters and glutamine synthesized through the astrocytic glutamate-glutamine cycle. We examined the involvement of the glutamate-glutamine cycle in modulating GABAergic synaptic efficacy. In the absence of neuronal activity, disruption of the glutamate-glutamine cycle by blockade of neuronal glutamine transport with alpha-(methylamino) isobutyric acid (MeAIB; 5 mM) or inhibition of glutamine synthesis in astrocytes with methionine sulfoximine (MSO; 1.5 mM) had no effect on miniature IPSCs recorded in hippocampal area CA1 pyramidal neurons. However, after a period of moderate synaptic activity, application of MeAIB, MSO, or dihydrokainate (250 microM; an astrocytic glutamate transporter inhibitor) significantly reduced evoked IPSC (eIPSC) amplitudes. The MSO effect could be reversed by exogenous application of glutamine (5 mM), whereas glutamine could not rescue the eIPSC decreases induced by the neuronal glutamine transporter inhibitor MeAIB. The activity-dependent reduction in eIPSCs by glutamate-glutamine cycle blockers was accompanied by an enhanced blocking effect of the low-affinity GABA(A) receptor antagonist, TPMPA [1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid], consistent with diminished GABA release. We further corroborated this hypothesis by examining MeAIB effects on minimal stimulation-evoked quantal IPSCs (meIPSCs). We found that, in MeAIB-containing medium, moderate stimulation induced depression in potency of meIPSCs but no change in release probability, consistent with reduced vesicular GABA content. We conclude that the glutamate-glutamine cycle is a major contributor to synaptic GABA release under physiological conditions, which dynamically regulates inhibitory synaptic strength.
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Registered trials
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.