ArticleNeuron2014
A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed.
- Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis.The international journal of neuropsychopharmacology · 2026Trial
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- GATOR1 signaling defects promote astrocytic metabolic rewiring and excitatory neurotransmitter cycling.EMBO reports · 2026Article
- The Role of the Glutamate-Glutamine Cycle in Synaptic Transmission During Ischemia and Recovery.The European journal of neuroscience · 2026Article
- Glutamine synthetase sustains cortical circuit development via mTOR-mediated astrocyte maturation.Protein & cell · 2026Article
- Uncovering the Key Circuit FOSL2/FOS/EGR3/EGR1, Contributing to the Hyperexcitability of Excitatory Neurons in the Epileptic Temporal Cortex and Hippocampus.International journal of molecular sciences · 2026Article
- Translatome profiling of spinal cord astrocytes reveals distinct gene signatures associated with acute and chronic pain.iScience · 2026Article
- Neurotoxic Effects of Acute Tributyltin Exposure in Adult Zebrafish: Behavioral Impairments and Mechanistic Insights.Metabolites · 2026Article
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Microglia-astrocyte crosstalk as a key organizing principle of Alzheimer's disease: from homeostatic cooperation to maladaptive signaling loops.Frontiers in aging neuroscience · 2026Review
- Olive oil-derived monounsaturated fat influences metabolic signatures in serotonergic regions of the brain in broiler chicken.Frontiers in physiology · 2026Article
- Sustained hippocampal neuroinflammation and subsequent glutamatergic dysfunction in juvenile idiopathic arthritis: evidence from proton magnetic resonance spectroscopy (Arthritis research & therapy · 2025Article
- Emerging roles of astrocytes in autonomic control of blood pressure and hypertension.American journal of physiology. Cell physiology · 2025Review
- The Crosstalk Between Brain Energy Metabolism and Neuropathic Pain: Mechanisms and Therapeutic Implications.Metabolites · 2025Review
- Histone Deacetylases in Neurodegenerative Diseases and Their Potential Role as Therapeutic Targets: Shedding Light on Astrocytes.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dynamic Intercellular Networks in the CNS: Mechanisms of Crosstalk from Homeostasis to Neurodegeneration.International journal of molecular sciences · 2025Review
- Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies.Cancer metastasis reviews · 2025Review
- Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop.Cell death and differentiation · 2025Article
- The Role of Astrocytes in Synaptic Dysfunction and Memory Deficits in Alzheimer's Disease.Biomolecules · 2025Review
- Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance.Molecular oncology · 2025Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Biochemical studies suggest that excitatory neurons are metabolically coupled with astrocytes to generate glutamate for release. However, the extent to which glutamatergic neurotransmission depends on this process remains controversial because direct electrophysiological evidence is lacking. The distance between cell bodies and axon terminals predicts that glutamine-glutamate cycle is synaptically localized. Hence, we investigated isolated nerve terminals in brain slices by transecting hippocampal Schaffer collaterals and cortical layer I axons. Stimulating with alternating periods of high frequency (20 Hz) and rest (0.2 Hz), we identified an activity-dependent reduction in synaptic efficacy that correlated with reduced glutamate release. This was enhanced by inhibition of astrocytic glutamine synthetase and reversed or prevented by exogenous glutamine. Importantly, this activity dependence was also revealed with an in-vivo-derived natural stimulus both at network and cellular levels. These data provide direct electrophysiological evidence that an astrocyte-dependent glutamate-glutamine cycle is required to maintain active neurotransmission at excitatory terminals.
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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.