ArticleNature communications2018
Higher ambient synaptic glutamate at inhibitory versus excitatory neurons differentially impacts NMDA receptor activity.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
20 citing papers in PubMed, 44 citations in OpenAlex.
- GluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.Acta pharmacologica Sinica · 2026Article
- Characterizing Spatial Associations Between GluCEST MRI and Neurotransmitter Receptor Density in the Human Cortex.Human brain mapping · 2025Article
- Peripheral glia and neurons jointly regulate activity-induced synaptic remodeling at theeLife · 2025Article
- Enhancement of hippocampal interneuron excitability by NMDA receptor positive allosteric modulation.The Journal of physiology · 2025Article
- Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder.CNS drugs · 2024Review
- Pathological Interplay between Inflammation and Mitochondria Aggravates Glutamate Toxicity.International journal of molecular sciences · 2024Review
- Targeting synapse function and loss for treatment of neurodegenerative diseases.Nature reviews. Drug discovery · 2024Review
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Paraventricular Thalamus Dynamically Modulates Aversive Memory via Tuning Prefrontal Inhibitory Circuitry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders.Frontiers in molecular neuroscience · 2023Review
- Altered GABAInternational journal of molecular sciences · 2022Article
- Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction.Neural regeneration research · 2022Article
- Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia.Biomolecules · 2021Article
- Long-Term Enhancement of NMDA Receptor Function in Inhibitory Neurons Preferentially Modulates Potassium Channels and Cell Adhesion Molecules.Frontiers in pharmacology · 2021Article
- Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress.Frontiers in molecular neuroscience · 2021Article
- Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus.Scientific reports · 2020Article
- Elevated Level of PKMζ Underlies the Excessive Anxiety in an Autism Model.Frontiers in molecular neuroscience · 2019Article
- Control of Long-Term Plasticity by Glutamate Transporters.Frontiers in synaptic neuroscience · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective disruption of synaptic drive to inhibitory neurons could contribute to the pathophysiology of various brain disorders. We have previously identified a GluN2A-selective positive allosteric modulator, GNE-8324, that selectively enhances N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic responses in inhibitory but not excitatory neurons. Here, we demonstrate that differences in NMDAR subunit composition do not underlie this selective potentiation. Rather, a higher ambient glutamate level in the synaptic cleft of excitatory synapses on inhibitory neurons is a key factor. We show that increasing expression of glutamate transporter 1 (GLT-1) eliminates GNE-8324 potentiation in inhibitory neurons, while decreasing GLT-1 activity enables potentiation in excitatory neurons. Our results reveal an unsuspected difference between excitatory synapses onto different neuronal types, and a more prominent activation of synaptic NMDARs by ambient glutamate in inhibitory than excitatory neurons. This difference has implications for tonic NMDAR activity/signaling and the selective modulation of inhibitory neuron activity to treat brain disorders.
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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.