ArticleCerebral cortex (New York, N.Y. : 1991)2018
mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks.
Article in Cerebral cortex (New York, N.Y. : 1991), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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The trial behind it
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Who cites it
76 citing papers in PubMed, 110 citations in OpenAlex.
- Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.Molecular psychiatry · 2022Trial
- Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid-β Production and Cognitive Dysfunctions in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The mGluR2/3 agonist xanthurenic acid improves memory, attention, and synaptic deficits by modulating glutamate release in Alzheimer's disease model.Acta pharmacologica Sinica · 2026Article
- Identifying drug targets for schizophrenia through gene prioritization.Translational psychiatry · 2026Article
- A general one-step protocol to generate impermeable fluorescent HaloTag substrates for in situ live cell application and super-resolution imaging.Nature communications · 2026Article
- Targeting NAAG metabolism restores cognition and synaptic integrity in EcoHIV-infected mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Region-specific proteomic analysis of aging rhesus macaques following chronic glutamate-carboxypeptidase-II (GCPII) inhibition elucidates potential treatment strategies for sporadic Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Targeting metabotropic glutamate receptors for symptomatic and disease-modifying treatment in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Implicating neuroinflammation in hippocampus, prefrontal cortex and amygdala with cognitive deficit: a narrative review.3 Biotech · 2025Review
- mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy.Frontiers in bioscience (Landmark edition) · 2025Review
- Agonism at mGluR2 receptors reduces dysfunctional checking on a rodent analogue of compulsive-like checking in obsessive compulsive disorder.Psychopharmacology · 2025Article
- Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons.Journal of neurochemistry · 2025Article
- Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.Biological psychiatry · 2025Review
- Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.Current neuropharmacology · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Exploration of Key Genes and Molecular Mechanisms in Mice with Perioperative Neurocognitive Disorders Treated with Remimazolam Based on Transcriptomics and Experimental Verification.Drug design, development and therapy · 2025Article
- Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation.Frontiers in aging neuroscience · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K+ channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission. We have discovered that, in addition to their astrocytic expression, mGluR3 is concentrated postsynaptically in spine synapses of layer III dlPFC, positioned to strengthen connectivity by inhibiting postsynaptic cAMP-K+ channel actions. In contrast, mGluR2 is principally presynaptic as expected, with only a minor postsynaptic component. Functionally, increase in the endogenous mGluR3 agonist, N-acetylaspartylglutamate, markedly enhanced dlPFC Delay cell firing during a working memory task via inhibition of cAMP signaling, while the mGluR2 positive allosteric modulator, BINA, produced an inverted-U dose-response on dlPFC Delay cell firing and working memory performance. These data illuminate why insults to mGluR3 would erode cognitive abilities, and support mGluR3 as a novel therapeutic target for higher cognitive 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.