ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 109 citations in OpenAlex.
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- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 2026Article
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- In vivo mapping of protein-protein interactions of schizophrenia risk factors generates an interconnected disease network.Schizophrenia (Heidelberg, Germany) · 2026Article
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.Clinical science (London, England : 1979) · 2025Review
- Activation of Endoplasmic Reticulum-Localized Metabotropic Glutamate Receptor 5 (mGluBiomolecules · 2025Article
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- Enhanced mGluRCell death & disease · 2024Article
- Endosome positioning coordinates spatially selective GPCR signaling.Nature chemical biology · 2024Article
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.Science advances · 2023Article
- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- FGF21 modulates hippocampal cold-shock proteins and CA2-subregion proteins in neonatal mice with hypoxia-ischemia.Pediatric research · 2023Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder.Biological psychiatry · 2023Article
- Review
- A sex-specific genome-wide association study of depression phenotypes in UK Biobank.Molecular psychiatry · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Metabotropic glutamate receptor 5 (mGluR5) is widely expressed throughout the CNS and participates in regulating neuronal function and synaptic transmission. Recent work in the striatum led to the groundbreaking discovery that intracellular mGluR5 activation drives unique signaling pathways, including upregulation of ERK1/2, Elk-1 (Jong et al., 2009) and Arc (Kumar et al., 2012). To determine whether mGluR5 signals from intracellular membranes of other cell types, such as excitatory pyramidal neurons in the hippocampus, we used dissociated rat CA1 hippocampal cultures and slice preparations to localize and characterize endogenous receptors. As in the striatum, CA1 neurons exhibited an abundance of mGluR5 both on the cell surface and intracellular membranes, including the endoplasmic reticulum and the nucleus where it colocalized with the sodium-dependent excitatory amino acid transporter, EAAT3. Inhibition of EAAT3 or sodium-free buffer conditions prevented accumulations of radiolabeled agonist. Using a pharmacological approach to isolate different pools of mGluR5, both intracellular and cell surface receptors induced oscillatory Ca(2+) responses in dissociated CA1 neurons; however, only intracellular mGluR5 activation triggered sustained high amplitude Ca(2+) rises in dendrites. Consistent with the notion that mGluR5 can signal from intracellular membranes, uncaging glutamate on a CA1 dendrite led to a local Ca(2+) rise, even in the presence of ionotropic and cell surface metabotropic receptor inhibitors. Finally, activation of intracellular mGluR5 alone mediated both electrically induced and chemically induced long-term depression, but not long-term potentiation, in acute hippocampal slices. These data suggest a physiologically relevant and important role for intracellular mGluR5 in hippocampal synaptic plasticity.
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