ArticleProceedings of the National Academy of Sciences of the United States of America2025
Spontaneous glutamate release activates mGluR signaling to drive rapid antidepressant responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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.
The trial behind it
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Who cites it
3 citing papers in PubMed.
- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 2026Article
- Impact of distinct neurotransmitter release modes on neuronal signaling.Molecular psychiatry · 2026Review
- The Relationship Between Trace Elements and Depression.Nutrients · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects. We show that enhancing the endogenous mGluR5 signaling produces synaptic potentiation in the hippocampus and triggers the rapid antidepressant effect, similar to ketamine. Importantly, blocking mGluR5 prevents ketamine's effects, revealing a synergy between the two pathways. At the cellular level, spontaneous calcium transients mediated by mGluR5 activate the phosphatase calcineurin and promote eukaryotic elongation factor 2 (eEF2) dephosphorylation, increasing BDNF translation to drive synaptic plasticity. We show that quantal glutamate release activates two spatially segregated Ca
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