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Disruption of plasticity mechanisms is increasingly recognized as a unifying feature of age\u2010related neurodegenerative and neuropsychiatric disorders. While classical models of long\u2010term potentiation (LTP) and long\u2010term depression (LTD) have primarily emphasized ionotropic glutamate receptors (iGluRs), emerging evidence identifies metabotropic glutamate receptors (mGluRs) as central regulators of synaptic stability, metaplasticity, and activity\u2010dependent translational control. This review synthesizes molecular, synaptic, circuit\u2010level, and translational evidence to position mGluR\u2013dependent plasticity as a context\u2010sensitive signaling framework that governs excitatory\u2013inhibitory balance across cortical and subcortical networks. This review examines subtype\u2010specific contributions of Groups I, II, and III mGluRs to LTP and LTD, highlighting their roles in intracellular calcium dynamics, protein synthesis\u2013dependent plasticity, and neuron\u2013glia interactions. Particular emphasis is placed on receptor localization, intracellular signaling pathways, and region\u2010specific cortical plasticity, which collectively determine how mGluR signaling shapes functional outcomes across distributed brain circuits. This review further discusses how dysregulation of mGluR\u2013mediated plasticity contributes to synaptic and circuit dysfunction in Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), schizophrenia, autism spectrum disorder (ASD), Fragile X syndrome (FXS), and epilepsy, with attention to disease stage\u2013specific and context\u2010dependent alterations revealed by electrophysiological, molecular, and receptor imaging studies. Finally, emerging translational strategies, including subtype\u2010selective biomarkers, allosteric and pathway\u2010biased modulation, and circuit\u2010targeted interventions, are evaluated for their potential to restore adaptive plasticity while limiting maladaptive network remodeling. Collectively, this review reframes mGluR\u2013dependent synaptic plasticity as a dynamic and integrative regulator of neuronal circuit function in aging and disease, providing a conceptual and mechanistic foundation for the development of precision neuroplasticity\u2010based therapeutics.<\/jats:p>","DOI":"10.1155\/np\/3455379","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:31:27Z","timestamp":1778823087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabotropic Glutamate Receptor\u2013Dependent Synaptic Plasticity in Age\u2010Related Neurodegenerative 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