{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The GRIN3A gene encodes the GluN3A subunit of N‐methyl‑D‑aspartate (NMDA) receptors, which functions as an atypical modulatory element in glutamatergic neurotransmission. GluN3A incorporation into NMDA receptors reduces channel calcium permeability and current amplitude, thereby acting as a “molecular brake” on synaptic maturation. During early postnatal development, high levels of GluN3A help prevent premature strengthening and stabilization of excitatory synapses; its subsequent downregulation is necessary for full long‐term potentiation, proper spine stabilization, and the formation of lasting memory traces."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In adult human brain, GRIN3A is expressed at lower levels and assembles with NR1 and NR2 subunits into receptor complexes that may contribute uniquely to synaptic modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition to its role in synapse physiology, genetic studies have implicated GRIN3A in neuropsychiatric and neurobehavioral conditions. Missense and rare variants in GRIN3A are associated with increased susceptibility to disorders such as schizophrenia, sexual dysfunction during selective serotonin reuptake inhibitor treatment, and nicotine dependence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, modulatory influences—such as potentiation by zinc acting at the NR1 subunit of NR1/GluN3A receptors—further refine its distinctive signaling and trafficking properties"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and rare truncating mutations in GRIN3A suggest that its loss-of-function may be partially compensated within the glutamate signaling network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings indicate that GRIN3A plays multifaceted roles both in the developmental regulation of synaptic connectivity and in the modulation of adult neural circuitry, with dysregulation of its function contributing to several neuropsychiatric phenotypes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Osama Mohamad, Mingke Song, Ling Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory roles of the NMDA receptor GluN3A subunit in locomotion, pain perception and cognitive functions in adult mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2012.239251"}], "href": "https://doi.org/10.1113/jphysiol.2012.239251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23006484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23006484"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Adam C Roberts, Javier Díez-García, Ramona M Rodriguiz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of NR3A-containing NMDARs is required for synapse maturation and memory consolidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2009.06.016"}], "href": "https://doi.org/10.1016/j.neuron.2009.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19679074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19679074"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Laura A Kehoe, Camilla Bellone, Mathias De Roo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GluN3A promotes dendritic spine pruning and destabilization during postnatal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5183-13.2014"}], "href": "https://doi.org/10.1523/JNEUROSCI.5183-13.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25009255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25009255"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anna Nilsson, Maria Eriksson, E Chris Muly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of NR3A receptor subunits in human native NMDA receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2007.09.008"}], "href": "https://doi.org/10.1016/j.brainres.2007.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17997397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17997397"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jürgen Gallinat, Thomas Götz, Peter Kalus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations of the NR3A subunit of the NMDA receptor modulate prefrontal cerebral activity in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cogn Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1162/jocn.2007.19.1.59"}], "href": "https://doi.org/10.1162/jocn.2007.19.1.59"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17214563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17214563"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Roy H Perlis, Gonzalo Laje, Jordan W Smoller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2009.4"}], "href": "https://doi.org/10.1038/npp.2009.4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19295509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19295509"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Atsushi Takata, Yoshimi Iwayama, Yasuhisa Fukuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A population-specific uncommon variant in GRIN3A associated with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2012.10.024"}], "href": "https://doi.org/10.1016/j.biopsych.2012.10.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23237318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23237318"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "J Yang, S Wang, Z Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The contribution of rare and common variants in 30 genes to risk nicotine dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2014.156"}], "href": "https://doi.org/10.1038/mp.2014.156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25450229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25450229"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Christian Madry, Heinrich Betz, Jörg R P Geiger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Supralinear potentiation of NR1/NR3A excitatory glycine receptors by Zn2+ and NR1 antagonist."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0805624105"}], "href": "https://doi.org/10.1073/pnas.0805624105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18711142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18711142"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "J Tarabeux, O Kebir, J Gauthier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tp.2011.52"}], "href": "https://doi.org/10.1038/tp.2011.52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22833210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22833210"}]}]}]}