{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:51:15Z","timestamp":1787849475662,"version":"build-2784847793"},"reference-count":78,"publisher":"Cold Spring Harbor Laboratory","issue":"6","funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["ONR#000141010198"],"award-info":[{"award-number":["ONR#000141010198"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R15AG045820-01A1"],"award-info":[{"award-number":["1R15AG045820-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Learn. Mem."],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p><jats:italic>N<\/jats:italic>-methyl-<jats:sc>d<\/jats:sc>-aspartate receptors (NMDARs) at excitatory synapses are central to activity-dependent synaptic plasticity and learning and memory. NMDARs act as ionotropic and metabotropic receptors by elevating postsynaptic calcium concentrations and by direct intracellular protein signaling. In the forebrain, these properties are controlled largely by the auxiliary GluN2 subunits, GluN2A and GluN2B. While calcium conductance through NMDAR channels and intracellular protein signaling make separate contributions to synaptic plasticity, it is not known if these properties individually influence learning and memory. To address this issue, we created chimeric GluN2 subunits containing the amino-terminal domain and transmembrane domains from GluN2A or GluN2B fused to the carboxy-terminal domain of GluN2B (termed ABc) or GluN2A ATD (termed BAc), respectively, and expressed these mutated GluN2 subunits in transgenic mice. Expression was confirmed at the mRNA level and protein subunit translation and translocation into dendrites were observed in forebrain neurons. In the spatial version of the Morris water maze, BAc mice displayed signs of a learning deficit. In contrast, ABc animals performed similarly to wild-types during training, but showed a more direct approach to the goal location during a long-term memory test. There was no effect of ABc or BAc expression in a nonspatial water escape task. Since background expression is predominantly GluN2A in mature animals, the results suggest that spatial learning is more sensitive to manipulations of the amino-terminal domain and transmembrane domains (calcium conductance) and long-term memory is regulated more by the carboxy-terminal domain (intracellular protein signaling).<\/jats:p>","DOI":"10.1101\/lm.047290.118","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T13:46:26Z","timestamp":1526391986000},"page":"264-272","source":"Crossref","is-referenced-by-count":11,"title":["Separate functional properties of NMDARs regulate distinct aspects of spatial cognition"],"prefix":"10.1101","volume":"25","author":[{"given":"Erin M.","family":"Sanders","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akua O.","family":"Nyarko-Odoom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Hong","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Keith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Pyon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Kozma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohima","family":"Sanyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"McHail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1616-8011","authenticated-orcid":false,"given":"Theodore C.","family":"Dumas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2021111207512562000_25.6.264.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2155-07.2007"},{"key":"2021111207512562000_25.6.264.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6773(73)80144-0"},{"key":"2021111207512562000_25.6.264.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3639-07.2008"},{"key":"2021111207512562000_25.6.264.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00776-6"},{"key":"2021111207512562000_25.6.264.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.034"},{"key":"2021111207512562000_25.6.264.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608492103"},{"key":"2021111207512562000_25.6.264.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.035"},{"key":"2021111207512562000_25.6.264.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.07.016"},{"key":"2021111207512562000_25.6.264.9","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21336"},{"key":"2021111207512562000_25.6.264.10","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.160"},{"key":"2021111207512562000_25.6.264.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0640-10.2010"},{"key":"2021111207512562000_25.6.264.12","first-page":"242","article-title":"GluN1 and GluN2A NMDA receptor subunits increase in the hippocampus during memory consolidation in the rat","volume":"10","year":"2017","journal-title":"Front Behav Neurosci"},{"key":"2021111207512562000_25.6.264.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.07.003"},{"key":"2021111207512562000_25.6.264.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-16-06844.1999"},{"key":"2021111207512562000_25.6.264.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(02)00270-X"},{"key":"2021111207512562000_25.6.264.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00215-4"},{"key":"2021111207512562000_25.6.264.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1825-17.2017"},{"key":"2021111207512562000_25.6.264.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.08.002"},{"key":"2021111207512562000_25.6.264.19","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20077"},{"key":"2021111207512562000_25.6.264.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811025106"},{"key":"2021111207512562000_25.6.264.21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.080028"},{"key":"2021111207512562000_25.6.264.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4022-09.2010"},{"key":"2021111207512562000_25.6.264.23","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20230"},{"key":"2021111207512562000_25.6.264.24","first-page":"540","article-title":"Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris Water Maze","volume":"129","year":"1993","journal-title":"Behav Neurosci"},{"key":"2021111207512562000_25.6.264.25","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00457.2010"},{"key":"2021111207512562000_25.6.264.26","doi-asserted-by":"publisher","DOI":"10.1038\/nature07993"},{"key":"2021111207512562000_25.6.264.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.013"},{"key":"2021111207512562000_25.6.264.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.017"},{"key":"2021111207512562000_25.6.264.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1258-06.2006"},{"key":"2021111207512562000_25.6.264.30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111865"},{"key":"2021111207512562000_25.6.264.31","doi-asserted-by":"publisher","DOI":"10.1101\/lm.038521.115"},{"key":"2021111207512562000_25.6.264.32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neubiorev.2016.05.016","article-title":"The water maze paradigm in experimental studies of chronic cognitive disorders: Theory, protocols, analysis, and inference","volume":"68","year":"2016","journal-title":"Neurosci Biobehav Rev"},{"key":"2021111207512562000_25.6.264.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-17-06704.1998"},{"key":"2021111207512562000_25.6.264.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-34-10791.2003"},{"key":"2021111207512562000_25.6.264.35","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2153"},{"key":"2021111207512562000_25.6.264.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3990-05.2006"},{"key":"2021111207512562000_25.6.264.37","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00102"},{"key":"2021111207512562000_25.6.264.38","doi-asserted-by":"publisher","DOI":"10.1038\/nrn753"},{"key":"2021111207512562000_25.6.264.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096615"},{"key":"2021111207512562000_25.6.264.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.012"},{"key":"2021111207512562000_25.6.264.41","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1697-04.2004"},{"key":"2021111207512562000_25.6.264.42","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90009-8"},{"key":"2021111207512562000_25.6.264.43","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1678"},{"key":"2021111207512562000_25.6.264.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.10.003"},{"key":"2021111207512562000_25.6.264.45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neulet.2012.11.019","article-title":"Ligand binding of PDZ domains has various roles in the synaptic clustering of SAP102 and PSD-95","volume":"533","year":"2013","journal-title":"Neurosci Lett"},{"key":"2021111207512562000_25.6.264.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.256.5060.1217"},{"key":"2021111207512562000_25.6.264.47","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90210-0"},{"key":"2021111207512562000_25.6.264.48","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/ncomms1085","article-title":"A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors","volume":"1","year":"2010","journal-title":"Nat Commun"},{"key":"2021111207512562000_25.6.264.49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219454110"},{"key":"2021111207512562000_25.6.264.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2009.02.004"},{"key":"2021111207512562000_25.6.264.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.11.010"},{"key":"2021111207512562000_25.6.264.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.08.011"},{"key":"2021111207512562000_25.6.264.53","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.110.6.1415"},{"key":"2021111207512562000_25.6.264.54","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000078"},{"key":"2021111207512562000_25.6.264.55","doi-asserted-by":"crossref","unstructured":"Petralia RS , Al-Hallaq RA , Wenthold RJ . 2009. Trafficking and Targeting of NMDA Receptors. In Biology of the NMDA receptor. Chapter 8. (ed. Van Dongen AM ). CRC Press\/Taylor & Francis, Boca Raton, FL.","DOI":"10.1201\/9781420044157.ch8"},{"key":"2021111207512562000_25.6.264.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0133-10.2010"},{"key":"2021111207512562000_25.6.264.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.016"},{"key":"2021111207512562000_25.6.264.58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.182600"},{"key":"2021111207512562000_25.6.264.59","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.101.1.62"},{"key":"2021111207512562000_25.6.264.60","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nn.3277","article-title":"Evolution of GluN2A\/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior","volume":"16","year":"2013","journal-title":"Nat Neurosci"},{"key":"2021111207512562000_25.6.264.61","doi-asserted-by":"publisher","DOI":"10.1038\/373151a0"},{"key":"2021111207512562000_25.6.264.62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.335"},{"key":"2021111207512562000_25.6.264.63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/BBLv224n1p1","article-title":"Developmental modification of synaptic NMDAR composition and maturation of glutamatergic synapses: matching postsynaptic slots with receptor pegs","volume":"224","year":"2013","journal-title":"Biol Bull"},{"key":"2021111207512562000_25.6.264.64","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-6-10"},{"key":"2021111207512562000_25.6.264.65","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-03-01260.2000"},{"key":"2021111207512562000_25.6.264.66","doi-asserted-by":"publisher","DOI":"10.1038\/ncb990"},{"issue":"Pt 7","key":"2021111207512562000_25.6.264.67","first-page":"1251","article-title":"The postsynaptic NMDA-receptor--PSD-95 signaling complex in excitatory synapses of the brain","volume":"114","year":"2001","journal-title":"J Cell Sci"},{"key":"2021111207512562000_25.6.264.68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nlm.2017.11.001","article-title":"Post-acquisition hippocampal blockade of the NMDA receptor subunit GluN2A but not GluN2B sustains spatial reference memory retention","volume":"147","year":"2018","journal-title":"Neurobiol Learn Mem"},{"key":"2021111207512562000_25.6.264.69","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80921-6"},{"issue":"Pt A","key":"2021111207512562000_25.6.264.70","first-page":"41","article-title":"Nampt is required for long-term depression and the function of GluN2B subunit-containing NMDA receptors","volume":"119","year":"2015","journal-title":"Brain Res Bull"},{"key":"2021111207512562000_25.6.264.71","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1086\/BBLv219n2p81","article-title":"Rules of engagement: factors that regulate activity-dependent synaptic plasticity during neural network development","volume":"219","year":"2010","journal-title":"Biol Bull"},{"key":"2021111207512562000_25.6.264.72","doi-asserted-by":"publisher","DOI":"10.1038\/43432"},{"key":"2021111207512562000_25.6.264.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.08.005"},{"key":"2021111207512562000_25.6.264.74","doi-asserted-by":"publisher","DOI":"10.1038\/88404"},{"key":"2021111207512562000_25.6.264.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.09.039"},{"key":"2021111207512562000_25.6.264.76","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilu013"},{"key":"2021111207512562000_25.6.264.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.023"},{"key":"2021111207512562000_25.6.264.78","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1365-09.2009"}],"container-title":["Learning &amp; Memory"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/lm.047290.118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T15:52:28Z","timestamp":1636732348000},"score":1,"resource":{"primary":{"URL":"http:\/\/learnmem.cshlp.org\/lookup\/doi\/10.1101\/lm.047290.118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,15]]},"references-count":78,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,5,15]]},"published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1101\/lm.047290.118"],"URL":"https:\/\/doi.org\/10.1101\/lm.047290.118","relation":{},"ISSN":["1549-5485"],"issn-type":[{"value":"1549-5485","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,15]]}}}