Editing NMDA receptor (section)

===GluN2===
[[File:Model of NR2 Subunit of NMDA receptor (vertebrate and invertebrate).jpg|thumb|NR2 subunit in vertebrates (left) and invertebrates (right). Ryan et al., 2008]]
While a single GluN2 subunit is found in [[invertebrate]] [[organism]]s, four distinct isoforms of the GluN2 subunit are expressed in [[vertebrate]]s and are referred to with the nomenclature GluN2A through GluN2D (encoded by [[GRIN2A]], [[GRIN2B]], [[GRIN2C]], [[GRIN2D]]). Strong evidence shows that the genes encoding the GluN2 subunits in vertebrates have undergone at least two rounds of [[gene duplication]].<ref name="pmid20976280">
{{cite journal | vauthors = Teng H, Cai W, Zhou L, Zhang J, Liu Q, Wang Y, Dai W, Zhao M, Sun Z | display-authors = 6 | title = Evolutionary mode and functional divergence of vertebrate NMDA receptor subunit 2 genes | journal = PLOS ONE | volume = 5 | issue = 10 | pages = e13342 | date = October 2010 | pmid = 20976280 | pmc = 2954789 | doi = 10.1371/journal.pone.0013342 | doi-access = free | bibcode = 2010PLoSO...513342T }}</ref> They contain the binding-site for [[glutamate]]. More importantly, each GluN2 subunit has a different intracellular C-terminal domain that can interact with different sets of signaling molecules.<ref name="Ryan2009">{{cite journal | vauthors = Ryan TJ, Grant SG | title = The origin and evolution of synapses | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 10 | pages = 701–712 | date = October 2009 | pmid = 19738623 | doi = 10.1038/nrn2717 | s2cid = 5164419 }}</ref> Unlike GluN1 subunits, GluN2 subunits are expressed differentially across various cell types and developmental timepoints and control the electrophysiological properties of the NMDA receptor. In classic circuits, GluN2B is mainly present in immature neurons and in extrasynaptic locations such as [[growth cone]]s,<ref name="Georgiev2008">{{cite journal | vauthors = Georgiev D, Taniura H, Kambe Y, Takarada T, Yoneda Y | title = A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 neuronal differentiation | journal = Experimental Cell Research | volume = 314 | issue = 14 | pages = 2603–2617 | date = August 2008 | pmid = 18586028 | doi = 10.1016/j.yexcr.2008.06.009 }}</ref> and contains the binding-site for the selective inhibitor [[ifenprodil]].<ref name="Bunk2014">{{cite journal | vauthors = Bunk EC, König HG, Prehn JH, Kirby BP | title = Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus | journal = Journal of Neuroscience Research | volume = 92 | issue = 6 | pages = 679–691 | date = June 2014 | pmid = 24464409 | doi = 10.1002/jnr.23347 | s2cid = 18582691 | url = https://figshare.com/articles/journal_contribution/10798256 }}</ref> However, in [[pyramidal cell]] [[synapse]]s in the newly evolved primate [[dorsolateral prefrontal cortex]], GluN2B are exclusively within the [[postsynaptic density]], and mediate higher cognitive operations such as [[working memory]].<ref name="Wang2013">{{cite journal | vauthors = Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang XJ, Arnsten AF | display-authors = 6 | title = NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex | journal = Neuron | volume = 77 | issue = 4 | pages = 736–749 | date = February 2013 | pmid = 23439125 | pmc = 3584418 | doi = 10.1016/j.neuron.2012.12.032 }}</ref> This is consistent with the expansion in GluN2B actions and expression across the cortical hierarchy in [[monkey]]s <ref name="Yang2018">{{cite journal | vauthors = Yang ST, Wang M, Paspalas CD, Crimins JL, Altman MT, Mazer JA, Arnsten AF | title = Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex | journal = Cerebral Cortex | volume = 28 | issue = 4 | pages = 1458–1471 | date = April 2018 | pmid = 29351585 | pmc = 6041807 | doi = 10.1093/cercor/bhx357 }}</ref> and [[human]]s <ref name="Burt2018">{{cite journal | vauthors = Burt JB, Demirtaş M, Eckner WJ, Navejar NM, Ji JL, Martin WJ, Bernacchia A, Anticevic A, Murray JD | display-authors = 6 | title = Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography | journal = Nature Neuroscience | volume = 21 | issue = 9 | pages = 1251–1259 | date = September 2018 | pmid = 30082915 | pmc = 6119093 | doi = 10.1038/s41593-018-0195-0 }}</ref> and across [[primate]] [[cerebral cortex|cortex]] [[evolution]].<ref name="Muntane2015">{{cite journal | vauthors = Muntané G, Horvath JE, Hof PR, Ely JJ, Hopkins WD, Raghanti MA, Lewandowski AH, Wray GA, Sherwood CC | display-authors = 6 | title = Analysis of synaptic gene expression in the neocortex of primates reveals evolutionary changes in glutamatergic neurotransmission | journal = Cerebral Cortex | volume = 25 | issue = 6 | pages = 1596–1607 | date = June 2015 | pmid = 24408959 | pmc = 4428301 | doi = 10.1093/cercor/bht354 }}</ref>