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Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior

Research output: Contribution to journalArticle

  • Tomas J. Ryan
  • Maksym V. Kopanitsa
  • Tim Indersmitten
  • Jess Nithianantharajah
  • Nurudeen O. Afinowi
  • Charles Pettit
  • Lianne E. Stanford
  • Rolf Sprengel
  • Lisa M. Saksida
  • Timothy J. Bussey
  • Thomas J. O'Dell
  • Seth G. N. Grant
  • Noboru Komiyama

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    Rights statement: Published in final edited form as: Nat Neurosci. Jan 2013; 16(1): 25–32.

    Accepted author manuscript, 1.75 MB, PDF document

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalNature Neuroscience
Issue number1
Early online date2 Dec 2012
Publication statusPublished - 2013


Two genome duplications early in the vertebrate lineage expanded gene families, including GluN2 subunits of the NMDA receptor. Diversification between the four mammalian GluN2 proteins occurred primarily at their intracellular C-terminal domains (CTDs). To identify shared ancestral functions and diversified subunit-specific functions, we exchanged the exons encoding the GluN2A (also known as Grin2a) and GluN2B (also known as Grin2b) CTDs in two knock-in mice and analyzed the mice's biochemistry, synaptic physiology, and multiple learned and innate behaviors. The eight behaviors were genetically separated into four groups, including one group comprising three types of learning linked to conserved GluN2A/B regions. In contrast, the remaining five behaviors exhibited subunit-specific regulation. GluN2A/B CTD diversification conferred differential binding to cytoplasmic MAGUK proteins and differential forms of long-term potentiation. These data indicate that vertebrate behavior and synaptic signaling acquired increased complexity from the duplication and diversification of ancestral GluN2 genes.

    Research areas

  • Receptors, Behaviour, Learning, Synaptic transmission

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