Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning

Yu Zhou, Eiki Takahashi, Weidong Li, Amy Halt, Brian Wiltgen, Dan Ehninger, Guo Dong Li, Johannes W Hell, Mary B. Kennedy, Alcino J. Silva

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBDG521R. Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBDG521R-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of αCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning.

Original languageEnglish (US)
Pages (from-to)13843-13853
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number50
DOIs
StatePublished - Dec 12 2007
Externally publishedYes

Keywords

  • CaMKII
  • Learning
  • Memory
  • NMDA receptor
  • Plasticity
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning'. Together they form a unique fingerprint.

  • Cite this

    Zhou, Y., Takahashi, E., Li, W., Halt, A., Wiltgen, B., Ehninger, D., Li, G. D., Hell, J. W., Kennedy, M. B., & Silva, A. J. (2007). Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. Journal of Neuroscience, 27(50), 13843-13853. https://doi.org/10.1523/JNEUROSCI.4486-07.2007