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

117 Citations (Scopus)

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

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neuronal Plasticity
Tamoxifen
Phosphorylation
Ligands
Calcium-Calmodulin-Dependent Protein Kinases
AMPA Receptors
Spatial Learning
Long-Term Potentiation
Glutamate Receptors
Estrogen Receptors
Synapses
Transgenic Mice
Learning
Neurons
Membranes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhou, Y., Takahashi, E., Li, W., Halt, A., Wiltgen, B., Ehninger, D., ... 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

Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. / Zhou, Yu; Takahashi, Eiki; Li, Weidong; Halt, Amy; Wiltgen, Brian; Ehninger, Dan; Li, Guo Dong; Hell, Johannes W; Kennedy, Mary B.; Silva, Alcino J.

In: Journal of Neuroscience, Vol. 27, No. 50, 12.12.2007, p. 13843-13853.

Research output: Contribution to journalArticle

Zhou, Y, Takahashi, E, Li, W, Halt, A, Wiltgen, B, Ehninger, D, Li, GD, Hell, JW, Kennedy, MB & Silva, AJ 2007, 'Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning', Journal of Neuroscience, vol. 27, no. 50, pp. 13843-13853. https://doi.org/10.1523/JNEUROSCI.4486-07.2007
Zhou, Yu ; Takahashi, Eiki ; Li, Weidong ; Halt, Amy ; Wiltgen, Brian ; Ehninger, Dan ; Li, Guo Dong ; Hell, Johannes W ; Kennedy, Mary B. ; Silva, Alcino J. / Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 50. pp. 13843-13853.
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