Molecular and genetic determinants of the NMDA receptor for superior learning and memory functions

Stephanie Jacobs, Zhenzhong Cui, Ruiben Feng, Huimin Wang, Deheng Wang, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The opening-duration of the NMDA receptors implements Hebb's synaptic coincidence-detection and is long thought to be the rate-limiting factor underlying superior memory. Here, we investigate the molecular and genetic determinants of the NMDA receptors by testing the "synaptic coincidence-detection time-duration" hypothesis vs. "GluN2B intracellular signaling domain" hypothesis. Accordingly, we generated a series of GluN2A, GluN2B, and GluN2D chimeric subunit transgenic mice in which C-terminal intracellular domains were systematically swapped and overexpressed in the forebrain excitatory neurons. The data presented in the present study supports the second hypothesis, the "GluN2B intracellular signaling domain" hypothesis. Surprisingly, we found that the voltage-gated channel opening-durations through either GluN2A or GluN2B are sufficient and their temporal differences are marginal. In contrast, the C-terminal intracellular domain of the GluN2B subunit is necessary and sufficient for superior performances in long-term novel object recognition and cued fear memories and superior flexibility in fear extinction. Intriguingly, memory enhancement correlates with enhanced longterm potentiation in the 10-100 Hz range while requiring intact long-term depression capacity at the 1-5 Hz range.

Original languageEnglish (US)
Article numbere111865
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 31 2014

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N-Methyl-D-Aspartate Receptors
Molecular Biology
learning
Learning
fearfulness
Data storage equipment
receptors
Fear
duration
Object recognition
Prosencephalon
Transgenic Mice
Neurons
extinction
neurons
genetically modified organisms
Depression
brain
mice
Testing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Molecular and genetic determinants of the NMDA receptor for superior learning and memory functions. / Jacobs, Stephanie; Cui, Zhenzhong; Feng, Ruiben; Wang, Huimin; Wang, Deheng; Tsien, Joseph Zhuo.

In: PloS one, Vol. 9, No. 10, e111865, 31.10.2014.

Research output: Contribution to journalArticle

Jacobs, Stephanie ; Cui, Zhenzhong ; Feng, Ruiben ; Wang, Huimin ; Wang, Deheng ; Tsien, Joseph Zhuo. / Molecular and genetic determinants of the NMDA receptor for superior learning and memory functions. In: PloS one. 2014 ; Vol. 9, No. 10.
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