Differential effects of enrichment on learning and memory function in NR2B transgenic mice

Y. P. Tang, H. Wang, R. Feng, M. Kyin, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

It has been known that environmental enrichment leads to better learning and memory in mice. However, the molecular mechanisms are not known. In this study, we used the 10th-12th of the NR2B transgenic (Tg) lines, in which the NMDA receptor function is enhanced via the NR2B subunit transgene in neurons of the forebrain, to test the hypothesis of the involvement of NMDA receptor function in enrichment-induced better learning and memory. Consistent with our previous results, both larger long-term potentiation (LTP) in the hippocampus and superior learning and memory were observed in naive NR2B Tg mice even after the 10th-12th generation of breeding. After enrichment, wild-type mice exhibited overall improvement in their performances in contextual and cued conditioning, fear extinctions, and novel object recognition tasks. Interestingly, the same enrichment procedures could not further increase the performance of NR2B Tg mice in contextual conditioning, cued conditioning, or fear extinction, thereby indicating that enhanced NMDA receptor function can occlude these enrichment effects. However, we found that in the novel object recognition task enriched NR2B Tg mice exhibited much longer recognition memory (up to 1 week), compared to that (up to 3 days) in naive NR2B Tg mice. Furthermore, our biochemical experiments showed that enrichment significantly increased protein levels of GluR1, NR2B, and NR2A subunits of glutamate receptors in both wild-type and NR2B Tg mice. Therefore, our results suggest an interactive nature of molecular pathways involved in both environmental and genetic NMDA receptor manipulations for enhancing learning and memory.

Original languageEnglish (US)
Pages (from-to)779-790
Number of pages12
JournalNeuropharmacology
Volume41
Issue number6
DOIs
StatePublished - Oct 25 2001
Externally publishedYes

Fingerprint

Transgenic Mice
N-Methyl-D-Aspartate Receptors
Learning
Fear
Long-Term Potentiation
Glutamate Receptors
Prosencephalon
Transgenes
Breeding
Hippocampus
Neurons
Conditioning (Psychology)
Recognition (Psychology)
Proteins
Psychological Extinction

Keywords

  • Enrichment
  • Fear conditioning
  • Fear extinction
  • GluR1
  • LTP
  • Learning and memory
  • NMDA receptor
  • NR2A
  • NR2B
  • Novel object recognition

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Differential effects of enrichment on learning and memory function in NR2B transgenic mice. / Tang, Y. P.; Wang, H.; Feng, R.; Kyin, M.; Tsien, Joseph Zhuo.

In: Neuropharmacology, Vol. 41, No. 6, 25.10.2001, p. 779-790.

Research output: Contribution to journalArticle

Tang, Y. P. ; Wang, H. ; Feng, R. ; Kyin, M. ; Tsien, Joseph Zhuo. / Differential effects of enrichment on learning and memory function in NR2B transgenic mice. In: Neuropharmacology. 2001 ; Vol. 41, No. 6. pp. 779-790.
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