Maintenance of superior learning and memory function in NR2B transgenic mice during ageing

Eur J Neurosci. 2007 Mar;25(6):1815-22. doi: 10.1111/j.1460-9568.2007.05431.x.

Abstract

Brain ageing represents a general and evolutionarily conserved phenomenon and is marked by gradual declines in cognitive functions such as learning and memory. As a synaptic coincidence detector, the N-methyl-d-aspartate (NMDA) receptor is known to be essential for the induction of synaptic plasticity and memory formation. Here, we test the hypothesis that up-regulation of NR2B expression is beneficial for learning and memory in the aged animals. Our in vitro recordings show that the aged transgenic mice with the forebrain-specific overexpression of the NR2B subunit indeed exhibit more robust hippocampal long-term potentiation (LTP) induced by either high-frequency stimulation or theta-stimulation protocol. Furthermore, those aged NR2B transgenic mice consistently outperform their wild-type littermates in five different learning and memory tests, namely, novel object recognition, contextual and cued fear conditioning, spatial reference memory, and spatial working memory T-maze task. Thus, we conclude that increased expression of NR2B in the forebrain improves learning and memory function in the aged brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Behavior, Animal
  • Conditioning, Psychological / physiology*
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Exploratory Behavior / physiology
  • Fear
  • Hippocampus / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / genetics*
  • Long-Term Potentiation / radiation effects
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Transgenic
  • Neuropsychological Tests / statistics & numerical data
  • Prosencephalon / physiology
  • Reaction Time / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Up-Regulation / physiology

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate