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

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.