Increased thresholds for long-term potentiation and contextual learning in mice lacking the NMDA-type glutamate...

The NMDA-type glutamate receptor (GluR) channel, composed of the GluRepsilon and GluRzeta subunits, plays a key role in synaptic plasticity in the CNS. The mutant mice lacking the GluRepsilon1 subunit exhibited a reduction in hippocampal long-term potentiation (LTP), but a stronger tetanic stimulation restored the impairment and the saturation level of LTP was unaltered. These results suggest an increase of threshold for LTP induction in the GluRepsilon1 mutant mice. After a series of backcrosses we established a GluRepsilon1 mutant mouse line with a 99.99% pure C57BL/6 genetic background. The performance of the mutant mice in tone- and context-dependent fear conditioning tests was comparable with that of the wild-type mice. However, a significant difference in the extent of contextual learning became apparent when the chamber exposure time before footshock was shortened. Furthermore, there was a significant difference in freezing responses immediately after footshock on the conditioning day between the wild-type and mutant mice, and the difference was not restored by longer chamber exposure in contrast to the contextual learning on the next day of the conditioning. These results suggest that the GluRepsilon1 subunit of the NMDA receptor channel is a determinant of thresholds for both hippocampal LTP and contextual learning and plays differential roles in two forms of contextual fear memories.