Impairment of spatial short-term memory following acute administration of the NMDA receptor antagonist in heterozygous rolling Nagoya mice carrying the CaV2.1α1 mutation

Heterozygous rolling Nagoya (rol/+) mice carrying CaV2.1α1 mutation demonstrated normal behavior in Y maze test. Similar spontaneous alternation patterns were noted in wild-type and rol/+ mice injected with N-methyl-d-aspartate (NMDA; 0–50 mg/kg, sc). Systemic injection of NMDA receptor blocker (MK-801; 0.05 mg/kg, ip) or intrahippocampal injection of MK-801 (0.5 μg/side), which had no effect in wild-type controls, decreased spatial cognition in rol/+ mice. These results indicate that CaV2.1α1 mutation probably through decrease in Ca2+ influx lowers the threshold for learning impairment. The combination subthreshold pharmacological and genetic approach is useful to study functional pathways in neuronal circuits.