Impairment of spatial short-term memory following acute administration of the NMDA receptor antagonist in heterozygous rolling Nagoya mice carrying the Ca V 2.1 alpha1 mutation.
Heterozygous rolling Nagoya (rol/+) mice carrying Ca(V)2.1 alpha(1) 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; 0-50mg/kg, sc). Systemic injection of NMDA receptor blocker (MK-801; 0.05 mg/kg, ip) or intrahippocampal injection of MK-801 (0.5 microg/side), which had no effect in wild-type controls, decreased spatial cognition in rol/+ mice. These results indicate that Ca(V)2.1 alpha(1) mutation probably through decrease in Ca(2+) influx lowers the threshold for learning impairment. The combination subthreshold pharmacological and genetic approach is useful to study functional pathways in neuronal circuits.
Takahashi
Eiki
E
RIKEN Brain Science Institute, Research Resources Center, Hirosawa 2-1, Wako, Saitama 351-0198, Japan. etakahashi@brain.riken.jp
Niimi
Kimie
K
Itakura
Chitoshi
C
D000818:Animals; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000235:genetics / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006579:Heterozygote; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D016202:N-Methylaspartate / Q000378:metabolism; D009483:Neuropsychological Tests; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate