Enhanced learning and memory in mice lacking Na+/Ca2+ exchanger 2.
The plasma membrane Na(+)/Ca(2+) exchanger (NCX) plays a role in regulation of intracellular Ca(2+) concentration via the forward mode (Ca(2+) efflux) or the reverse mode (Ca(2+) influx). To define the physiological function of the exchanger in vivo, we generated mice deficient for NCX2, the major isoform in the brain. Mutant hippocampal neurons exhibited a significantly delayed clearance of elevated Ca(2+) following depolarization. The frequency threshold for LTP and LTD in the hippocampal CA1 region was shifted to a lowered frequency in the mutant mice, thereby favoring LTP. Behaviorally, the mutant mice exhibited enhanced performance in several hippocampus-dependent learning and memory tasks. These results demonstrate that NCX2 can be a temporal regulator of Ca(2+) homeostasis and as such is essential for the control of synaptic plasticity and cognition.
Jeon
Daejong
D
National Creative Research Initiative Center for Calcium & Learning, Korea Institute of Science and Technology, 136-791, Seoul, South Korea.
Yang
Yu-Mi
YM
Jeong
Myung-Jin
MJ
Philipson
Kenneth D
KD
Rhim
Hyewhon
H
Shin
Hee-Sup
HS
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D004553:Electric Conductivity; D005239:Fear; D015870:Gene Expression; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009473:Neuronal Plasticity; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission
D020033:Protein Isoforms; C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; D002118:Calcium