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Neuron. 2003 Jun 19;38(6):965-76.

Enhanced learning and memory in mice lacking Na+/Ca2+ exchanger 2.

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National Creative Research Initiative Center for Calcium & Learning, Korea Institute of Science and Technology, 136-791, Seoul, South Korea.


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.

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