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

Neuron. 2003 Jun 19;38(6):965-76. doi: 10.1016/s0896-6273(03)00334-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Chemistry
  • Calcium / metabolism
  • Cell Membrane / physiology
  • Conditioning, Psychological / physiology
  • Electric Conductivity
  • Fear
  • Gene Expression
  • Learning / physiology*
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Mutation
  • Neuronal Plasticity
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / physiology*
  • Synaptic Transmission


  • Protein Isoforms
  • Slc8a2 protein, mouse
  • Sodium-Calcium Exchanger
  • Calcium