Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory

Cell. 2001 Nov 30;107(5):617-29. doi: 10.1016/s0092-8674(01)00585-2.


Calcineurin is a calcium-dependent protein phosphatase that has been implicated in various aspects of synaptic plasticity. By using conditional gene-targeting techniques, we created mice in which calcineurin activity is disrupted specifically in the adult forebrain. At hippocampal Schaffer collateral-CA1 synapses, LTD was significantly diminished, and there was a significant shift in the LTD/LTP modification threshold in mutant mice. Strikingly, although performance was normal in hippocampus-dependent reference memory tasks, including contextual fear conditioning and the Morris water maze, the mutant mice were impaired in hippocampus-dependent working and episodic-like memory tasks, including the delayed matching-to-place task and the radial maze task. Our results define a critical role for calcineurin in bidirectional synaptic plasticity and suggest a novel mechanistic distinction between working/episodic-like memory and reference memory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcineurin / genetics
  • Calcineurin / metabolism*
  • Conditioning, Psychological / physiology
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Targeting
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • In Situ Hybridization
  • In Vitro Techniques
  • Learning / physiology*
  • Male
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques
  • Protein Isoforms
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Protein Isoforms
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate
  • Calcineurin