Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory.
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.
Zeng
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H
Howard Hughes Medical Institute, RIKEN-MIT Neuroscience Research Center, Center for Learning & Memory, Departments of Biology and Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Chattarji
S
S
Barbarosie
M
M
Rondi-Reig
L
L
Philpot
B D
BD
Miyakawa
T
T
Bear
M F
MF
Tonegawa
S
S
D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018390:Gene Targeting; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D020033:Protein Isoforms; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin