PMID- 11733061
DA - 20011204
DCOM- 20011228
IS - 0092-8674
VI - 107
IP - 5
DP - 2001 Nov 30
TI - Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory.
PG - 617-29 AB - 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.
AD - 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.
FAU - Zeng, H
AU - Zeng H
FAU - Chattarji, S
AU - Chattarji S
FAU - Barbarosie, M
AU - Barbarosie M
FAU - Rondi-Reig, L
AU - Rondi-Reig L
FAU - Philpot, B D
AU - Philpot BD
FAU - Miyakawa, T
AU - Miyakawa T
FAU - Bear, M F
AU - Bear MF
FAU - Tonegawa, S
AU - Tonegawa S
LA - eng
ID - MH58880-03/MH/NIMH
PT - Journal Article
CY - United States
TA - Cell
JID - 0413066
RN - 0 (Protein Isoforms)
RN - 0 (Protein Subunits)
RN - 0 (Receptors, N-Methyl-D-Aspartate)
RN - EC 3.1.3.- (Calcineurin)
SB - IM
MH - Animal
MH - Calcineurin/genetics/*metabolism
MH - Conditioning (Psychology)/physiology
MH - Excitatory Postsynaptic Potentials/physiology
MH - Gene Targeting
MH - Hippocampus/cytology/*physiology
MH - In Situ Hybridization
MH - In Vitro
MH - Learning/*physiology
MH - Male
MH - Maze Learning/physiology
MH - Memory/*physiology
MH - Mice
MH - Mice, Inbred C57BL
MH - Mice, Knockout
MH - Neuronal Plasticity/*physiology
MH - Patch-Clamp Techniques
MH - Protein Isoforms
MH - Protein Subunits
MH - Receptors, N-Methyl-D-Aspartate/metabolism
MH - Support, Non-U.S. Gov't
MH - Support, U.S. Gov't, P.H.S.
EDAT- 2001/12/06 10:00
MHDA- 2002/01/05 10:01
AID - S0092867401005852 [pii]
PST - ppublish
SO - Cell 2001 Nov 30;107(5):617-29.