Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory.
To investigate the roles phosphatases play in hippocampal-dependent memory, we studied transgenic mice overexpressing a truncated form of calcineurin. These mice have normal short-term memory but defective long-term memory evident on both a spatial task and on a visual recognition task, providing genetic evidence for the role of the rodent hippocampus in spatial and nonspatial memory. The defect in long-term memory could be fully rescued by increasing the number of training trials, suggesting that the mice have the capacity for long-term memory. We next analyzed mice overexpressing calcineurin in a regulated manner and found the memory defect is reversible and not due to a developmental abnormality. Our behavioral results suggest that calcineurin has a role in the transition from short- to long-term memory, which correlates with a novel intermediate phase of LTP.
Mansuy
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IM
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York 10032, USA.
Mayford
M
M
Jacob
B
B
Kandel
E R
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Bach
M E
ME
D000818:Animals; D019703:Calcineurin / Q000235:genetics* / Q000502:physiology; D004318:Doxycycline / Q000494:pharmacology; D004558:Electric Stimulation; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics; D013037:Spatial Behavior / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019076:Transgenes / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D011994:Recombinant Proteins; D015534:Trans-Activators; D019703:Calcineurin; D013752:Tetracycline; D004318:Doxycycline