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

Hongkui Zeng, Sumantra Chattarji, Michaela Barbarosie, Laure Rondi-Reig, Benjamin D. Philpot, Tsuyoshi Miyakawa, Mark F. Bear, Susumu Tonegawa

Research output: Contribution to journalArticle

372 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)617-629
Number of pages13
JournalCell
Volume107
Issue number5
DOIs
Publication statusPublished - 30-11-2001
Externally publishedYes

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Neuronal Plasticity
Episodic Memory
Calcineurin
Prosencephalon
Plasticity
Hippocampus
Data storage equipment
Gene Targeting
Phosphoprotein Phosphatases
Synapses
Fear
Calcium
Water
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zeng, Hongkui ; Chattarji, Sumantra ; Barbarosie, Michaela ; Rondi-Reig, Laure ; Philpot, Benjamin D. ; Miyakawa, Tsuyoshi ; Bear, Mark F. ; Tonegawa, Susumu. / Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. In: Cell. 2001 ; Vol. 107, No. 5. pp. 617-629.
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Zeng, H, Chattarji, S, Barbarosie, M, Rondi-Reig, L, Philpot, BD, Miyakawa, T, Bear, MF & Tonegawa, S 2001, 'Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory', Cell, vol. 107, no. 5, pp. 617-629. https://doi.org/10.1016/S0092-8674(01)00585-2

Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. / Zeng, Hongkui; Chattarji, Sumantra; Barbarosie, Michaela; Rondi-Reig, Laure; Philpot, Benjamin D.; Miyakawa, Tsuyoshi; Bear, Mark F.; Tonegawa, Susumu.

In: Cell, Vol. 107, No. 5, 30.11.2001, p. 617-629.

Research output: Contribution to journalArticle

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AU - Philpot, Benjamin D.

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AU - Bear, Mark F.

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