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Science 20 August 1993:
Vol. 261. no. 5124, pp. 1051 - 1055
DOI: 10.1126/science.8394601
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Articles

Science, Vol 261, Issue 5124, 1051-1055
Copyright © 1993 by American Association for the Advancement of Science

articles

An essential role for protein phosphatases in hippocampal long-term depression

RM Mulkey, CE Herron, and RC Malenka

Department of Psychiatry, University of California, San Francisco 94143-0984.

The effectiveness of long-term potentiation (LTP) as a mechanism for information storage would be severely limited if processes that decrease synaptic strength did not also exist. In area CA1 of the rat hippocampus, prolonged periods of low-frequency afferent stimulation elicit a long-term depression (LTD) that is specific to the stimulated input. The induction of LTD was blocked by the extracellular application of okadaic acid or calyculin A, two inhibitors of protein phosphatases 1 and 2A. The loading of CA1 cells with microcystin LR, a membrane-impermeable protein phosphatase inhibitor, or calmodulin antagonists also blocked or attenuated LTD. The application of calyculin A after the induction of LTD reversed the synaptic depression, suggesting that phosphatase activity is required for the maintenance of LTD. These findings indicate that the synaptic activation of protein phosphatases plays an important role in the regulation of synaptic transmission.


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   Abstract »    Full Text »    PDF »
Postsynaptic Calcineurin Activity Downregulates Synaptic Transmission by Weakening Intracellular Ca2+ Signaling Mechanisms in Hippocampal CA1 Neurons.
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Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region.
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Nitric Oxide Facilitates Long-Term Potentiation, But Not Long-Term Depression.
P. L. Malen and P. F. Chapman (1997)
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A synaptic basis for memory storage in the cerebral cortex.
M. F. Bear (1996)
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Induction of Hippocampal Long-Term Depression Requires Release of Ca2+ from Separate Presynaptic and Postsynaptic Intracellular Stores.
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J. Neurosci. 16, 5951-5960
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Bidirectional Regulation of Protein Kinase Mzeta in the Maintenance of Long-Term Potentiation and Long-Term Depression.
S. Hrabetova and T. C. Sacktor (1996)
J. Neurosci. 16, 5324-5333
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Long-Term Potentiation in Distinct Subtypes of Hippocampal Nonpyramidal Neurons.
G. Maccaferri and C. J. McBain (1996)
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Increased Susceptibility to Induction of Long-Term Depression and Long-Term Potentiation Reversal during Aging.
C. M. Norris, D. L. Korol, and T. C. Foster (1996)
J. Neurosci. 16, 5382-5392
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Proactive and retrograde effects on LTP produced by theta pulse stimulation: mechanisms and characteristics of LTP reversal in vitro..
U Staubli and D Chun (1996)
Learn. Mem. 3, 96-105
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Long-term potentiation induces synaptic plasticity at nontetanized adjacent synapses..
C M Coussens and T J Teyler (1996)
Learn. Mem. 3, 106-114
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The balance between postsynaptic Ca(2+)-dependent protein kinase and phosphatase activities controlling synaptic strength..
J H Wang and P T Kelly (1996)
Learn. Mem. 3, 170-181
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Calcium Regulation of Calcineurin Phosphatase Activity by Its B Subunit and Calmodulin.
B. A. Perrino, L. Y. Ng, and T. R. Soderling (1995)
J. Biol. Chem. 270, 340-346
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Identification in the Calcineurin A Subunit of the Domain That Binds the Regulatory B Subunit.
Y. Watanabe, B. A. Perrino, B. H. Chang, and T. R. Soderling (1995)
J. Biol. Chem. 270, 456-460
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REVIEW {blacksquare} : LTP and LTD: Dynamic and Interactive Processes of Synaptic Plasticity.
R. C. Malenka (1995)
Neuroscientist 1, 35-42
   Abstract »    PDF »
Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases..
T J O'Dell and E R Kandel (1994)
Learn. Mem. 1, 129-139
   Abstract »    PDF »
Long Term Depression in the CA1 Field Is Associated with a Transient Decrease in Pre- and Postsynaptic PKC Substrate Phosphorylation.
G. M. J. Ramakers, K. Heinen, W.-H. Gispen, and P. N. E. de Graan (2000)
J. Biol. Chem. 275, 28682-28687
   Abstract »    Full Text »    PDF »
gamma -Aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses.
T.-p. Yu, S. McKinney, H. A. Lester, and N. Davidson (2001)
PNAS 98, 5264-5269
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)