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Science 7 October 1988:
Vol. 242. no. 4875, pp. 81 - 84
DOI: 10.1126/science.2845577
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Articles

Science, Vol 242, Issue 4875, 81-84
Copyright © 1988 by American Association for the Advancement of Science

articles

Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission

RC Malenka, JA Kauer, RS Zucker, and RA Nicoll

Department of Pharmacology, School of Medicine, University of California, San Francisco 94143.

Brief repetitive activation of excitatory synapses in the hippocampus leads to an increase in synaptic strength that lasts for many hours. This long-term potentiation (LTP) of synaptic transmission is the most compelling cellular model in the vertebrate brain for learning and memory. The critical role of postsynaptic calcium in triggering LTP has been directly examined using three types of experiment. First, nitr-5, a photolabile nitrobenzhydrol tetracarboxylate calcium chelator, which releases calcium in response to ultraviolet light, was used. Photolysis of nitr-5 injected into hippocampal CA1 pyramidal cells resulted in a large enhancement of synaptic transmission. Second, in agreement with previous results, buffering intracellular calcium at low concentrations blocked LTP. Third, depolarization of the postsynaptic membrane so that calcium entry is suppressed prevented LTP. Taken together, these results demonstrate that an increase in postsynaptic calcium is necessary to induce LTP and sufficient to potentiate synaptic transmission.


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   Abstract »    PDF »
Hebbian depression of isolated neuromuscular synapses in vitro.
Y Dan and M. Poo (1992)
Science 256, 1570-1573
   Abstract »    PDF »
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C Koch, A Zador, and T. Brown (1992)
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   PDF »
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Science 255, 730-733
   Abstract »    PDF »
High probability opening of NMDA receptor channels by L-glutamate.
C. Jahr (1992)
Science 255, 470-472
   Abstract »    PDF »
A requirement for the intercellular messenger nitric oxide in long-term potentiation.
E. Schuman and D. Madison (1991)
Science 254, 1503-1506
   Abstract »    PDF »
Structure and Regulation of Type II Calcium/Calmodulin-dependent Protein Kinase in Central Nervous System Neurons.
M.B. Kennedy, M.K. Bennett, R.F. Bulleit, N.E. Erondu, V.R. Jennings, S.G. Miller, S.S. Molloy, B.L. Patton, and L.J. Schenker (1990)
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   Abstract »    PDF »
Long-term Potentiation: Presynaptic Enhancement following Postsynaptic Activation of Ca++-dependent Protein Kinases.
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Cold Spring Harb Symp Quant Biol 55, 147-159
   Abstract »    PDF »
Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons.
P Sah, S Hestrin, and R. Nicoll (1989)
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   Abstract »    PDF »
Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP.
R Malinow, H Schulman, and R. Tsien (1989)
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   Abstract »    PDF »
A pertussis toxin-sensitive G protein in hippocampal long-term potentiation.
J. Goh and P. Pennefather (1989)
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Marking synaptic activity in dendritic spines with a calpain substrate exhibiting fluorescence resonance energy transfer.
P. W. Vanderklish, L. A. Krushel, B. H. Holst, J. A. Gally, K. L. Crossin, and G. M. Edelman (2000)
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