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Science 27 February 1998:
Vol. 279. no. 5355, pp. 1363 - 1368
DOI: 10.1126/science.279.5355.1363
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Reports

Src Activation in the Induction of Long-Term Potentiation in CA1 Hippocampal Neurons

You Ming Lu, John C. Roder, * Jonathan Davidow, Michael W. Salter

Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha -amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.

Y. M. Lu and J. C. Roder, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8, Canada.
J. Davidow and M. W. Salter, Division of Neuroscience, Hospital for Sick Children, and Department of Physiology, University of Toronto, M5G 1X8, Canada. E-mail: mike.salter{at}utoronto.ca
*   To whom correspondence should be addressed. E-mail: roder{at}mshri.on.ca

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