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The Journal of Neuroscience, July 2, 2003, 23(13):5503-5506
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BRIEF COMMUNICATION
Postsynaptic Density-95 Mimics and Occludes Hippocampal Long-Term Potentiation and Enhances Long-Term Depression
Valentin Stein,1 David R. C. House,1 David S. Bredt,2 andRoger A. Nicoll1,2 Departments of 1Cellular and Molecular Pharmacology, and 2Physiology, University of California, San Francisco, California 94143
Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity.
Key words: PSD-95; AMPA receptors; long-term potentiation; long-term depression; hippocampus; silent synapses
Received Mar. 14, 2003; revised Apr. 24, 2003; accepted Apr. 28, 2003.
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