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

TitleAn essential role for protein phosphatases in hippocampal long-term depression.
Publication TypeJournal Article
Year of Publication1993
AuthorsMulkey RM, Herron CE, Malenka RC
Date Published1993 Aug 20
KeywordsAnimals, Calcium, Calmodulin, Electric Stimulation, Ethers, Cyclic, Hippocampus, Microcystins, Okadaic Acid, Oxazoles, Peptides, Cyclic, Phosphoprotein Phosphatases, Phosphorylation, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Synapses, Synaptic Transmission

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.

Alternate JournalScience
PubMed ID8394601
Grant ListMH00942 / MH / NIMH NIH HHS / United States
MH10306 / MH / NIMH NIH HHS / United States
MH45334 / MH / NIMH NIH HHS / United States