Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning
| Autor: | Daniel L. Alkon, Herman Epstein, Alan Kuzirian, M. Catherine Bennett, Thomas J. Nelson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Proteasome Endopeptidase Complex
Indoles Multidisciplinary Bryostatin 1 Activator (genetics) Kinase Hermissenda Biological Sciences Biology Bryostatins Immunohistochemistry Associative learning GTP-binding protein regulators Biochemistry Downregulation and upregulation GTP-Binding Proteins Memory Protein Biosynthesis Protein biosynthesis Animals Learning Pyrroles Macrolides Protein Kinase C Protein kinase C |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:16432-16437 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0508001102 |
| Popis: | Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo prolonged activation after associative learning. Under normal conditions, two training events with paired visual and vestibular stimuli cause short-term memory of the mollusc Hermissenda that lasts ≈7 min. However, after 4-h exposures to Bryo (0.25 ng/ml) on two preceding days, the same two training events produced long-term conditioning that lasted >1 week and that was not blocked by anisomycin (1 μg/ml). Anisomycin, however, eliminated long-term memory lasting at least 1 week after nine training events. Both the nine training events alone and two Bryo exposures plus two training event regimens caused comparably increased levels of the PKC α-isozyme substrate calexcitin in identified type B neurons and enhanced PKC activity in the membrane fractions. Furthermore, Bryo increased overall protein synthesis in cultured mammalian neurons by up to 60% for >3 days. The specific PKC antagonist Ro-32-0432 blocked much of this Bryo-induced protein synthesis as well as the Bryo-induced enhancement of the behavioral conditioning. Thus, Bryo-induced PKC activation produces those proteins necessary and sufficient for long-term memory on days in advance of the training events themselves. |
| Databáze: | OpenAIRE |
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