Ras acts as a molecular switch between two forms of consolidated memory in Drosophila
| Autor: | Erica Walkinshaw, Nathaniel C. Noyes, Ronald L. Davis |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
animal structures Inhibitory postsynaptic potential 03 medical and health sciences 0302 clinical medicine Memory Extracellular Animals Drosophila Proteins Mushroom Bodies Memory Consolidation Neurons Gene knockdown Multidisciplinary biology Chemistry Kinase fungi Biological Sciences Impaired memory biology.organism_classification Phenotype Cell biology Proto-Oncogene Proteins c-raf Drosophila melanogaster 030104 developmental biology Mushroom bodies ras Proteins psychological phenomena and processes 030217 neurology & neurosurgery |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1819925117 |
| Popis: | Long-lasting, consolidated memories require not only positive biological processes that facilitate long-term memories (LTM) but also the suppression of inhibitory processes that prevent them. The mushroom body neurons (MBn) in Drosophila melanogaster store protein synthesis-dependent LTM (PSD-LTM) as well as protein synthesis-independent, anesthesia-resistant memory (ARM). The formation of ARM inhibits PSD-LTM but the underlying molecular processes that mediate this interaction remain unknown. Here, we demonstrate that the Ras→Raf→rho kinase (ROCK) pathway in MBn suppresses ARM consolidation, allowing the formation of PSD-LTM. Our initial results revealed that the effects of Ras on memory are due to postacquisition processes. Ras knockdown enhanced memory expression but had no effect on acquisition. Additionally, increasing Ras activity optogenetically after, but not before, acquisition impaired memory performance. The elevated memory produced by Ras knockdown is a result of increased ARM. While Ras knockdown enhanced the consolidation of ARM, it eliminated PSD-LTM. We found that these effects are mediated by the downstream kinase Raf. Similar to Ras, knockdown of Raf enhanced ARM consolidation and impaired PSD-LTM. Surprisingly, knockdown of the canonical downstream extracellular signal-regulated kinase did not reproduce the phenotypes observed with Ras and Raf knockdown. Rather, Ras/Raf inhibition of ROCK was found to be responsible for suppressing ARM. Constitutively active ROCK enhanced ARM and impaired PSD-LTM, while decreasing ROCK activity rescued the enhanced ARM produced by Ras knockdown. We conclude that MBn Ras/Raf inhibition of ROCK suppresses the consolidation of ARM, which permits the formation of PSD-LTM. |
| Databáze: | OpenAIRE |
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