Reveal the hidden cellular logistics of neuronal memory

In this representation, the red background is the cytosol and the ribosomes are light green. tRNA is a purplish blue mass. Some tRNAs are in the cytosol and others are bound to green ribosomes. mRNA is represented in yellow. The thin purple chains that emerge from the opposite side of the ribosome (and into the endoplasmic reticulum cavity) are proteins. The large thick black line in the lower left corner represents the lipid bilayer of the ER membrane. Credit: Sara Aton

A team of cell biologists at the University of Michigan (UM) investigated the mechanisms involved in sleep-dependent memory and memory, and RNA associated with poorly studied cellular compartments of hippocampal neurons was found in post-learning sleep mice. We have found significant differences between sleep-deficient mice.

Sarah Atton, an associate professor of molecular cell developmental biology, and James Delorme, a recent graduate student in UM neuroscience, found that both learning events and subsequent sleep (or sleep loss) affect mRNA translation. I assumed to give. Most of the studies to date on the effects of sleep on mRNA have focused on transcripts of the neurocytosolic sol. But doctor. After learning, Aton and Delorme instead discovered that major changes in RNA were (almost exclusively) present in the ribosomes associated with the nerve cell membrane. These results are Minutes of the National Academy of Sciences, November 30, 2021.

The team first applied a commonly used biochemical method to homogenize and centrifuge the hippocampal tissue into the cytosol, an aqueous component of the cytoplasm of cells in which small organelles and particles are suspended. Was isolated from other cellular components that are usually considered “fragments”. ((((Endoplasmic reticulum, Golgi apparatus, Cell membrane, NS. ). In this study, the authors found that the RNA associated with the cytosol ribosomes differed depending on whether the animal slept, confirming previous transcriptome studies. However, cytosol ribosomes showed little RNA change in response to prior learning.

“When I stopped there, I couldn’t find anything new and insightful. I strongly felt the need to rethink the methodology,” Aton explains. Since it is well known that the endoplasmic reticulum is covered with ribosomes, Delorme and Aton, the mechanisms that convert RNA into proteins, produce RNA in “fragments” that are other parts of the cell outside the cytosol. I decided to decide the sequence. It is the less well-studied membrane-containing cell fraction that they found that many transcripts were affected as a function of prior learning. These modified transcripts also differed greatly in whether the animals were allowed to sleep after learning (whether they were able to preserve new memories) or whether they were sleep deprived. These unexpected results open the door to more research.

“By examining other areas of the cell, we can make many new hypotheses about what happens at the molecular level when memory is integrated and when integration is interrupted due to sleep deprivation. “It’s now,” said Aton.

For example, in animals that slept after learning, Aton and Delorme observed an increase in the amount of transcripts encoding components of the protein synthesis mechanism in the membrane fraction of hippocampal neurons. One hypothesis is to test whether membrane-bound ribosomes actually increase protein production after sleep after learning.

In addition to mRNA, the authors also found that learning results in changes in the association between long non-coding RNAs and neural cell membrane-bound ribosomes. These may play a role in regulating the translation of other transcripts that need to be investigated. “NS cell We are developing highly sophisticated mechanisms for fine-tuning the process from transcription to translation, and long non-coding RNAs can be one of them in this part of the brain, “Aton said. I am saying.

She further explained by comparing neurons to a large warehouse. Complex logistics are needed to quickly respond to the needs of new proteins in remote cell processes, requiring preparation and distribution adaptation processes. “Neurons need to deliver’packages’ when and when they need them, within a reasonable time frame, no matter how far away they are. Neurons have evolved to do this, and investigating is a major biological problem. It’s important to understand. In addition to preserving new memory, how this biology works because it affects regeneration, degeneration, and neurological disorders, “Aton concludes.

This is the second PNAS A publication from a study by the Delorme-Aton team. In their first articleThe team discovered an inhibitory gating mechanism that could disrupt hippocampal activity and memory integration in sleep-deprived mice.In contrast, post-learning sleep suppressed the activity of inhibitory interneurons and increased the activity of their surroundings. Hippocampal neurons, And improved memory storage.

How sleep loss interferes with hippocampal new memory

For more information:
James Delorme et al, the cytosol and membrane-bound ribosome transcriptional profile of hippocampal neurons are regulated differently by learning and subsequent sleep. Minutes of the National Academy of Sciences (2021). DOI: 10.1073 / pnas.2108534118

James Delorme et al, sleep loss promotes hippocampal activity gating through acetylcholine and somatostatin interneurons and inhibits memory enhancement. Minutes of the National Academy of Sciences (2021). DOI: 10.1073 / pnas.2019318118

Quote: Https: // Announcement of Hidden Cellular Logistics for Neuronal Memory Storage Obtained on November 25, 2021 November 25, 2021)

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Reveal the hidden cellular logistics of neuronal memory

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