Brain Cell DNA Refolds Itself to Aid Memory Recall (Quanta)
More than a century ago, the zoologist Richard Semon coined the term “engram” to designate the physical trace a memory must leave in the brain, like a footprint. Since then, neuroscientists have made progress in their hunt for exactly how our brains form memories. They have learned that specific brain cells activate as we form a memory and reactivate as we remember it, strengthening the connections among the neurons involved. That change ingrains the memory and lets us keep memories we recall more often, while others fade. But the precise physical alterations within our neurons that bring about these changes have been hard to pin down — until now.
In a study published last month, researchers at the Massachusetts Institute of Technology tracked an important part of the memory-making process at the molecular scale in engram cells’ chromosomes. Neuroscientists already knew that memory formation is not instantaneous, and that the act of remembering is crucial to locking a memory into the brain. These researchers have now discovered some of the physical embodiment of that mechanism.
The MIT group worked with mice that had a fluorescent marker spliced into their genome to make their cells glow whenever they expressed the gene Arc, which is associated with memory formation. The scientists placed these mice in a novel location and trained them to fear a specific noise, then returned them to this location several days later to reactivate the memory. In the brain area called the hippocampus, the engram cells that formed and recalled this memory lit up with color, which made it easy to sort them out from other brain cells under the microscope during a postmortem examination.
Peering into the nuclei of these engram cells, the researchers spotted fine-grained changes in the architecture of the chromatin — the complex of DNA and regulatory proteins that makes up chromosomes — as the memory took shape. Parts of the chromatin reorganized in such a way that memory-associated genes could more easily spring into action to strengthen and preserve a memory. “Basically, the entire memory formation process is a priming event,” said Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the senior author on the study.
Warming Up for a Memory
This conclusion wasn’t clear from the beginning of the experiment. Right after the memory formed, there weren’t huge differences in how the engram cells expressed their genes. But the researchers did notice some structural changes to the cells’ chromatin: Certain regions of the DNA became more accessible, shifting so that chromatin proteins and other stretches of DNA weren’t covering them up. This made the genes in that DNA more accessible to enhancers, genetic elements that can increase the activation of genes.
***
more: https://www.quantamagazine.org/brain-cell-dna-refolds-itself-to-aid-memory-recall-20201102/
https://www.nature.com/articles/s41593-020-00717-0 (publiic abstract, article behind paywall)
= new reply since forum marked as read
