When the brain forms memories of new experiences, the engram cells encode details and recall them when we try to recall a past event. Scientists from the U.S. have shown for the first time how different genes are activated and what kind of epigenetic mechanism underlies different waves of gene expression.
The engram cells are in the hippocampus and other parts of the brain. A number of recent studies have shown that these cells form networks linked to certain memories, and these networks are activated when memories are recalled. However, the molecular mechanism of this process is not fully understood by scientists.
Neurobiologists know that at the very first stage of memory formation, the so-called early genes directly turn into engram cells, but soon return to normal activity level. Scientists at MIT wanted to understand what happens in the process of coordinating the long-term storage of memories. They suggested that these waves could be controlled by epigenetic modifications, that is, chemical changes in chromatin, reports MIT News.
To do this, they used genetically modified mice in which engram cells in the hippocampus were labeled with fluorescent protein. They received a weak shock from the current that the rodents learned to associate with the cell where it occurred. When memories were formed, the hippocampus cells began to glow.
Tracking the glowing neurons, scientists observed that in the very first stage after the formation of memories, many DNA regions underwent chromatin changes. In these regions, it became less dense and DNA more accessible. To the researchers’ surprise, almost all of these regions were in DNA areas where there were no genes. These areas contained non-coding sequences – enchancers. At this stage, chromatin changes did not have any effect on gene expression.
The scientists then analyzed the engram cells five days after memory formation. It turned out that the memories increased, and the three-dimensional structure of the chromatin changed. There was still no gene expression, but the preparation for it was underway.
Then, the scientists returned the mice to the cell, where they were electrocuted to reactivate the memories. These animals had a surge in gene expression, many of which are involved in the synthesis of proteins in synapses, helping neurons to strengthen ties with other neurons. The scientists also found that neuronal dendrites have more branches, which also indicates the strengthening of bonds.
This is the first study that shows at the molecular level that the epigene can be prepared for use. Enchancers need to be prepared first, but their readiness is not enough. We need these regions to interact physically with the genes; this is the second phase. Now we understand that the three-dimensional architecture of the genome plays a very important role in coordinating gene expression.