Epigenetic Mechanism behind Memory Recall

 Epigenetic Mechanism behind Memory Recall

    Memories are often talked about in forms of sentimentality and knowledge. Recollections one shared with their loved ones or retained vocabulary words of a subject are all parts of our memory. It is not doubt that memories are essential part of our lives and contribute significantly to who we are. Brain disorders, such as Alzheimer’s disease, will lead to memory loss and loss of connections between networks mainly due to degeneration of neurons. Many studies have been conducted in attempt to understand the biology of memory consolidation and memory retrieval as it greatly influences our quality of life. A recent study at MIT shows that large scale modifications of proteins and DNA that codes for cells’ chromatin is responsible for the way engram neurons encode memories. In the paper, “Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble” by Li-Huei Tsai et al. explores the epigenetic mechanism behind the waves of gene expression for memory. 

 

    Hippocampus plays a major role in memory consolidation and memory retrieval. Engram neurons are abundant in many parts of the brain as well as the hippocampus. These neurons are responsible for establishing networks associated with specific memories. When a specific memory is recalled, the networks associated with that memory is activated. During the memory formation and consolidation, connections between neurons are made stronger and faster through the waves of gene expression and specific protein synthesis. The researchers at MIT went furthermore into exploring the molecular modifications that could potentially control these waves of gene expression. Different regions of DNA experience chromatin modifications after memory formation. DNA become more accessible as chromatin loosen during the chromatin modifications. It is interesting to note that most of the regions of DNA that are becoming accessible were where genes are not present. These stretches of DNA are known as enhancers, which are controlled by genes. 

 

    Researchers used genetically modified mice, whose engram cells in the hippocampus are tagged with a fluorescent protein, for this experiment. The experiment involves a mild shock to the mice’s foot, which they will associate with the cage they received the shock. Hippocampal cells will produce a yellow fluorescent protein marker when the memory connection is established. Once marked, those neurons can be track endlessly. When the mice are placed back into the cage where they initially received the shock, fearful memory was activated. Upon activation, researchers noticed a rise in the expression of the targeted genes that the primed enhancers consistently interact with. It is important to note that during memory consolidation, the chromatin modifications happening around the enhancers only bring the enhancers closer to the target genes. Bring the enhancers closer to the target genes does not turn those genes on, the enhancers were only primed to activate gene expression when a memory is recalled. 

 

    Fearful memory is one of the extensively studied memory for evolutionary reasons. In this experiment, fearful memory is used for recall. The study, led by Stephanie L. Grella, on odor in association with memory investigate the role odor plays in the modification of temporal dynamics. It will be interesting to explore how odor can influence the epigenetic mechanism and whether chromatins are loosened more with the involvement of odor at the time of encoding. Epigenomic modifications are essential for memory recall, but fear and odor seem to be two factors that can contribute to intense remote memory recall.

 

 

References

 

Grella, Stephanie L., et al. “Stephanie L. Grella.” Learning & Memory, Cold Spring Harbor Lab, 31 Dec. 2019, http://learnmem.cshlp.org/content/27/4/150.short. 

Tsai, Li-Huei, et al. “Mapping the Epigenomic and Transcriptomic Interplay during Memory Formation and Recall in the Hippocampal Engram Ensemble.” Nature News, Nature Publishing Group, 5 Oct. 2020, https://www.nature.com/articles/s41593-020-00717-0.