A new study has identified a number of genes that are repressed at various time points after memory formation, providing important clues as to how long-term memories are formed.

Storing a persistent memory in the brain involves dynamic gene regulation. However, scientists' knowledge of the target genes controlled during memory formation is limited.

To gain more insights into the role of genes in memory formation, Jun Cho et al. used ribosome profiling and RNA-sequencing of the mouse hippocampus after contextual fear conditioning, a process in which the mice received a small electric shock in a particular setting, forming a strong memory associating that setting with the shock.

The researchers analyzed the hippocampi of trained mice, those that were conditioned with a memory of fear, as well as some control mice that were not trained, analyzing them at different intervals after conditioning.

Based on the ribosome profiling data, the researchers looked for genes that were being expressed differently in the trained mice, identifying 104 genes in total. Of these genes, nearly half that were being suppressed were regulated by estrogen receptor alpha (ESR1), and their down-regulation was noted by the 30 minute mark.

Further investigation found that inhibition of ESR1 significantly impaired memory formation in mice during two hippocampus-dependent tasks. These results suggest that ESR1 may play a pivotal role in modulating gene-regulatory networks after learning.

Further behavioral analyses found that the gene Nrsn1 acts as a memory suppressor gene.

This study highlights the important role of gene repression suppression in memory formation.

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Credit: [Credit: Masahito Ikawa]