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.

Diagram of the midpiece of the spermatozoa.

This study highlights the important role of gene repression suppression in memory formation.eight on a healthier course as they emerge into adulthood,” Asarnow said.

ABOUT THIS NEUROLOGY RESEARCH

Source: Natasha Pinol – AAAS
Image Credit: The image is credited to Masahito Ikawa
Original Research: Abstract for “Multiple repressive mechanisms in the hippocampus during memory formation” by Jun Cho, Nam-Kyung Yu, Jun-Hyeok Choi, Su-Eon Sim, SukJae Joshua Kang, Chuljung Kwak, Seung-Woo Lee, Ji-il Kim, Dong Il Choi, V. Narry Kim, and Bong-Kiun Kaang in Science. Published online October 1 2015 doi:10.1126/science.aac7368


Abstract

Multiple repressive mechanisms in the hippocampus during memory formation

Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.

“Multiple repressive mechanisms in the hippocampus during memory formation” by Jun Cho, Nam-Kyung Yu, Jun-Hyeok Choi, Su-Eon Sim, SukJae Joshua Kang, Chuljung Kwak, Seung-Woo Lee, Ji-il Kim, Dong Il Choi, V. Narry Kim, and Bong-Kiun Kaang in Science. Published online October 1 2015 doi:10.1126/science.aac7368