AsianScientist (Oct. 13, 2015) – By combining ribosome profiling (RPF) with RNA sequencing, researchers have made the surprising finding that gene repression plays an important role in memory formation in the hippocampus. Their results have been published in Science.
The formation of memories is a complex process that is thought to be controlled by the translation of proteins in the brain. However, the lack of tools able to accurately and precisely compare the levels of transcription and translation has prevented scientists from understanding which genes are involved and how they are regulated during memory consolidation.
In the present study, researchers from the Institute of Basic Science and Seoul National University have used RPF and RNA sequencing to create a comprehensive map of both the transcriptome and translatome before and after memory formation. By normalizing the information on mRNA translation obtained by RPF against the mRNA levels determined by RNA sequencing in parallel, they were able to determine the translation efficiency of each mRNA sequence.
They found that there were three waves of repressive regulation involved in memory suppression: the basal suppression of ribosomal protein-coding genes, rapid repression of specific genes induced by learning and the late persistent suppression through the inhibition of estrogen receptor 1 (ESR1/ERα).
In contrast to the widely held belief that memory formation relied on protein formation in the brain, the research group demonstrated that the mouse hippocampi showed extremely low level of basal translation as evidenced by fewer amount of proteins that constitute ribosomes, the organelle responsible for translating mRNA into protein. Additionally, when they compared the ribosomal levels from other organs (livers, testes and kidneys) in the mice to the hippocampus, there was once again a deficit.
“Some of these genes might be ‘memory suppressor genes’ that need to be downregulated for memory formation,” study first author Dr. Jun Cho explained.
Their analysis also showed that genes such as Nrsn1 were rapidly repressed after contextual fear conditioning, with mRNA levels decreasing within five to ten minutes. When Nrsn1 was overexpressed in the hippocampus, the mice showed deficits in long-term memory formation, possibly explaining why Nrsn1 is downregulated during learning.
“Our study illustrates the potential importance of negative gene regulation in learning and memory,” Cho added.
The article can be found at: Cho et al. (2015) Multiple Repressive Mechanisms in the Hippocampus During Memory Formation.
———
Source: Institute for Basic Science.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
