Scientists have recorded evidence of the Brain Turning Off its Memory Inhibitor to make New Memories

In 1953, a man named Henry Molaison underwent a surgery which removed most of his hippocampus in an attempt to cure his epileptic seizures. The surgery was a qualified success though, because in addition to curing him of seizures he also lost the ability to form new long term memories. It was Molaison’s memory problems that led doctors to conclude that the hippocampus was the part of the brain responsible for long term memory.

IBS Center for RNA Research used a tool called Ribosome profiling (RPF) as well as RNA-seq to analyze mouse hippocampi. In contrast to the widely held belief that memory formation relies on protein formation in the brain, the research group found that the genes encoding hippocampal ribosomal subunits, the organelle responsible for translating mRNA into protein, are translationally suppressed. Additionally, they found that hippocampal levels of translating ribosomes are much lower than those from other organs (livers, testes and kidneys).

They carried out RPF and RNA-seq with the mouse hippocampi after contextual fear conditioning by comparing them to an untested control group after 5,10 and 30 minutes and 4 hours post-conditioning. Through the analysis of the data, the research offers insight into translational and transcriptional regulations in the brain during memory formation at the genomic scale. The observations showed 2 types of repressive events were induced after learning: an initial wave of transient translational regulation at around 5 to 10 min and the suppression of genes through decreases of mRNA levels after 30 minutes, which continued through 4 hours.

Why did this happen? It seems that in order to make new memories, the brain needs to turn off genetic processes which act to inhibit memories from being formed. Nrsn1, one of the newly identified genes undergoing rapid translational repression, may act as a suppressor of long-term memory formation. Additionally, activating estrogen receptor ESR1 in the hippocampus also impaired memory formation.

When an animal experiences no stimulus in an environment the hippocampus undergoes gene repression which prevents the formation of new memories. Upon the introduction of a stimulus, the hippocampus’ repressive gene regulation is turned off allowing for new memory creation. Jun Cho says, “Our study illustrates the potential importance of negative gene regulation in learning and memory”. http://www.alphagalileo.org/ViewItem.aspx?ItemId=156957&CultureCode=en

Neurensin 1 (NRSN1)