Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

How Old Memories Fade Away

Published: Friday, September 20, 2013
Last Updated: Friday, September 20, 2013
Bookmark and Share
Discovery of a gene essential for memory extinction could lead to new PTSD treatments.

If you got beat up by a bully on your walk home from school every day, you would probably become very afraid of the spot where you usually met him. However, if the bully moved out of town, you would gradually cease to fear that area.

Neuroscientists call this phenomenon “memory extinction”: Conditioned responses fade away as older memories are replaced with new experiences.

A new study from MIT reveals a gene that is critical to the process of memory extinction. Enhancing the activity of this gene, known as Tet1, might benefit people with posttraumatic stress disorder (PTSD) by making it easier to replace fearful memories with more positive associations, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory.

The Tet1 gene appears to control a small group of other genes necessary for memory extinction. “If there is a way to significantly boost the expression of these genes, then extinction learning is going to be much more active,” says Tsai, the Picower Professor of Neuroscience at MIT and senior author of a paper appearing in the Sept. 18 issue of the journal Neuron.

The paper’s lead authors are Andrii Rudenko, a postdoc at the Picower Institute, and Meelad Dawlaty, a postdoc at the Whitehead Institute.

New and old memories

Tsai’s team worked with researchers in Rudolf Jaenisch’s lab at the Whitehead to study mice with the Tet1 gene knocked out. Tet1 and other Tet proteins help regulate the modifications of DNA that determine whether a particular gene will be expressed or not. Tet proteins are very abundant in the brain, which made scientists suspect they might be involved in learning and memory.

To their surprise, the researchers found that mice without Tet1 were perfectly able to form memories and learn new tasks. However, when the team began to study memory extinction, significant differences emerged.

To measure the mice’s ability to extinguish memories, the researchers conditioned the mice to fear a particular cage where they received a mild shock. Once the memory was formed, the researchers then put the mice in the cage but did not deliver the shock. After a while, mice with normal Tet1 levels lost their fear of the cage as new memories replaced the old ones.

“What happens during memory extinction is not erasure of the original memory,” Tsai says. “The old trace of memory is telling the mice that this place is dangerous. But the new memory informs the mice that this place is actually safe. There are two choices of memory that are competing with each other.”

In normal mice, the new memory wins out. However, mice lacking Tet1 remain fearful. “They don’t relearn properly,” Rudenko says. “They’re kind of getting stuck and cannot extinguish the old memory.”

In another set of experiments involving spatial memory, the researchers found that mice lacking the Tet1 gene were able to learn to navigate a water maze, but were unable to extinguish the memory.

Control of memory genes

The researchers found that Tet1 exerts its effects on memory by altering the levels of DNA methylation, a modification that controls access to genes. High methylation levels block the promoter regions of genes and prevent them from being turned on, while lower levels allow them to be expressed.

Many proteins that methylate DNA have been identified, but Tet1 and other Tet proteins have the reverse effect, removing DNA methylation. The MIT team found that mice lacking Tet1 had much lower levels of hydroxymethylation — an intermediate step in the removal of methylation — in the hippocampus and the cortex, which are both key to learning and memory.

These changes in demethylation were most dramatic in a group of about 200 genes, including a small subset of so-called “immediate early genes,” which are critical for memory formation. In mice without Tet1, the immediate early genes were very highly methylated, making it difficult for those genes to be turned on.

In the promoter region of an immediate early gene known as Npas4 — which Yingxi Li, the Frederick A. and Carole J. Middleton Career Development Assistant Professor of Neuroscience at MIT, recently showed regulates other immediate early genes — the researchers found methylation levels close to 60 percent, compared to 8 percent in normal mice.

“It’s a huge increase in methylation, and we think that is most likely to explain why Npas4 is so drastically downregulated in the Tet1 knockout mice,” Tsai says.

Keeping genes poised

The researchers also discovered why the Tet1-deficient mice are still able to learn new things. During fear conditioning, methylation of the Npas4 gene goes down to around 20 percent, which appears to be low enough for the expression of Npas4 to turn on and help create new memories. The researchers suspect the fear stimulus is so strong that it activates other demethylation proteins — possibly Tet2 or Tet3 — that can compensate for the lack of Tet1.

During the memory-extinction training, however, the mice do not experience such a strong stimulus, so methylation levels remain high (around 40 percent) and Npas4 does not turn on.

The findings suggest that a threshold level of methylation is necessary for gene expression to take place, and that the job of Tet1 is to maintain low methylation, ensuring that the genes necessary for memory formation are poised and ready to turn on at the moment they are needed.

The researchers are now looking for ways to increase Tet1 levels artificially and studying whether such a boost could enhance memory extinction. They are also studying the effects of eliminating two or all three of the Tet enzymes.

“This will not only help us further delineate epigenetic regulation of memory formation and extinction, but will also unravel other potential functions of Tets and methylation in the brain beyond memory extinction,” Dawlaty says.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Wednesday, April 27, 2016
Why Some Tumors Withstand Treatment
Mechanism uncovered that allows cancer cells to evade targeted therapies.
Thursday, March 17, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Faster Drug Discovery?
Startup develops more cost-effective test for assessing how cells respond to chemicals.
Friday, January 29, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
Tracing a Cellular Family Tree
New technique allows tracking of gene expression over generations of cells as they specialize.
Wednesday, January 06, 2016
New Device Uses Carbon Nanotubes to Snag Molecules
Nanotube “forest” in a microfluidic channel may help detect rare proteins and viruses.
Tuesday, December 22, 2015
Scaling Up Synthetic-Biology Innovation
MIT professor’s startup makes synthesizing genes many times more cost effective.
Monday, December 14, 2015
“Kill Switches” Shut Down Engineered Bacteria
Synthetic biology technique could make it safer to put engineered microbes to work outside of the lab.
Monday, December 14, 2015
Drug-Resistance Mechanism in Tumor Cells Unravelled
Targeting the RNA-binding protein that promotes resistance could lead to better cancer therapies.
Friday, October 23, 2015
Learning About Human Health Using Sewage
PhD student Mariana Matus studies human waste to understand individual and community health.
Thursday, September 17, 2015
Real-Time Data for Cancer Therapy
Biochemical sensor implanted at initial biopsy could allow doctors to better monitor and adjust cancer treatments.
Thursday, August 06, 2015
Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Scientific News
A Guide to CRISPR Gene Activation
A comparison of synthetic gene-activating Cas9 proteins can help guide research and development of therapeutic approaches.
Gene That Lowers Heart Attack Risk Identified
Individuals with a rare twelve-letter deletion from a gene on chromosome 17 have significantly reduced non-HDL cholesterol levels and a 35% lower than average risk of heart disease.
"Sunscreen" Gene May Guard Against Melanoma
USC-led study reveals that melanoma patients with deficient or mutant copies of the gene are less protected from harmful ultraviolet rays.
Myeloid-Derived Suppressor Cells Play Role in Tumor Growth
Researchers at Baylor College of Medicine have reported a new mechanism that helps cancer cells engage myeloid-derived suppressor cells.
Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
Roundup Impacts Gene Expression
Study published on the impact of low-dose toxicity of Roundup weed-killer on gene expression profiles.
US-India Collab Finds Molecular Signatures of Severe Malaria
Study may be a significant advancement in understanding the causes of severe malaria.
Big Data Can Save Lives
The sharing of genetic information from millions of cancer patients around the world could be key to revolutionising cancer prevention and care, according to a leading cancer expert from Queen's University Belfast.
Triple-Negative Breast Cancer Target Is Found
Researchers at UC Berkeley discover a target that drives cancer metabolism in triple-negative breast cancer.
Gene Expression Controls Revealed
Researchers have modelled every atom in a key part of the process for switching on genes, revealing a whole new area for potential drug targets.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!