Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

'Hub' of fear memory formation identified in brain cells

30.09.2008
A protein required for the earliest steps in embryonic development also plays a key role in solidifying fear memories in the brains of adult animals, scientists have revealed. An apparent "hub" for changes in the connections between brain cells, beta-catenin could be a potential target for drugs to enhance or interfere with memory formation.

The results are published online this week and appear in the October issue of Nature Neuroscience.

The protein beta-catenin acts like a Velcro strap, fastening cells' internal skeletons to proteins on their external membranes that connect them with other cells. In species ranging from flies to frogs to mice, it also can transmit early signals that separate an embryo into front and back or top and bottom.

During long-term memory formation, structural changes take place in the synapses – the connections between neurons in the brain, says Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. Ressler is a researcher at Emory University's Yerkes National Primate Research Center, where the research was conducted, and a Howard Hughes Medical Institute investigator.

"We thought beta-catenin could be a hub for the changes that take place in the synapses during memory formation," says Ressler. "But because beta-catenin is so important during development, we couldn't take the standard approach of just knocking it out genetically."

He and graduate student Kimberly Maguschak used a variety of approaches to probe beta-catenin's role in fear memory formation, such as stabilizing the protein with a pulse of the psychiatric drug lithium and injecting a virus that could remove the gene for beta-catenin from brain cells.

If mice are electrically shocked just after they hear a certain tone, they gradually learn to fear that tone, and they show that fear by freezing.

To test beta-catenin's involvement in fear memory, Maguschak used a genetically engineered virus paired with mice that had the DNA around their beta-catenin genes modified. Once a cell is infected, the virus deletes the beta-catenin gene so that the cell can't make beta-catenin protein. She injected the virus into the amygdala, a part of the brain thought to be important for forming memories of emotionally charged events.

"We found that after beta-catenin is taken out, the mice can still learn to fear the shocks," says Maguschak. "But two days later, their fear doesn't seem to be retained because they spend half as much time freezing in response to the tone."

Beta-catenin appears to be turned on in the amygdala and involved in signaling during the learning process, Maguschak says.

"However, after the process of moving memories from short-term to long-term is complete, beta-catenin doesn't appear to be necessary anymore," she notes. "Injecting the virus after that point has no effect on the ability of the mice to express their fear memory."

Maguschak also found that lithium salts, when given to the mice before training, make them even more afraid of the tone two days later. Chemically, lithium inhibits an enzyme that usually targets beta-catenin for destruction, causing beta-catenin to become more active. She cautions that lithium is an imprecise tool for studying beta-catenin because it affects several enzymes in the brain.

"Psychiatrists have used lithium to treat mania and bipolar disorder for decades, but how it works is not well-understood," Ressler says. "Importantly, we gave the mice one acute dose of lithium, rather than letting it build to a stable level like in the clinical situation. It's not clear whether there is a connection between mood regulation and how lithium functions in our experiments with fear memory."

The authors suggest medications that inhibit beta-catenin could transiently interfere with memory formation after trauma, helping to prevent post-traumatic stress disorder. Conversely, drugs that enhance beta-catenin function within the brain might serve as new therapies to treating disorders of memory, such as Alzheimer's disease. Besides lithium, no drugs that target beta-catenin are available.

Ressler says his team's next step is to dissect the contribution of beta-catenin's different functions: cell adhesion and developmental signaling. He notes that when over-activated by genetic mutations, beta-catenin can drive tumor formation in several tissues, such as the colon, the skin and the kidney.

"It's possible we will see that a number of genes involved in cancer also are involved in learning and memory," he says.

Kathi Baker | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>