Navigation Links
'Hub' of fear memory formation identified in brain cells
Date:9/28/2008

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.


'/>"/>

Contact: Kathi Baker
kobaker@emory.edu
404-727-9371
Emory University
Source:Eurekalert

Related medicine news :

1. Joint NJ/NY Rally for Addiction Recovery to Be Hub of Events Nationwide
2. Chubby Checker Adds Twist to 10,000 Strong at Ninth Annual Walk to Cure Cancer for UMass Memorial Cancer Center at the UMass Medical School
3. Federal Labor Law Violations Provoke Teamster Strike at AmerisourceBergen Northwest Distribution Hub
4. Founding CEOS of SureScripts(R) and RxHub(R) Join Forces to Deliver Clinical Information Technology Services to Physician Practices
5. Epilepsy marked by neural hub network
6. Baker Energy and Huber Receive First-of-its-Kind Award from Wyoming Department of Environmental Quality
7. AVMA Launches Animal Welfare Web Section to Provide Hub for Programs and Information
8. Chubb Expects to Release Earnings on July 24 and Hold Conference Call on the Same Day
9. HUB International New England Reminds Massachusetts Boaters that Safety is Paramount This Summer
10. New Alzheimers findings: High stress and genetic risk factor lead to increased memory decline
11. Removing Ovaries Before Menopause Leads to Memory, Movement Troubles
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned ... developed to enhance the health of felines. The formula is all-natural and is made ... in the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library ... City Observer , brings up a new, often overlooked aspect of head lice: the parasite’s ... for fumigation is not a common occurrence, but a necessary one in the event that ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... On Friday, ... presented a Bronze Wellness at Work award to iHire in recognition of their exemplary ... part of the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. Her ... would lash out at his family verbally and physically. , “When something upset him, he ... he would use it. He would throw rocks at my other children and say he ...
(Date:6/24/2016)... NY (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin ... companies that call for a minimum wage raise to $12 an hour by 2020 and ... This will restore the lost value of the minimum wage, assure the wage floor does ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016 The Academy of Managed Care ... that would allow biopharmaceutical companies to more easily ... make formulary and coverage decisions, a move that addresses ... medicines. The recommendations address restrictions in the ... the drug label, a prohibition that hinders decision makers ...
(Date:6/24/2016)... -- According to a new market research ... Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, 8mm, ... Purchase (Retail, Non-Retail) - Trends & Global Forecasts to ... for the forecast period of 2016 to 2021. This ... 2021 from USD 1.65 Billion in 2016, growing at ...
(Date:6/23/2016)... -- MedSource announced today that it has selected Datatrial,s ... choice.  This latest decision demonstrates MedSource,s commitment to ... by offering a state-of-the-art electronic data capture (EDC) ... the EDC platform of choice in exchange for ... long been a preferred EDC platform by our ...
Breaking Medicine Technology: