Featured Research

from universities, journals, and other organizations

Turn It Off To Turn It On: Neuroscientists Discover Critical Early Step Of Memory Formation

Date:
September 15, 2008
Source:
Johns Hopkins Medical Institutions
Summary:
Researchers have found how nerve cells in the brain ensure that Arc, a protein critical for memory formation, is made instantly after nerve stimulation. Paradoxically, its manufacture involves two other proteins -- including one linked to mental retardation -- that typically prevent proteins from being made.

Researchers at the Johns Hopkins University School of Medicine report in the journal Neuron how nerve cells in the brain ensure that Arc, a protein critical for memory formation, is made instantly after nerve stimulation. Paradoxically, its manufacture involves two other proteins — including one linked to mental retardation — that typically prevent proteins from being made.

Previous research already established that long-term memory formation depends on Arc protein, but scientists did not know the mechanism that turned on this process.

To find it, they surveyed proteins in mouse brains that change or are activated after a nerve is stimulated and identified eEF2K (short for eukaryotic elongation factor 2 kinase) as a player. When turned on, eEF2K inhibits an important step of protein translation.

"This seemed strange, because it suggested that nerve cells might make Arc protein by using pathways typically thought to turn off protein manufacture," says Paul Worley, M.D., a professor of neuroscience in the Johns Hopkins University School of Medicine.

Further examination of mouse brain slices lacking eEF2K in their nerve cells showed that when stimulated, such cells fail to make the usual pools of Arc protein, demonstrating that eEF2K is required for making Arc.

What it didn't tell them was whether eEF2K specifically was responsible, or whether some other pathway is also involved, so researchers next treated the brain slices from normal mice with a chemical that inhibits protein manufacture by the same mechanism as eEF2K. At the same time that general protein synthesis was turned down, Arc translation actually increased, making it clear eEF2K, through its ability to turn down protein manufacture, somehow enabled a nerve cell to make Arc in response to nerve stimulation.

Meanwhile, Worley's team proceeded to build on research showing that a protein linked to a form of mental retardation passed on by an abnormal "fragile X" chromosome also represses the manufacture of some proteins. The researchers looked at Arc protein levels in nerve cells lacking the fragile X mental retardation protein and found stable levels of Arc protein all the time, before, during, after and even without stimulation of the nerve cells. They concluded that without fragile X protein, the presumed "brakes" on the system, the manufacture of Arc goes unregulated.

"It's sort of a seesaw relationship," Worley says. When nerve cells are stimulated, eEF2K is activated to suppress protein manufacture generally, thereby allowing for the rapid manufacture of Arc, and, at the same time, fragile X mental retardation protein is stimulated to let Arc protein get made.

"By defining a mechanism that is associated with fragile X syndrome — the most common inherited cause of mental retardation and autism — it may help others to identify potential therapeutic targets to help with the disease," Worley says.

The research was funded by the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute on Aging.

Authors on the paper are Sunjin Park, Joo Min Park, Sangmok Kim, Jin-Ah Kim, Jason D. Shepherd, Constance L. Smith-Hicks, Shoaib Chowdhury, Walter Kaufmann, Dietmar Kuhl, Alexey G. Ryazanov, Richard L. Huganir, David J. Linden, and Worley, all of Hopkins.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. Park et al. Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD. Neuron, 2008; 59 (1): 70 DOI: 10.1016/j.neuron.2008.05.023

Cite This Page:

Johns Hopkins Medical Institutions. "Turn It Off To Turn It On: Neuroscientists Discover Critical Early Step Of Memory Formation." ScienceDaily. ScienceDaily, 15 September 2008. <www.sciencedaily.com/releases/2008/09/080915105819.htm>.
Johns Hopkins Medical Institutions. (2008, September 15). Turn It Off To Turn It On: Neuroscientists Discover Critical Early Step Of Memory Formation. ScienceDaily. Retrieved April 15, 2014 from www.sciencedaily.com/releases/2008/09/080915105819.htm
Johns Hopkins Medical Institutions. "Turn It Off To Turn It On: Neuroscientists Discover Critical Early Step Of Memory Formation." ScienceDaily. www.sciencedaily.com/releases/2008/09/080915105819.htm (accessed April 15, 2014).

Share This



More Health & Medicine News

Tuesday, April 15, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com
How Mt. Everest Helped Scientists Research Diabetes

How Mt. Everest Helped Scientists Research Diabetes

Newsy (Apr. 15, 2014) British researchers were able to use Mount Everest's low altitudes to study insulin resistance. They hope to find ways to treat diabetes. Video provided by Newsy
Powered by NewsLook.com
Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Newsy (Apr. 14, 2014) Richard van As lost all fingers on his right hand in a woodworking accident. Now, he's used the incident to create a prosthetic to help hundreds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins