Featured Research

from universities, journals, and other organizations

Scientists map process by which brain cells form long-term memories

Date:
June 9, 2013
Source:
Gladstone Institutes
Summary:
Scientists have deciphered how a protein called Arc regulates the activity of neurons -- providing much-needed clues into the brain's ability to form long-lasting memories. These findings also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.

Artist's rendering of brain cells.
Credit: Giovanni Cancemi / Fotolia

Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons -- providing much-needed clues into the brain's ability to form long-lasting memories. These findings, reported today in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.

Led by Gladstone Senior Investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories. However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.

Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called "homeostatic scaling." Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they've made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.

"Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day," said Dr. Finkbeiner, who is also a professor of neurology and physiology at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc's presence at these synapses was driving the formation of long-lasting memories."

But Dr. Finkbeiner and his team thought there was something else in play. In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc's movements. And what they found was surprising.

"When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses -- but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus," said Erica Korb, PhD, the paper's lead author who completed her graduate work at Gladstone and UCSF. "A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there. The presence of this complex and tightly regulated system is strong evidence that this process is biologically important."

In fact, the team's experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories. From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them -- thus translating learning into long-term memories.

"This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself -- disruptions in which have already been implicated in a whole host of neurological diseases," said Dr. Finkbeiner. "For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain's memory center, in Alzheimer's disease patients. It's possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer's."

Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome -- a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.

"In the future," added Dr. Korb, "we hope further research into Arc's role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them."

Support for this research was provided by a Ruth L. Kirschstein Fellowship, the National Institute of Neurological Disease and Stroke, the National Institute on Aging and the Keck Foundation.


Story Source:

The above story is based on materials provided by Gladstone Institutes. Note: Materials may be edited for content and length.


Journal Reference:

  1. Erica Korb, Carol L Wilkinson, Ryan N Delgado, Kathryn L Lovero, Steven Finkbeiner. Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Nature Neuroscience, 2013; DOI: 10.1038/nn.3429

Cite This Page:

Gladstone Institutes. "Scientists map process by which brain cells form long-term memories." ScienceDaily. ScienceDaily, 9 June 2013. <www.sciencedaily.com/releases/2013/06/130609195704.htm>.
Gladstone Institutes. (2013, June 9). Scientists map process by which brain cells form long-term memories. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2013/06/130609195704.htm
Gladstone Institutes. "Scientists map process by which brain cells form long-term memories." ScienceDaily. www.sciencedaily.com/releases/2013/06/130609195704.htm (accessed July 31, 2014).

Share This




More Mind & Brain News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dieting At A Young Age Might Lead To Harmful Health Habits

Dieting At A Young Age Might Lead To Harmful Health Habits

Newsy (July 30, 2014) Researchers say women who diet at a young age are at greater risk of developing harmful health habits, including eating disorders and alcohol abuse. Video provided by Newsy
Powered by NewsLook.com
It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. 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