Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone scientists map process by which brain cells form long-term memories

10.06.2013
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.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.

Anne Holden | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>