Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Scientists Identify Two Molecules that Affect Brain Plasticity in Mice

Published: Tuesday, December 01, 2009
Last Updated: Tuesday, December 01, 2009
Bookmark and Share
Stanford researchers have identified a set of molecular brakes that stabilize the developing brain’s circuitry.

Researchers at the Stanford University School of Medicine have identified a set of molecular brakes that stabilize the developing brain’s circuitry. Moreover, experimentally removing those brakes in mice enhanced the animals’ performance in a test of visual learning, suggesting a long-term path to therapeutic application.

In a study published Nov. 25 in Neuron, Carla Shatz, PhD, professor of neurobiology and of biology, and her colleagues have implicated two members of a large family of proteins critical to immune function (collectively known as HLA molecules in humans and MHC1 molecules in mice) in brain development. Until recently, these immune-associated molecules were thought to play no role at all in the healthy brain.

In previous studies, Shatz and her co-investigators have shown that MHC molecules are found on the surfaces of nerve cells in the brain, and that they temper “synaptic plasticity”: the ease with which synapses - the more than 100 trillion points of contact between nerve cells that determine brain circuitry - are strengthened, weakened, created or destroyed in response to experience. In one recent study, the Shatz group tied two specific members of the MHC1 family, called K and D, to the ability of circuits in a brain region responsible for motor learning to be refined by a learning experience.

This time, the scientists looked at vision processing in the brain. “We’d already found that K and D were located in brain regions we knew mattered: the visual cortex, and a relay station in the brain that sends its input to the visual cortex,” said Shatz.

A good example of the “use it or lose it” manner in which experience-dependent circuit tuning shapes the brain is the ability of one eye to take over brain circuits that normally would be used by the other eye.

“Normally, your two eyes share vision-devoted brain circuits 50/50,” Shatz said. “But when kids are born with a congenital cataract, or lose an eye - or in animal models where one eye is blocked - so that the brain’s visual-information-processing machinery is no longer being used evenly by both eyes, the other eye doesn’t just sit there. It takes over the machinery normally reserved for input from the other eye.”

In order to map the roles of K and D in visual development, Shatz’s group studied mice genetically engineered to lack these two molecules. They found that developmental circuit tuning was abnormal, she said. “The nerve input from the eyes was the same at the gross level - the major nerve tracts still went from the eye to the first visual relay system, and from there to the visual cortex. But the detailed connections within each structure had been altered. The adult patterning didn’t develop normally.”

In these K- and D-deficient mice, the capacity of a more-used eye to dominate visual information-processing circuitry is abnormal, and in a surprising way, said Shatz. “There’s too much of it,” she said. “If one eye stops functioning, the other eye takes over more than its fair share of the cortical machinery devoted to the brain’s visual-information-processing territory.”

In a test of visual performance, Shatz’s team showed that the K- and D-deficient mice could see better through their remaining eye than could ordinary mice raised with a similarly blocked eye. “This suggests there’s some kind of molecular brake on plasticity in the brain, and these molecules are involved in the braking system. Taking off the brake improved performance,” she said.

Using a new method for localizing molecules in three-dimensional chunks of tissue (pioneered by co-author Stephen Smith, PhD, professor of molecular and cellular physiology and a member of the Stanford Cancer Center), Shatz’s team was able to show that K and D are located at synapses. “We’ve placed them at the scene of the crime, right where circuit change happens,” she said. “We think that in the brain they’re pieces of a common braking-system pathway.”

What’s going on in the brain that needs a brake in the first place? Without both accelerators and brakes, any dynamic system - such as the brain, where connections change dramatically in response to whether they’re being used - would become unstable, Shatz said. “Some of us think epilepsy, for example, could be a consequence of this process being not carefully controlled and regulated, and happening too easily.”

That MHC molecules are also expressed on neurons has very large implications, because inflammation works through the immune system. Inflammation triggers the release of molecules called cytokines that change MHC1 levels on cells throughout the body, said Shatz. “If this process also changes MCH1 levels on cells in the brain, could that alter the circuit-tuning process enough to make a difference in behavior?”

There are also therapeutic implications, Shatz observed. “Maybe in children with learning disabilities, the brake’s been applied too hard - or it could mean that after injury to an adult’s brain, taking the brake off or loosening it up a bit could allow the brain to get retrained more easily.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Thursday, November 26, 2015
How Cell Growth Triggers Cell Division
Researchers in Jan Skotheim's lab have discovered a previously unknown mechanism that controls how large cells grow, an insight that could one day provide insight into attacking diseases such as cancer.
Wednesday, October 07, 2015
Delivering Missing Protein Heals Damaged Hearts in Animals
Researchers have discovered that a particular protein, Fstl1, plays a key role in regenerating dead heart-muscle cells.
Tuesday, September 22, 2015
Key Mechanism in Gene Expression Discovered
RNA polymerase II makes life possible by expressing genes. Now, a team of Stanford biologists, chemists and applied physicists has observed it at work in real time.
Thursday, September 17, 2015
X-ray Laser Experiment Could Help in Designing Drugs for Brain Disorders
Scientists found that when two protein structures in the brain join up, they act as an amplifier for a slight increase in calcium concentration, triggering a gunshot-like release of neurotransmitters from one neuron to another.
Monday, August 24, 2015
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
Thursday, July 30, 2015
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Monday, July 27, 2015
A Protein's Novel Role In Several Types Of Cancers Discovered
Stanford ChEM-H scientists are helping to develop a novel cancer therapy based on a new finding of a protein that inadvertently promotes cancer growth.
Friday, February 27, 2015
Stanford Chemists Take Step Toward Solving Mystery of How Enzymes Work
Steven Boxer and his students have found that the electrostatic field within an enzyme accounts for the lion's share of its success.
Wednesday, December 24, 2014
Protein Complex May Play Role in Preventing Many Forms of Cancer, Study Shows
Researchers at the Stanford University School of Medicine have identified a group of proteins that are mutated in about one-fifth of all human cancers.
Tuesday, May 07, 2013
Sequential Genomic Analysis Links Gene with Human Kidney Aging
The new approach that combines sequential transcriptional profiling and eQTL mapping, can help find other genetic associations.
Tuesday, October 27, 2009
Stanford Researchers Find Protein Targets for Potential Treatment of Multiple Sclerosis
Stanford researchers have identified therapy targets that could lead to personalized treatments for MS patients at each phase of the illness.
Monday, February 18, 2008
Scientific News
A Cellular Symphony Responsible for Autoimmune Disease
Broad Institute researchers have used a novel approach to increase our understanding of the immune system as a whole.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Gut Microbes Signal to the Brain When They're Full
Don't have room for dessert? The bacteria in your gut may be telling you something.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos