A change of mind: One protein appears to control neurons' ability to react to new experiences

Mar 24, 2010 by Anne Trafton
MIT neuroscientists have shown that the protein Arc is necessary for neurons like this one to adjust their responses to new sensory stimuli. (The blue circle is the neuron’s nucleus, and the red strands are actin filaments.) Image: Jason Shepherd

(PhysOrg.com) -- Plasticity -- the brain's ability to change in response to external input -- is critical for most cognitive functions, including learning and memory. Those changes usually involve a strengthening or weakening of synapses, the connections between brain cells (neurons).

MIT neuroscientists have now found that a single protein, known as Arc, appears to control neurons’ ability to strengthen and weaken their synapses by regulating the number of neurotransmitter receptors on their surfaces. The finding could help researchers identify new drug targets for Fragile X and Angelman syndromes — inherited forms of mental retardation that have been linked to deficits of Arc.

“The more we understand the chain of cellular events that Arc is involved in, the more we can identify particular targets where we could intervene,” says Mriganka Sur, head of MIT’s Department of Brain and Cognitive Sciences (BCS).

Sur and Mark Bear, the Picower Professor of Neuroscience, are senior authors of a paper on the work that appeared in the March 14 online edition of .

A surprising discovery

Jason Shepherd, co-lead author of the paper and a postdoctoral associate in Bear’s lab, began studying Arc as a grad student at Johns Hopkins University. He and his colleagues showed that Arc weakens synapses by removing receptors for glutamate, a neurotransmitter that stimulates , from neuron cell membranes. They also discovered that when the Arc gene is turned off in mice, they lose their ability to form long-term memories.

In the new study, Shepherd and co-lead author Cortina McCurry, a recent PhD recipient in BCS, did a series of experiments designed to pinpoint the role of Arc in the visual cortex of mice. They started with a classic experimental setup that involves sealing one eye for two days, depriving the eye of . In normal mice, this strengthens synapses in the part of the cortex receiving input from the open eye, and weakens them in cortical cells wired to the closed eye.

Shepherd and McCurry performed their experiments on mice with a mutation in the Arc gene that renders the protein ineffective. Because of Arc’s known role in weakening synapses, they expected mice without Arc not to show any synaptic weakening from the closed eye. That prediction came true, but to the researchers’ surprise, they found that the synaptic strengthening normally seen from the open eye also disappeared.

“If you knock out the gene, you don’t get either response,” says Shepherd. “The brain is not responsive at all to the changes in sensory input.”

They observed the same lack of plasticity in studies of Arc-deficient mice that were repeatedly exposed to the same visual stimulus (for example, a horizontal bar), which normally provokes neurons to enhance their response to that particular stimulus.

The results suggest that Arc has an indirect role in inserting glutamate receptors in the cell membrane, as well as its previously known role in removing them, according to the researchers. “It’s remarkable to find one single gene and its protein to be so responsible” in different types of plasticity, says Sur.

While others have shown in experiments with neurons that Arc appears to have a role in both suppressing and stimulating synapses, this paper is the first to demonstrate the effect in living animals, says Hey-Kyoung Lee, associate professor of biology at the University of Maryland, who was not involved in the research. “The current paper clearly shows that Arc plays a critical role in shaping cortical synapses with sensory experience,” she says.

Shepherd is now planning experiments to image the Arc protein in single cells in the . He also plans to further investigate the protein’s role in Fragile X and Angelman syndromes.

Explore further: New mapping approach lets scientists zoom in and out as the brain processes sound

More information: Paper: www.nature.com/neuro/journal/v… ent/abs/nn.2508.html

Related Stories

Back to (brain) basics

Nov 03, 2009

(PhysOrg.com) -- In his own words, MIT neuroscientist Mark Bear admits he did not "wake up one day and say 'Hey, I'm going to cure autism.'" But, after decades of painstaking basic research on how the brain ...

Researchers Discover How Brain Protein Might Control Memory

Nov 11, 2006

Researchers at Johns Hopkins have figured out how one particular protein contributes to long-term memory and helps the brain remember things longer than an hour or two. The findings are reported in two papers in the Nov. ...

Loss of enzyme reduces neural activity in Angelman syndrome

Mar 04, 2010

Angelman Syndrome is a rare but serious genetic disorder that causes a constellation of developmental problems in affected children, including mental retardation, lack of speech, and in some cases, autism. Over a decade ago, ...

Team IDs binocular vision gene

Sep 14, 2007

In work that could lead to new treatments for sensory disorders in which people experience the strange phenomena of seeing better with one eye covered, MIT researchers report that they have identified the gene responsible ...

Study suggests caution on a new anti-obesity drug in children

May 07, 2008

A new class of anti-obesity drugs that suppresses appetite by blocking cannabinoid receptors in the brain could also suppress the adaptive rewiring of the brain necessary for neural development in children, studies with mice ...

Recommended for you

Steering the filaments of the developing brain

10 hours ago

During brain development, nerve fibers grow and extend to form brain circuits. This growth is guided by molecular cues (Fig. 1), but exactly how these cues guide axon extension has been unclear. Takuro Tojima ...

Do we really only use 10% of our brain?

11 hours ago

As the new film Lucy, starring Scarlett Johansson and Morgan Freeman is set to be released in the cinemas this week, I feel I should attempt to dispel the unfounded premise of the film – that we only use 10% of our brains ...

Birthday matters for wiring-up the brain's vision centers

Jul 31, 2014

Researchers at the University of California, San Diego School of Medicine have evidence suggesting that neurons in the developing brains of mice are guided by a simple but elegant birth order rule that allows them to find ...

User comments : 0