Study shows how insulin-like molecules play critical role in learning and memory

by Peter Reuell
“People think of insulin and diabetes, but many metabolic syndromes are associated with some types of cognitive defects and behavioral disorders, like depression or dementia,” said Yun Zhang, whose new research demonstrates how the signaling pathway of insulin and insulinlike peptides plays a critical role in helping to regulate learning and memory. Credit: Rose Lincoln/Harvard Staff Photographer

Though it's most often associated with disorders like diabetes, Harvard researchers have shown how the signaling pathway of insulin and insulin-like peptides plays another critical role in the body – helping to regulate learning and memory.

In addition to showing that the insulin-like peptides play a critical role in regulating the activity of neurons involved in learning and memory, a team of researchers led by Yun Zhang, Associate Professor of Organismic and , show that the interaction between the molecules can fine-tune how, or even if, learning takes place. Their work is described in a February 6 paper in Neuron.

"People think of insulin and diabetes, but many metabolic syndromes are associated with some types of and behavioral disorders, like depression or ," Zhang said. "That suggests that insulin and insulin-like peptides may play an important role in , but it's been very difficult to nail down the underlying mechanism, because these peptides do not have to function through that connect different in the brain"

To get at that mechanism, Zhang and colleagues turned to an organism whose and nervous system are well described and highly accessible by genetics – C. elegans.

Using , researchers altered the small, transparent worms by removing their ability to create individual insulin-like compounds. These new "mutant" worms were then tested to see whether they would learn to avoid eating a particular type of bacteria that is known to infect the worms. Tests showed that while some worms did learn to steer clear of the bacteria, others didn't – suggesting that removing a specific insulin-like compound halted the worms' ability to learn.

Researchers were surprised to find, however, that it wasn't just removing the molecules that could make the animals lose the ability to learn – some peptide was found to inhibit learning.

"We hadn't predicted that we would find both positive and negative regulators from these peptides," Zhang said. "Why does the animal need this bidirectional regulation of learning? One possibility is that learning depends on context. There are certain things you want to learn – for example, the worms in these experiments wanted to learn that they shouldn't eat this type of infectious bacteria. That's a positive regulation of the learning. But if they needed to eat, even if it is a bad food, to survive, they would need a way to suppress this type of learning."

Even more surprising for Zhang and her colleagues was evidence that the various insulin-like molecules could regulate each other.

"Many animals, including the humans, have multiple insulin-like molecules and it appears that these molecules can act like a network," she said. "Each of them may play a slightly different role in the nervous system, and they function together to coordinate the signaling related to learning and memory. By changing the way the molecules interact, the brain can fine tune learning in a host of different ways."

Going forward, Zhang said she hopes to characterize more of the insulin-like peptides as a way of better understanding how the various molecules interact, and how they act on the neural circuits for .

Understanding how such pathways work could one day help in the development of treatment for a host of cognitive disorders, including dementia.

"The signaling pathways for insulin and insulin-like are highly conserved in mammals, including the humans," Zhang said. "There is even some preliminary evidence that insulin treatment, in some cases, can improve cognitive function. That's one reason we believe that if we understand this mechanism, it will help us better understand how pathways are working in the human brain."

Related Stories

New evidence links Alzheimer's disease and diabetes

Mar 20, 2012

An emerging body of research suggests that Alzheimer's disease may be linked to insulin resistance, constituting a third type of diabetes. This model is based on several observations including an increased risk of developing ...

Preserving memory with age

May 18, 2010

If you lived longer, would you still remember everything? It depends. Two methods of extending life span have very different effects on memory performance and decline with age, researchers at Princeton University have shown ...

Recommended for you

New ALS associated gene identified using innovative strategy

8 hours ago

Using an innovative exome sequencing strategy, a team of international scientists led by John Landers, PhD, at the University of Massachusetts Medical School has shown that TUBA4A, the gene encoding the Tubulin Alpha 4A protein, ...

Can bariatric surgery lead to severe headache?

8 hours ago

Bariatric surgery may be a risk factor for a condition that causes severe headaches, according to a study published in the October 22, 2014, online issue of Neurology, the medical journal of the American Academy of Neurol ...

Bipolar disorder discovery at the nano level

9 hours ago

A nano-sized discovery by Northwestern Medicine scientists helps explain how bipolar disorder affects the brain and could one day lead to new drug therapies to treat the mental illness.

Brain simulation raises questions

12 hours ago

What does it mean to simulate the human brain? Why is it important to do so? And is it even possible to simulate the brain separately from the body it exists in? These questions are discussed in a new paper ...

Human skin cells reprogrammed directly into brain cells

12 hours ago

Scientists have described a way to convert human skin cells directly into a specific type of brain cell affected by Huntington's disease, an ultimately fatal neurodegenerative disorder. Unlike other techniques ...

User comments