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Christine Gall and Gary Lynch found that fragile X model mice trained in three short, repetitious episodes spaced one hour apart performed as well on memory tests as normal mice. Chris Nugent / UC Irvine 

Multiple, short learning sessions strengthen memory formation in fragile X syndrome

A learning technique that maximizes the brain’s ability to make and store memories may help overcome cognitive issues seen in fragile X syndrome, a leading form of intellectual disability, according to UC Irvine neurobiologists.

Irvine, Calif., Dec. 9, 2014 — A learning technique that maximizes the brain’s ability to make and store memories may help overcome cognitive issues seen in fragile X syndrome, a leading form of intellectual disability, according to UC Irvine neurobiologists.

Christine Gall, Gary Lynch and colleagues found that fragile X model mice trained in three short, repetitious episodes spaced one hour apart performed as well on memory tests as normal mice. These same fragile X rodents performed poorly on memory tests when trained in a single, prolonged session – which is a standard K-12 educational practice in the U.S.

“These results are dramatic and never seen before. Fragile X model mice trained using this method had memory scores equal to those of control animals,” said Gall, professor of anatomy & neurobiology and neurobiology & behavior. “Our findings suggest an easily implemented, noninvasive strategy for treating an important component of the cognitive problems found in patients with fragile X syndrome.”

Fragile X syndrome is an inherited genetic condition that causes intellectual and developmental disabilities and is commonly associated with autism. Symptoms include difficulty learning new skills or information.

It’s been known since classic 19th century educational psychology studies that people learn better when using multiple, short training episodes rather than one extended session.

Two years ago, the Lynch and Gall labs found out why. They discovered a biological mechanism that contributes to the enhancing effect of spaced training: Brain synapses – which are the connection points among neurons that transfer signals – encode memories in the hippocampus much better when activated briefly at one-hour intervals.

The researchers found that synapses have either low or high thresholds for learning-related modifications and that the high-threshold group requires hourlong delays between activation in order to store new information.

“This explains why prolonged ‘cramming’ is inefficient – only one set of synapses is being engaged,” said Lynch, professor of psychiatry & human behavior and anatomy & neurobiology. “Repeated short training sessions, spaced in time, engage multiple sets of synapses. It’s as if your brain is working at full power.”

The finding was significant, Gall added, because it demonstrated that a ubiquitous and fundamental feature of psychology can, at least in part, be explained by neurobiology.

It also gave the researchers time-sequencing rules for optimizing forms of learning dependent upon the hippocampus – utilized in the current study. Results appear in the Nov. 25 issue of Proceedings of the National Academy of Sciences.

The UCI scientists stress that the new brain-based training protocols, if applied during childhood, have the potential to offset many aspects of fragile X-related autism. “We believe that synaptic memory mechanisms are used during postnatal development to build functional brain circuits for dealing with confusing environments and social interactions,” Lynch said. “Implementing the brain-based rules during childhood training could result in lifelong benefits for patients.”

He and Gall look forward to collaborating with UCI’s Center for Autism Research & Translation to further evaluate the effect of multiple, short training episodes on learning in fragile X children.

Ronald Seese led the study as part of his work toward a Ph.D. and was assisted by Kathleen Wang and Yue Qin Yao. The research was funded by the National Science Foundation (grant 1146708), the National Institutes of Health (grants MH082042 and NS04260), and the William & Nancy Thompson Family Foundation, via UCI’s Center for Autism Research & Translation.

Media contact: Tom Vasich, Writer – tmvasich@uci.edu

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Located in one of the world’s safest and most economically vibrant communities, it’s Orange County’s second-largest employer, contributing $4.8 billion annually to the local economy.

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