Surprised rats and better hearing

Conducting basic scientific research and making new discoveries in a complex field is like creating a single brick and adding it to a wall long under construction. The research of Hebrew University neurobiologist Prof. Israel Nelken, who led a team investigating brain activity in the auditory cortices of rat brains, could in the long term lead to the development of better hearing aids in humans. The findings were published recently in the prestigious journal Neuron.

They spent three years on this study, but in fact began investigating the subject 13 or 14 years ago. “We wanted to know what is and what is not important in hearing, which occurs through the ears but even more in the brain,” said Nelken. Rats, he notes, are very intelligent animals, and their hearing is as good as that of many other mammals. By implanting multiple tiny electrodes in rat auditory cortices, the part of the cortex that responds to sound, the team studied the effects of “surprise sounds” on the rats’ neuronal activity.

Brain activity in single neurons was assessed. “We found that activity of neurons is sensitive to surprise.

A sequence of identical tones creates expectations even in anesthetized mammals, and the responses to rare tones tend to be stronger than responses to common ones,” he said.

“Near my home in Jerusalem is a school for deaf children, and a sign has been posted to warn drivers that deaf children are crossing the road,” says Nelken. “One would expect such a sign outside a school for the blind. But hearing provides important information about events around you, and a deaf child doesn’t hear the noise behind him. Sounds come from all directions, not only ahead where he can see what is happening, so unexpected noise is extremely important.”

People who have normal hearing are more sensitive to slight differences between tones. “We showed that sensitivity to surprising tones is much stronger; the brain learns very quickly and the activity is reduced in response to expected sounds. The mechanisms underlying surprise reactions appear very early in life and are present even in the fetus.”

Nelken, who became a full professor in 2008 and has published about 80 articles in scientific journals, says that rats are smarter, more aggressive and have more interesting behavior than mice. But similar phenomena have been tested elsewhere in rhesus monkeys, mice, gerbils and cats as well as in birds, such as barn owls, he says, suggesting that the underlying mechanisms are very basic to the function of any sensory system.

“Our central question was how the senses work to collect information from the past and learn from it how to function better in the world. Sensitivity to surprise is very important. If a rat has greater ability to predict future events in the world, it will be able to collect more rewards in the form of food, locating a place to live and finding a mate. The more the past can be used to predict future, the easier rewards will be won,” he continues.

The same basic mechanism of repeated sounds may be involved in all kinds of human psychiatric diseases, including schizophrenia. In future research, Nelken and his team hope to “understand the borders of early hearing involving surprise and how this affects behavior.” The research was funded by the Medical Research Fund of Health Ministry’s chief scientist’s office, under the framework of ERANET Neuron.

DOUBLE-JOINTED JOINT PAINT Acrobats who are double jointed amaze with their incredible flexibility, but a prospective study by British researchers has found double-jointed adolescents (doctors use the term joint hypermobility) are at greater risk for developing musculoskeletal pain as they get older, particularly in the shoulders, knees, ankles and feet.

Published in the journal Arthritis & Rheumatism,the findings suggest that children with joint hypermobility are almost twice as likely to develop pain at these joints.

When ligaments are loose (ligamentous laxity), this may cause joints to extend beyond the normal range (hypermobility). It is believed that genes may be responsible for the phenomenon. But when genetic causes are not found and joint pain is present, doctors may call it “benign joint hypermobility syndrome.”

Several studies have shown that joint pain is common in children with hypermobility, with some reports as high as 74 percent of those with joint hypermobility experiencing pain. Yet other research suggests that while musculoskeletal pain is a frequent complaint in adolescents, it is no more common in those with joint hypermobility.

“With such conflicting evidence we set out to determine whether adolescents with joint hypermobility are at risk of developing musculoskeletal pain,” explained lead author Prof. Jon Tobias from the University of Bristol. 1,267 boys and 1,634 girls were assessed in the study. Individual joints were determined to be hypermobile if, for example, the knees could be bent backwards or the thumbs could touch the wrist. At nearly age 18, participants were evaluated for joint pain with a questionnaire.

About 5% of participants were hypermobile at age 14, and at age 18, close to 45% of participants reported pain lasting one or more days. Joint hypermobility was associated with approximately a two-fold increased risk of moderately severe pain at the shoulder, knee, ankle and foot. Interestingly, this increased risk was particularly marked in obese participants, with over a 10-fold increased risk of knee pain observed in obese participants with hypermobility, possibly reflecting the role of mechanical factors.

Tobias concluded: “Our study provides the first prospective evidence that adolescents who display joint hypermobility are at increased risk of developing musculoskeletal pain as they get older, particularly in the shoulder, knee, ankle or feet. Further investigation of increased joint pain in teens is warranted to determine if the long-term effects of joint hypermobility puts them at risk for developing osteoarthritis later in life.”