98-066 (Neural Development)
Brown University News Bureau

The Brown University News Bureau

Distributed February 8, 1999
Contact: Scott Turner

Use them and lose them
Research shows wrong activity worse than no activity in developing brain
New research reported in the Jan. 28 issue of Nature provides insights into a fundamental part of normal brain development. The wrong kind of sensory stimulation is worse than no stimulation at all.

PROVIDENCE, R.I. -- As brain development goes, "bad" or "inappropriate" experiences are worse than no experiences at all, according to a study in the Jan. 28, 1999, issue of Nature. The study shows that the loss of connections between neurons in the brain is not the result of inactivity, as previously thought, but a consequence of activity that is inappropriate.

Experiences during early postnatal life sculpt the connections between neurons in the brain. Some connections, initially formed early in fetal development, are retained and made stronger, while others are weakened and eventually lost. This refinement of connections is responsible for the acquisition of brain function during infancy. While the mechanisms of experience-dependent brain modification normally are responsible for the improvement of function during development, in some clinical conditions they can actually lead to a loss of function.

For example, a loss of function during infant development can result when one eye is deprived of normal visual experience, as can occur with a cataract. As a consequence of this deprivation, connections serving the eye in the brain are weakened to the point that the eye becomes blind. The blindness is a result of a change in the brain, so it persists even when the cataract is removed.

For some time, the weakening between connections in the brain following "one eye" deprivation was considered a consequence of inactivity in the eye. In fact, the eye remains active even with the eyelids closed. The difference between the open and closed eye is the pattern of activity. The activity generated by a seeing eye is like the signals of a well-tuned radio station. The activity generated by an eye with a cataract, or with the lids closed, is more like static.

Researchers in the Howard Hughes Medical Institute and Department of Neuroscience at Brown University tested the validity of a theory developed by Nobel Laureate Leon Cooper and associates at Brown. The theory suggested "static" in the deprived eye actually caused connections to become weaker.

Graduate student Cindi Rittenhouse and professors Harel Shouval, Michael Paradiso and Mark Bear tested that theory in a group of test animals. Half of the animals received a drug that blocked all electrical activity in one eye; the other half simply had their eyelids closed.

In line with the theory, but in contrast to the conventional view, the researchers found that the weakening between connections caused by eyelid closure was far more severe than the weakening caused by blocking all activity in the deprived eye. The finding suggests that it might be possible to "freeze" connections in the brain by blocking activity.

"This result is counterintuitive. You would expect that complete absence of activity would be most severe," said Bear. "This static appears to help drive changes in the same process used to sculpt connections.

"It is important to understand the mechanism by which connections are weakened - not only because such understanding may yield insight into ways that at least one type of blindness can be avoided, but also because this is a fundamental part of normal brain development."

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