Study on how birds learn songs may shed light on brain process

By Jim Barlow

A gene that contributes to Alzheimer's disease also may guide song-learning
in birds, according to research at the UI. The gene contains the
instructions to make a protein called synelfin that is linked with
devastating brain lesions known as senile plaques, a signature of
Alzheimer's.

The research, which is described in the August issue of the journal Neuron,
indicates that the same protein is abundant in zebra finches in the parts
of the brain responsible for song-learning, but then declines as the
learning ceases.

"The amount of the protein appears to be correlated with song-learning
activity," said David Clayton, a molecular biologist in the UI cell and
structural biology department. "This protein may provide a window into a
very basic brain process. Our songbird studies suggest it may have a normal
function to increase learning. Yet as a side effect, it also may make human
brain tissue more susceptible to senile plaques."

Clayton and his colleague, Julia George, discovered the synelfin protein
after setting out to address a longstanding question about the behavior of
birds such as canaries and zebra finches: Why do most songbirds learn their
songs only during a particular time of their lives?

The researchers, whose work is supported by the National Institutes of
Health, theorized that there may be changes in specific proteins within a
key brain region known as lMAN (pronounced el-man). Using recombinant DNA
methods, they made a collection of probes for genes that encode songbird
brain proteins. After analyzing the proteins one by one, the researchers
picked synelfin to study because they found it to be turned on in the lMAN
region of zebra finches that were learning their songs, and then abruptly
turned off. The bird learns its song when it is about a month old by
listening to a tutor - usually its father.

Exactly how the protein works in songbirds, or in humans, is not known.
However, "in humans, the distribution of synelfin is the best predictor yet
of where senile plaques are most likely to develop," Clayton said. "A
normal, healthy brain has few, if any, plaques; the more plaques you have,
the sicker you are."

Synelfin and another protein, the amyloid precursor protein, give rise to
small peptides that make up the sticky, insoluble skeleton of the senile
plaque.

The UI researchers have found at least one other clue potentially linking
synelfin to Alzheimer's disease. Synelfin resembles apolipoproteins,
molecules that mediate protein activity. Last year, other researchers
showed that the apolipoprotein E4, a major carrier of hydrophobic molecules
in the brain, is a significant genetic risk factor for the development of
Alzheimer's.

Clayton speculates that synelfin may be an essential factor in plaque
formation and that it may interact with different apolipoproteins to
influence the likelihood of senile plaques and Alzheimer's.