How Zebra Finches Learn Songs: Cellular Killer Also Important To Memory

When activated, the enzyme caspase-3 triggers a synaptic process essential for memory storage, according to Graham R. Huesmann and David F. Clayton of the department of cell and developmental biology and of the U. of I. Beckman Institute for Advanced Science and Technology. Their article, which appears in the Dec. 21 issue of the journal Neuron, describes their findings, which provide "the first direct evidence of a change in the availability of activated caspase-3 protein in the brain during the process of memory formation."

Caspase-3 is best known for its role in a biochemical cascade that leads to apoptotic cell death. These new findings demonstrate that the enzyme acts differently under different conditions, and suggest that its regulation in the brain is more complex than previously thought. Huesmann and Clayton examined the brains of zebra finches after exposing the birds to tape recordings of the songs of other birds. They found an increase in the concentration of activated caspase-3 in post-synaptic sites of the auditory forebrain shortly after the birds were exposed to unfamiliar bird songs. Exposure to familiar songs caused no significant increase in the enzyme.

The researchers demonstrated that the activated form of caspase-3 is short-lived and highly localized, which may explain why the enzyme does not trigger apoptosis.

They also showed that activated caspase-3 is always present in brain cells, but that it is usually bound by an inhibitor, BIRC4. For a short time after the birds are exposed to novel songs, the inhibitor releases the activated caspase-3. The concentration of unbound, activated caspase-3 peaks about 10 minutes after the birds hear the new songs.

Other research has added to the evidence that caspase-3 is essential to memory formation. Caspase-3 inhibitors injected into rat brains interfere with the animals' spatial memory and active avoidance learning.

Caspase-3's dual role as a cell killer and memory builder has long intrigued Huesmann, the lead author of the study. "Is it Memory or Is It Death? Caspase-3 and Memory Formation," was his dissertation title. Huesmann has a doctorate in neuroscience and is completing a medical degree at Illinois.

"Graham had this intuition that growth and memory is really a kind of remodeling," said Clayton, who is a professor of cell and structural biology. "You can't have growth without death."