A protein known primarily for its role in killing cells also plays a part in memory formation, researchers in Urbana-Champaign report. Their work exploring how zebra finches learn songs could have implications for treatment of neurodegenerative conditions such as dementia and Alzheimer's disease.
When activated, the enzyme caspase-3 triggers a synaptic process essential for memory storage, according to Graham R. Huesmann, PhD'05 , MD'07, and David F. Clayton, PhD, professor of cell and developmental biology at the U of I Beckman Institute for Advanced Science and Technology. Their article, which appeared 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 postsynaptic 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 usually is 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, 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 received a medical degree in May.
"Graham had this intuition that growth and memory are really a kind of remodeling," says Clayton. "You can';t have growth without death."