Researchers Identify Enzyme That May Turn Fleeting Experience Into Lasting Memory

"One of the hallmarks of memories that last very long is a close association with emotion," Hegde said in an interview. Hegde and colleagues studied female mice, which, with only one exposure at mating, can later recognize their partner's scent. After mating, a female mouse exposed to the scent of a strange male will not continue her pregnancy. But a female exposed to her partner's scent even a month after mating will continue her pregnancy. This suggests that the female somehow memorized her partner's scent during the process of mating.

"The good thing about this model," Hegde said, "is that it's simple and robust. The memory is unambiguous, and it forms after just one event." In Hegde's model, formation of the lasting memory in the female mouse requires that olfactory (smell) information about her partner coincide with sensory information about the mating. The information is carried by separate pathways, one involving the neurotransmitter glutamate, the other norepinephrine.

Norepinephrine, which is closely related to adrenaline, is a chemical released in the brain during emotional or exciting situations. If it does play a role in humans' being able to vividly remember details of an experience from decades ago--where people were when they heard news of President Kennedy's assassination, for example--the question for researches is how.

"There is a threshold for memory storage," Hegde said. "The brain has to decide what is important for long-term storage. We're trying to understand how norepinephrine leads to strong-memory formation."

When a memory is formed, structural changes take place at synapses, the connections between nerve cells. Proteins synthesized by genes in the nerve cells cause these changes. Generally speaking, the stronger the connections among synapses, the more lasting the memory. Hegde and his colleagues--Jian Mu, M.D., Dwayne W. Godwin, Ph.D., and Chenghai Dong, M.D., Ph.D., all of the Department of Neurobiology and Anatomy--collected data from the mouse brain to suggest how norepinephrine serves as a "gatekeeper" to allow memories to form under certain circumstances.

Their research suggests that the enzyme protein kinase C plays a fundamental role in turning the female's experience of mating into a long-term memory of her partner's scent. Protein kinase C activates genes to express certain proteins. How protein kinase C is linked to gene expression in nerve cells is the subject of a related study by Cristian Skinner, a graduate student in the Hegde lab.

"We've known for a long time that you need gene expression to launch protein synthesis, which is necessary to change the synaptic connections that underlie memory," Hegde said. "This could help look at how genes work to form new connections among synapses."

In collaboration with Josyf Mychaleckyj, D.Phil., of the Wake Forest Center for Human Genomics, Hegde said, the human and mouse genomes--both of which have been completely sequenced--are systematically being searched discover genes that have a critical role in long-term memory. Also, Hegde and his assistant, Thuy Smith, are using gene chips that can screen thousands of genes at the same time to identify the "memory" genes in mice.

"The details might be different in mice and people," Hegde said, "but we think the mechanism will be the same."