The Machinery of Memory

How do we learn? How do we recall something that happened many years ago? Over the years, neuroscience researchers have risen to the fundamental challenge posed by these questions.

Using sensitive dyes, researchers track how learning strengthens cellular communication in Aplysia nerve cells. Reds and yellows indicate sites of increased cellular activity, showing one way in which learning physically changes the brain.

Courtesy, with permission: K. Ressner, et al.; The Journal of Neuroscience 2010, 30(26): 8797-8806

Because their nervous systems are much simpler than mammals, Aplysia have become an animal model of choice for many researchers studying some aspects of learning and memory.

Courtesy, with permission: Thomas Carew, University of California, Irvine.

To study how learning and memory happen in people, brain researchers, including SfN Past President Thomas J. Carew, turned to “simpler” organisms, particularly the marine snail Aplysia californica. Carew’s mentor Eric Kandel pioneered the study of memory in Aplysia and produced an extensive body of research on the machinery of memory that earned him a Nobel Prize in 2000.

Snail School

Because of its complexity, making sense of even simple functions in the human brain is extremely difficult. Humans have 100 billion nerve cells, and each one connects with 1,000 to 10,000 others. With just 20,000 nerve cells — a relatively simple nervous system — the Aplysia has become an animal model of choice for many researchers studying learning and memory.

Although they may never learn to spell or multiply fractions, Aplysia do learn from experiences in their environment. In the same way that humans quickly withdraw their hands if they touch a hot stove, Aplysia withdraw two of their sensitive appendages — the siphon and the gill, which are both involved in respiration — when touched. Many researchers have shown that Aplysia can learn to modify this defensive reflex in response to outside information.

For example, like people who stop believing “The Boy Who Cried Wolf,” Aplysia show reduced responses to touch after they are repeatedly touched, a form of learning called habituation. In contrast, an unpleasant mild shock increases their response to a gentle touch — known as sensitization.

With their simplified model of learning in place, scientists have meticulously mapped the connections of nerve cells that control gill and siphon withdrawal. They found this network of neurons to be similar in every Aplysia, which allowed them to return to the study of the exact same set of neurons time after time, and examine how those neurons changed as a function of the animal’s experience.

Memory Molecules

How does a form of learning like sensitization affect the network of cells? Researchers have found it increased the chemical communication between nerve cells, strengthening their connections. Later, research in mammals showed that over time, learning also builds and strengthens the connections between the cells. Forming new memories therefore literally changes the brain, altering the traffic-flow of information.

Carew and his colleagues drilled down even further to find the chemicals in brain cells that make this synaptic strengthening possible. They found learning activated proteins called kinases. Kinases turn other proteins on or off by adding a phosphate chemical group to them — a process called phosphorylation. Turning one kinase on can activate many proteins at once, setting into motion a cascade of events in the cell. Some kinases phosphorylate the proteins that allow chemical signals to influence brain cells — thus learning can alter the very channels of brain communication. By modifying many cellular targets, including these important channels, kinases help form the cellular basis of memory.

There are hundreds of types of kinases that do lots of work for the cell. Carew’s laboratory has identified some of the key players in memory — the kinases that modify the flow of information between brain cells.

Based on these findings, other researchers recently found that turning certain kinases on or off can modify memories in rats. If the same holds true in humans, it may suggest a new type of treatment for posttraumatic stress disorder, in which traumatic experiences can be vividly and repeatedly replayed. In addition, the ability to modify memory might reduce relapse in drug addicts who are vulnerable to exposure to anything they previously associated with drug use.

The basic science discoveries that began with the sea slug have revolutionized what we know about how people learn. These same findings have had extraordinary reach within the neuroscience field, affecting how we think about a wide range of topics, from drug abuse to education.

About the Author

Debra Speert, PhD

Debra is the former director of public information and outreach at the Society for Neuroscience and oversaw content production for BrainFacts.org. While completing a PhD and postdoctoral fellowship in neuroscience, she discovered a knack for explaining tough scientific concepts to general audiences.