By probing the synaptic connections between nerve cells in the humble sea slug, Eric Kandel has uncovered some of the basic molecular mechanisms underlying learning and memory in animals ranging from snails to flies to mice and even in…
By probing the synaptic connections between nerve cells in the humble sea slug, Eric Kandel has uncovered some of the basic molecular mechanisms underlying learning and memory in animals ranging from snails to flies to mice and even in humans. His groundbreaking studies have demonstrated the fundamental ways that nerve cells alter their response to chemical signals to produce coordinated changes in behavior. This work is central to understanding not only normal memory but also dementia and other mental illnesses that affect memory. Kandel's research has shown that learning produces changes in behavior by modifying the strength of connections between nerve cells, rather than by altering the brain's basic circuitry. He went on to determine the biochemical changes that accompany memory formation, showing that short-term memory involves a functional modulation of the synapses while long-term memory requires the activation of genes and the synthesis of proteins to grow new synaptic connections. For this work, the Austrian-born Kandel was awarded the 2000 Nobel Prize in Physiology or Medicine. The traumatic events of Kandel's childhood likely influenced his later interest in the biological mechanisms of memory. He was only eight when, in 1938, Nazi Germany annexed his homeland, but the humiliation and discrimination that Kandel, his family, and other Jews suffered under this oppressive regime were forever seared into his memory. In 1939, on the eve of World War II, his family fled Austria for the United States. As a college student at Harvard, Kandel majored in history and literature, but he was drawn to psychoanalysis after befriending a native Austrian student whose parents were prominent psychoanalysts in Sigmund Freud's circle. Kandel went to medical school at New York University with the goal of studying psychiatry and becoming a psychoanalyst himself. But thinking that he should know more about how the brain works, he took a neurophysiology course that shifted his interest toward research into the biology of memory. "The cell and molecular mechanisms of learning and memory struck me as a wonderful problem to study … It was clear to me even then that learning and memory were central to behavior, and thus to psychopathology and to psychotherapy," Kandel recalled. Initially, he focused on recording the activity of nerve cells in the hippocampus, a region of the brain vital to memory formation. The mammalian hippocampus, however, with its seemingly infinite number of neurons and synaptic connections, made it difficult to study learning and memory at the cellular level. Kandel soon realized he needed a simpler system and chose the invertebrate sea slug Aplysia, much to the dismay of his colleagues who thought that no self-respecting neurophysiologist would abandon the study of learning in mammals to work on an invertebrate. This bold decision paid off, though, and Kandel now works to instill in his students a sense that risk-taking is important to good science. "I try to convey to students my love of science and my conviction that exploring the biology of the brain is an unmatched scientific adventure," he explained. "I also encourage them to think boldly and to work carefully; to take gambles on their ideas and to try new approaches. I also tell them never to be embarrassed in exposing their ignorance … We are all here to learn, and the learning never ends." More recently, Kandel has expanded his studies of simple learning and memory in Aplysia to include more complex forms of memory storage in genetically modified mice. These studies have focused on explicit memory (the conscious recall of information about places and objects), revealing the importance of a balance of activation and inhibition in memory storage so that animals as well as humans do not store information in their memories that is not important to recall.