Eric R Kandel

Eric R. Kandel is a neuroscientist who has been at Columbia University since 1974. He won a Nobel Prize in the year 2000 for his research on the physical basis of memory storage by neurons.

Eric Kandel was born in Vienna, Austria in 1929 and is among the many American scientists who were driven out of Europe by Nazi Germany. His initial intellectual interests were in the area of history, and that was his undergraduate major at Harvard. He wrote an honors dissertation on "The Attitude Toward National Socialism of Three German Writers: Carl Zuckmayer, Hans Carossa, and Ernst Junger." While at Harvard, a place dominated by the work of B. F. Skinner, Kandel has become interested in learning and memory.

The world of neuroscience was first opened up to Dr. Kandel through his interactions with a college friend whose parents were Freudian phychoanalysts. Freud, a pioneer in revealing the importance of unconscious neural processes, was at the root of Eric Kandel's interest in the biology of motivation and unconscious and conscious memory.

In 1952 he started N.Y.U. Medical School. By graduation he was firmly interested in the biological basis of the mind. During this time he met his future wife, Denise Bystryn. Kandel was first exposed to research in Harry Grundfest's laboratory at Columbia University. Grundfest was known for using the oscilloscope to demonstrate that action potential conduction velocity depends on axon diameter. The researchers Kandel interacted with were contemplating the technically challenging idea of intracellular recordings of the electrical activity of the relatively small neurons of the vertebrate brain.

After starting his neurobiological work in the difficult thicket of the electrophysiology of the cerebral cortex, Kandel was impressed by the progress that had been made by Stephen Kuffler using a much more experimentally accessible system: neurons isolated from marine invertebrates. After becoming aware of Kuffler's work in 1955, Kandel graduated from medical school and learned from Stanley Crain how to make microelectrodes that could be used for intracellular recordings of relatively large crayfish giant axons.

Karl Lashley, a well known American neuropsychologist, had tried but failed to identify an anatomical locus for memory storage in the cortex at the surface of the brain. When Kandel joined the Laboratory of Neurophysiology at the National Institutes of Health in 1957, William Scoville and Brenda Milner had recently described the patient H.M., who had lost explicit memory storage following removal of the hipppocampus. Kandel took on the task of performing electrophysiological recordings of hippocampal pyramidal neurons. Working with Alden Spencer, electrophysiological evidence was found for action potentials in the dendritic trees of hippocampal neurons. They also noticed the spontaneous pace-maker-like activity of these neurons and a robust recurrent inhibition in the hippocampus. With respect to memory, there was nothing in the general electrophysiological properties of hippocampal neurons that suggested why the hippocampus was special for explicit memory storage.

Kandel began to realize that memory storage must rely on modifications in the synaptic[?] connections between neurons and that the complex connectivity of the hippocampus did not provide the best system for study the detailed function of synapses. Kandel was aware that comparative studies of behavior, such as those by Konrad Lorenz, Niko Tinbergen, and Karl von Frisch had revealed conservation of simple forms of learning across all animals. Kandel felt it would be productive to select a simple animal model that would facilitate electrophysiological analysis of the synaptic changes involved in learning and memory storage. He believed that, ultimately, the results would be found to be applicable to humans. This decision was not without risks since many senior biologists and psychologists believed that nothing useful could be learned about human memory by studying invertebrate physiology.

In 1962, after completing his medical residency, Kandel went to Paris to learn about the marine mollusk Aplysia from Ladislav Tauc. Kandel had realized that simple forms of learning such as habituation, sensitization, classical conditioning, and operant conditioning could readily be studied with ganglia isolated from Aplysia. "While recording the behavior of a single cell in a ganglion, one nerve axon pathway to the ganglion could be stimulated weakly electrically as a conditioned [tactile] stimulus, while another pathway was stimulated as an unconditioned [pain] stimulus, following the exact protocol used for classical conditioning with natural stimuli in intact animals." Electrophysiological changes resulting from the combined stimuli could then be traced to specific synapses. In 1965 Kandel published his initial results, including a from of post-synaptic potentiation that seemed to correspond to a simple form of learning.

Kandel took a position in the Departments of Physiology and Psychiatry at the New York University Medical School, eventually forming the Division of Neurobiology and Behavior. Working with Irving Kupferman and Harold Pinsker it was possible to develop protocols for demonstrating simple forms of learning by intact Aplysia. In particular, the now famous gill-withdrawal reflex, by which the tender Aplysia gill tissue is withdrawn from danger, was shown to be sensitive to both habituation and sensitization. By 1971 Tom Carew joined the research group and helped extend the work from studies restricted to short-term memory to additional experiments that included additional physiological processes required for long-term memory.

By 1981, laboratory members including Terry Walters, Tom Abrams, and Robert Hawkins had been able to extend the Aplysia system into the study of classical conditioning, a finding which helped close the apparent gap between the simple forms of learning often associated with invertebrates and more complex types of learning more often recognized in vertebrates. Along with the fundamental behavioral studies, other work in the lab traced the neuronal circuits of sensory neurons, interneurons, and motor neurons involved in the learned behaviors. This allowed analysis of the specific synaptic connections that are modified by learning in the intact animals. The results from Kandel's laboratory provided solid evidence for the mechanistic basis of learning as "a change in the functional effectiveness of previously existing excitatory connections."

Starting in 1966 James Schwartz collaborated with Kandel on a biochemical analysis of changes in neurons associated with learning and memory storage. BY this time it was known that long-term memory, unlike short-term memory, involved the synthesis of new proteins. By 1972 they had evidence that the second messenger molecule cyclic-AMP was produced in Aplysia ganglia under conditions that cause short-term memory formation (sensitization). In 1974 the Kandel lab moved to Columbia University as founding director of the Center for Neurobiology and Behavior. It was soon found that the neurotransmitter serotonin acting to produce the second messenger cyclic-AMP is involved in the molecular basis of sensitization of the gill-withdrawal reflex. By 1980, collaboration with Paul Greengard resulted in demonstration that cAMP-dependent protein kinase acted in this biochemical pathway in response to elevated levels of cyclic-AMP. Steven Siegelbaum identified a potassium channel that could be regulated by the cAMP-dependent protein kinase, coupling serotonin's effects to altered synaptic electrophysiology.

In 1983 Kandel helped form a Howard Hughes Medical Research Institute at Columbia devoted to molecular neural science. The Kandel lab took on the task of identifying proteins that had to be synthesized in order to convert short-term memories into long-lasting memories. One of the nuclear targets for cAMP-dependent protein kinase is the transcriptional control protein CREB (cAMP response element binding protein). In collaboration with David Glanzman and Craig Bailey, CREB was identified as being a protein involved in long-term memory storage. One result of CREB activation is an increase in the number of synaptic connections. Thus, short-term memory had been linked to functional changes in existing synapses, while long-term memory was associated with a change in the number of synaptic connections.

The Kandel lab has also performed important experiments using transgenic mice as a system for investing the molecular basis of memory storage in the vertebrate hippocampus. Kandel's original idea that learning mechanisms would be conserved between all animals has been confirmed. Neurotransmitters, second messenger systems, protein kinases, ion channels, and transcription factors like CREB have been confirmed to function in both vertebrate and invertebrate learning and memory storage.

Kandel is also well known for the textbooks he has helped write such as Principles of Neural Science. Kandel has been a member of the National Academy of Sciences, USA, since 1974.

External Links

• Eric Kandel's Columbia University website (http://cpmcnet.columbia.edu/dept/neurobeh/Kandel)
• Autobiography at the Nobel Prize website (http://www.nobel.se/medicine/laureates/2000/kandel-autobio)