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Kandel at Lange Nacht der Wissenschaften (Long Night of Science) in Austria in 2006

 

 

 

Born November 7, 1929 to Present
Vienna, Austria
Fields psychiatrist and neuroscientist
Institutions Columbia University College
of Physicians and Surgeons
Alma mater New York University Medical School
Harvard University
Known for physiology of memory
Notable awards Nobel Prize in Physiology or Medicine 2000

Life is Learning (and a good sense of humor) – A Genius Checks Out the iPad

 

 

 

Eric Richard Kandel (born November 7, 1929) is an American neuropsychiatrist who was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons. He shared the prize with Arvid Carlsson and Paul Greengard.

Kandel is professor of biochemistry and biophysics at the Columbia University College of Physicians and Surgeons and a Senior Investigator in the Howard Hughes Medical Institute. He was also the founding director of the Center for Neurobiology and Behavior, which is now the Department of Neuroscience at Columbia. Kandel authored In Search of Memory: The Emergence of a New Science of Mind (WW Norton), which chronicles his life and research. The book was awarded the 2006 Los Angeles Times Book Award for Science and Technology.

Kandel was born in 1929 in Vienna, Austria, in a middle-class Jewish family. His mother, Charlotte Zimels, was born in 1897 in Kolomyya, Pokuttya (modern Ukraine), and came from a well-educated middle-class family. At that time Kolomyya was in Eastern Poland (he used to joke “as with all bright people, my roots are in Poland.” His father was born in 1898 into a poor family in Olesko, Galicia (then part of Austria-Hungary). At the beginning of World War I his parents moved to Vienna where they met and married in 1923, shortly after Hermann Kandel, Eric’s father, had established a toy store. They were a thoroughly assimilated and acculturated family, who had to leave Austria after the country had been annexed by Germany in March 1938. Aryanization (Arisierung) started; attacks on Jews escalated; Jewish property was confiscated. Eventually, when Eric was 9, he and his brother Ludwig, 14, boarded the “Gerolstein” at Antwerp in Belgium and joined their uncle in Brooklyn on May 11, 1939. Later his parents succeeded in moving to the US.

When Kandel won the Nobel Prize in 2000, it was claimed in Vienna that he was an “Austrian” Nobel, something he found “typically Viennese: very opportunistic, very disingenuous, somewhat hypocritical.” Afterwards, he received a letter from Austria’s President Klestil asking, `”How can we recognize you?” Kandel then proposed to have a symposium on the response of Austria to National Socialism.[1])

After arriving in the United States, and settling in Brooklyn, Kandel was tutored by his grandfather in Judaic studies, and was accepted at the Yeshivah of Flatbush, graduating in 1944. He attended Brooklyn’s Erasmus Hall High School, a Public high school.

Kandel’s initial intellectual interests lay in the area of history. (History and Literature was his undergraduate major at Harvard University.) He wrote an honors dissertation on “The Attitude Toward National Socialism of Three German Writers: Carl Zuckmayer, Hans Carossa, and Ernst Jünger.” While at Harvard, a place dominated by the work of B. F. Skinner, Kandel became interested in learning and memory. It should be noted, however, that while Skinner championed a strict separation of psychology, as its own level of discourse, from biological considerations such as neurology, Kandel’s work is essentially centered on an explication of the relationships between psychology and neurology.

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

Medical school and early research

In 1952 he started at the New York University 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 Beecher Scoville and Brenda Milner had recently described the patient HM, who had lost explicit memory storage following removal of the hippocampus. 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 of 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 residency in psychiatry, Kandel went to Paris to learn about the marine mollusc Aplysia californica 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 form of pre-synaptic potentiation that seemed to correspond to a simple form of learning.

Faculty member at New York University Medical School

 

Kandel in 1978

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.”

Molecular changes during learning

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 (cAMP) 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 cAMP 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 (PKA) acted in this biochemical pathway in response to elevated levels of cAMP. Steven Siegelbaum identified a potassium channel that could be regulated by PKA, coupling serotonin’s effects to altered synaptic electrophysiology.

In 1983 Kandel helped form the 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 PKA 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.

Experimental support for Hebbian learning

Some of the synaptic changes observed by Kandel’s laboratory provide examples of Hebbian learning. One article describes the role of Hebbian learning in the Aplysia siphon-withdrawal reflex.

The Kandel lab has also performed important experiments using transgenic mice as a system for investigating 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. His 2006 autobiographical book, “In Search of Memory: The Emergence of a New Science of Mind,” is a popularized account of his life and career.

Continuing work at Columbia University

Kandel actively contributes to science as a member of the Division of Neurobiology and Behavior at the Department of Psychiatry at Columbia University. In 2008, he and Daniela Pollak discovered that conditioning mice to associate a specific noise with protection from harm, a behavior called “learned safety,” produced a behavioral antidepressant effect comparable to medications. This finding, reported in Neuron, may inform further studies of the cellular interactions between antidepressants and behavioral treatments. Kandel has been at Columbia University since 1974, and lives in New York City.

Awards

He is a member of the prize committee for neuroscience of Kavli Prize.

 

 

 

Videos On Memory with Eric Kandel MD

Sunrise in Austin, Texas

Credit: lkw51 – May 2011