Eric Kandel

Infobox Scientist
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name = Eric Richard Kandel

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caption = Kandel at Lange Nacht der Wissenschaften (Long Night of Science) in Austria in 2006
birth_date = birth date and age|1929|11|07|df=yes
birth_place = Vienna, Austria
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fields = psychiatrist and neuroscientist
workplaces = Columbia University College of Physicians and Surgeons
alma_mater = New York University Medical School
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known_for = physiology of memory
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awards = Nobel Prize in Physiology or Medicine 2000
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Eric Richard Kandel (born November 7, 1929) is a psychiatrist, a neuroscientist and professor of biochemistry and biophysics at the Columbia University College of Physicians and Surgeons. He 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 fellow recipients Arvid Carlsson and Paul Greengard. His other honors include the National Medal of Science, the Wolf Prize, the Gairdner Foundation International Award, the Charles A. Dana Award and the Lasker Award. Kandel has been at Columbia University since 1974, and lives in New York City. Kandel has recently 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.

Early years

Kandel was born in 1929 in Vienna, Austria, in a middle-class Jewish family. His mother had come from Kolomyya (Western Ukraine). In that times Kolomyja was in Eastern Poland (he used to joke "as with all bright people, my roots are in Poland") and his father from Olesko in Western Ukraine. His parents met in Vienna and married in 1923, shortly after Hermann Kandel, Eric's father, had established a toy store. They were a thoroughly assimilated and accultured family, which had to leave Austria after the country had been invaded and annexed by Germany in March 1938, Aryanization (Arisierung) started and attacks on Jews and Jewish property escalated. Eventually, when Eric was 9, he and his brother Ludwig, 14, boarded on the Gerolstein from Antwerp in Belgium and joined their uncle in Brooklyn on May, 11 1939. Later his parents succeeded in moving to the US.

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. [ [http://nobelprize.org/nobel_prizes/medicine/laureates/2000/kandel-autobio.html Eric R. Kandel: The Nobel Prize in Physiology or Medicine 2000] , Nobel Foundation. Accessed September 20, 2007. "My grandfather and I liked each other a great deal, and he readily convinced me that he should tutor me in Hebrew during the summer of 1939 so that I might be eligible for a scholarship at the Yeshiva of Flatbush, an excellent Hebrew parochial school that offered both secular and religious studies at a very high level. With his tutelage I entered the Yeshiva in the fall of 1939. By the time I graduated in 1944 I spoke Hebrew almost as well as English, had read through the five books of Moses, the books of Kings, the Prophets and the Judges in Hebrew, and also learned a smattering of the Talmud.... In 1944, when I graduated from the Yeshiva of Flatbush elementary school, it did not as yet have a high school. I went instead to Erasmus Hall High School, a local public high school in Brooklyn that was then academically very strong."]

Kandel's initial intellectual interests lay in the area of history, and that 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 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 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. [ [http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12526779 Activity-dependent presynaptic facilitation and hebbian LTP are both required and interact during classical conditioning in Aplysia] Neuron. 2003 Jan 9;37(1):135-47]

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. [PMID 15967982, PMID 9114065, PMID 7568030] 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. [PMID 8942955, PMID 16134023]

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.

When Kandel won the Nobel Prize in 2000, he "stuck it to the Austrians" by saying it was "certainly not an Austrian Nobel, it was a Jewish-American Nobel." After that, he got a call from then Austrian president Thomas Klestil asking him, "How can we make things right?" Kandel said that first, Doktor-Karl-Lueger-Ring should be renamed. Karl Lueger was an anti-Semitic mayor of Vienna, cited by Hitler in Mein Kampf. Second, he wanted the Jewish intellectual community to be brought back to Vienna, with scholarships for Jewish students and researchers. [Science, 6 June 2008, 320:1269]

References

ources

Kandel, ER (2007): "In Search of Memory - The Emergence of a New Science of Mind." WW Norton & Company, New York.

External links

* [http://www.dradio.de/dkultur/sendungen/kulturinterview/506653/ Interview with Kandel June 2006 in German]
* [http://neuroscience.columbia.edu/department/index.php?ID=27&bio=97 Eric Kandel's Columbia University website]
* [http://www.nobel.se/medicine/laureates/2000/kandel-autobio.html Autobiography at the Nobel Prize website]
* Science Friday: October 13 2000 [http://www.npr.org/dmg/dmg.php?prgCode=TOTN&showDate=02-Jul-2004&segNum=4 NPR interview]
* [http://www.mcmanweb.com/kandel.htm Eric Kandel - A Nobel's Life]
* [http://www.patentgenius.com/inventor/KandelEricR.html Eric R. Kandel's United States Patents]