Eric R. Kandel
Encyclopedia
Eric Richard Kandel 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 neuron
s. 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.
, 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
. 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." He also said 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. He also proposed to have a symposium on the response of Austria to National Socialism. Kandel has since accepted an honorary citizenship of Vienna and participates in the academic and cultural life of his native city.
After arriving in the United States, and settling in Brooklyn
, Kandel was tutored by his grandfather in Judaic studies, and was accepted at the Yeshiva 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.
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 neuron
s 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 microelectrode
s 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.
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."
). 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.
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. Neurotransmitter
s, second messenger systems, protein kinase
s, ion channel
s, and transcription factor
s 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
. Published in 2000 by McGraw-Hill Medical, his textbook focuses on how the brain and neurons work. The book contains visuals and is often used in medical schools for neurological research. 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.
.
He is a member of the prize committee for neuroscience of Kavli Prize
.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
neuropsychiatrist
Neuropsychiatry
Neuropsychiatry is the branch of medicine dealing with mental disorders attributable to diseases of the nervous system. It preceded the current disciplines of psychiatry and neurology, in as much as psychiatrists and neurologists had a common training....
who was a recipient of the 2000 Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
for his research on the physiological
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
basis of memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
storage in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s. He shared the prize with Arvid Carlsson
Arvid Carlsson
Arvid Carlsson is a Swedish scientist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease...
and Paul Greengard
Paul Greengard
Paul Greengard is an American neuroscientist best known for his work on the molecular and cellular function of neurons. In 2000, Greengard, Arvid Carlsson and Eric Kandel were awarded the Nobel Prize for Physiology or Medicine for their discoveries concerning signal transduction in the nervous...
.
Kandel is professor
Professor
A professor is a scholarly teacher; the precise meaning of the term varies by country. Literally, professor derives from Latin as a "person who professes" being usually an expert in arts or sciences; a teacher of high rank...
of biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
and biophysics
Biophysics
Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies included under the branches of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems...
at the Columbia University College of Physicians and Surgeons
Columbia University College of Physicians and Surgeons
Columbia University College of Physicians and Surgeons, often known as P&S, is a graduate school of Columbia University that is located on the health sciences campus in the Washington Heights neighborhood of Manhattan...
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.
Early years
Kandel was born in 1929 in ViennaVienna
Vienna is the capital and largest city of the Republic of Austria and one of the nine states of Austria. Vienna is Austria's primary city, with a population of about 1.723 million , and is by far the largest city in Austria, as well as its cultural, economic, and political centre...
, Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
, in a middle-class Jewish family. His mother, Charlotte Zimels, was born in 1897 in Kolomyya
Kolomyia
Kolomyia or Kolomyya, formerly known as Kolomea , is a city located on the Prut River in the Ivano-Frankivsk Oblast , in western Ukraine. Serving as the administrative centre of the Kolomyia Raion , the city is also designated as a separate raion within the oblast...
, Pokuttya
Pokuttya
Pokuttya or Pokuttia is a historical area of East-Central Europe, between upper Prut and Cheremosh rivers, in modern Ukraine. Historically it was a culturally distinct area inhabitated by Ukrainians and Romanians on the previously unpopulated borderlands between the lands of Lviv and Halych...
(modern Ukraine
Ukraine
Ukraine is a country in Eastern Europe. It has an area of 603,628 km², making it the second largest contiguous country on the European continent, after Russia...
), and came from a well-educated middle-class family. At that time Kolomyya was in Eastern Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
. His father was born in 1898 into a poor family in Olesko
Olesko
Oles'ko is small town in Lviv Oblast of western Ukraine.It was the seat of the rebbes of Alesk, and also the birthplace of Jan III Sobieski, the King of Poland and Grand Duke of Lithuania....
, Galicia (then part of Austria-Hungary
Austria-Hungary
Austria-Hungary , more formally known as the Kingdoms and Lands Represented in the Imperial Council and the Lands of the Holy Hungarian Crown of Saint Stephen, was a constitutional monarchic union between the crowns of the Austrian Empire and the Kingdom of Hungary in...
). 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
Anschluss
The Anschluss , also known as the ', was the occupation and annexation of Austria into Nazi Germany in 1938....
in March 1938. Aryanization
Aryanization
Aryanization is a term coined during Nazism referring to the forced expulsion of so-called "non-Aryans", mainly Jews, from business life in Nazi Germany and the territories it controlled....
(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." He also said 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
Thomas Klestil
Thomas Klestil was an Austrian diplomat and politician. He was elected the tenth President of Austria in 1992 and was re-elected to the position in 1998...
asking him, "How can we make things right?" Kandel said that first, Doktor-Karl-Lueger-Ring should be renamed; Karl Lueger
Karl Lueger
Karl Lueger was an Austrian politician and mayor of Vienna. The populist and anti-Semitic politics of his Christian Social Party are sometimes viewed as a model for Hitler's Nazism.- Career :...
was an anti-Semitic mayor of Vienna, cited by Hitler in Mein Kampf
Mein Kampf
Mein Kampf is a book written by Nazi leader Adolf Hitler. It combines elements of autobiography with an exposition of Hitler's political ideology. Volume 1 of Mein Kampf was published in 1925 and Volume 2 in 1926...
. Second, he wanted the Jewish intellectual community to be brought back to Vienna, with scholarships for Jewish students and researchers. He also proposed to have a symposium on the response of Austria to National Socialism. Kandel has since accepted an honorary citizenship of Vienna and participates in the academic and cultural life of his native city.
After arriving in the United States, and settling in Brooklyn
Brooklyn
Brooklyn is the most populous of New York City's five boroughs, with nearly 2.6 million residents, and the second-largest in area. Since 1896, Brooklyn has had the same boundaries as Kings County, which is now the most populous county in New York State and the second-most densely populated...
, Kandel was tutored by his grandfather in Judaic studies, and was accepted at the Yeshiva of Flatbush, graduating in 1944. He attended Brooklyn's Erasmus Hall High School
Erasmus Hall High School
Erasmus Hall Campus High School is a four-year public high school in the New York City borough of Brooklyn, United States operated by the New York City Department of Education....
, 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
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
.) He wrote an honors dissertation on "The Attitude Toward National Socialism of Three German Writers: Carl Zuckmayer
Carl Zuckmayer
Carl Zuckmayer was a German writer and playwright.-Biography:Born in Nackenheim in Rheinhessen, he was four years old when his family moved to Mainz. With the outbreak of World War I, he finished school with a facilitated "emergency"-Abitur and volunteered for military service...
, Hans Carossa
Hans Carossa
Hans Carossa was a German novelist and poet, known mostly for his autobiographical novels, and his innere Emigration during the Nazi era....
, and Ernst Jünger
Ernst Jünger
Ernst Jünger was a German writer. In addition to his novels and diaries, he is well known for Storm of Steel, an account of his experience during World War I. Some say he was one of Germany's greatest modern writers and a hero of the conservative revolutionary movement following World War I...
." While at Harvard, a place dominated by the work of B. F. Skinner
B. F. Skinner
Burrhus Frederic Skinner was an American behaviorist, author, inventor, baseball enthusiast, social philosopher and poet...
, Kandel became interested in learning
Learning theory (education)
In psychology and education, learning is commonly defined as a process that brings together cognitive, emotional, and environmental influences and experiences for acquiring, enhancing, or making changes in one's knowledge, skills, values, and world views . Learning as a process focuses on what...
and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing 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
Unconscious mind
The unconscious mind is a term coined by the 18th century German romantic philosopher Friedrich Schelling and later introduced into English by the poet and essayist Samuel Taylor Coleridge...
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 oscilloscopeOscilloscope
An oscilloscope is a type of electronic test instrument that allows observation of constantly varying signal voltages, usually as a two-dimensional graph of one or more electrical potential differences using the vertical or 'Y' axis, plotted as a function of time,...
to demonstrate that action potential conduction velocity depends on axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
diameter. The researchers Kandel interacted with were contemplating the technically challenging idea of intracellular recordings of the electrical activity of the relatively small neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s of the vertebrate brain.
After starting his neurobiological work in the difficult thicket of the electrophysiology
Electrophysiology
Electrophysiology is the study of the electrical properties of biological cells and tissues. It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart...
of the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, Kandel was impressed by the progress that had been made by Stephen Kuffler
Stephen Kuffler
Stephen William Kuffler was a pre-eminent Hungarian-American neurophysiologist. Often, he's been referred to as the "Father of Modern Neuroscience". He founded the Harvard Neurobiology department in 1966, and made numerous seminal contributions to our understanding of vision, neural coding, and...
using a much more experimentally accessible system: neurons isolated from marine invertebrates
Marine invertebrates
Marine invertebrates are animals that inhabit a marine environment and are invertebrates, lacking a vertebral column. In order to protect themselves, they may have evolved a shell or a hard exoskeleton, but this is not always the case....
. After becoming aware of Kuffler's work in 1955, Kandel graduated from medical school and learned from Stanley Crain how to make microelectrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...
s that could be used for intracellular recordings of relatively large crayfish
Crayfish
Crayfish, crawfish, or crawdads – members of the superfamilies Astacoidea and Parastacoidea – are freshwater crustaceans resembling small lobsters, to which they are related...
giant axons.
Karl Lashley
Karl Lashley
-External links:*...
, 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
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
in 1957, William Beecher Scoville
William Beecher Scoville
William Beecher Scoville was a neurosurgeon at Hartford Hospital. He performed surgery on Henry Gustav Molaison in 1953 to relieve epilepsy that led to damage of Molaison's hippocampus and left him with memory disorder....
and Brenda Milner
Brenda Milner
Brenda Milner, is a Canadian neuroscientist who has contributed extensively to the research literature on various topics in the field of clinical neuropsychology. -Biography:...
had recently described the patient HM
HM (patient)
Henry Gustav Molaison , famously known as HM or H.M., was an American memory disorder patient who was widely studied from late 1957 until his death...
, who had lost explicit memory storage following removal of the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. 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
Synaptic
Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...
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
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
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
Ladislav Tauc
Ladislav Tauc was born in Pardubice, Czechoslovakia. Tauc was a French neuroscientist, and a pioneer in neuroethology and neuronal physiology. I see that his notability is being questioned...
. Kandel had realized that simple forms of learning such as habituation, sensitization, classical conditioning, and operant conditioning could readily be studied with ganglia
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
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
Aplysia gill and siphon withdrawal reflex
The Aplysia gill and siphon withdrawal reflex is an involuntary, defensive reflex of the sea hare Aplysia californica, a large shell-less sea snail or sea slug...
, 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
Short-term memory
Short-term memory is the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time. The duration of short-term memory is believed to be in the order of seconds. A commonly cited capacity is 7 ± 2 elements...
to additional experiments that included additional physiological processes required for long-term memory
Long-term memory
Long-term memory is memory in which associations among items are stored, as part of the theory of a dual-store memory model. According to the theory, long term memory differs structurally and functionally from working memory or short-term memory, which ostensibly stores items for only around 20–30...
.
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
Classical conditioning
Classical conditioning is a form of conditioning that was first demonstrated by Ivan Pavlov...
, 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 (sensitizationSensitization
Sensitization is an example of non-associative learning in which the progressive amplification of a response follows repeated administrations of a stimulus. An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm...
). 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
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
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
CAMP-dependent protein kinase
In cell biology, Protein kinase A refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP . PKA is also known as 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
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...
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
CREB
CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....
(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. Neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s, second messenger systems, protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
s, ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s, and transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s 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
Principles of Neural Science
First published in 1981 by Elsevier, Principles of Neural Science is a neuroscience textbook edited by Eric R. Kandel, James Schwartz, and Thomas Jessell. The original edition was 468 pages; now on the fourth edition, the book has grown to 1414 pages. The second edition was published in 1985, third...
. Published in 2000 by McGraw-Hill Medical, his textbook focuses on how the brain and neurons work. The book contains visuals and is often used in medical schools for neurological research. Kandel has been a member of the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
, 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 CityNew York City
New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
.
Awards
- Albert Lasker Award for Basic Medical ResearchAlbert Lasker Award for Basic Medical ResearchThe Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for the understanding, diagnosis, prevention, treatment, and cure of disease...
(1983) - Gairdner Foundation International AwardGairdner Foundation International AwardThe Gairdner Foundation International Award is given annually at a special dinner to three to six people for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a precursor to winning the Nobel Prize in Medicine; as of 2007, 69 Nobel...
(1987) - NAS Award for Scientific Reviewing of the National Academy of SciencesUnited States National Academy of SciencesThe National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
(1988) - National Medal of ScienceNational Medal of ScienceThe National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social sciences, biology, chemistry, engineering, mathematics and...
(1988) - Harvey PrizeHarvey PrizeThe Harvey Prize is awarded by the Technion in Haifa, Israel. It is awarded in different disciplines of Science, Technology, Human Health, and Contributions to Peace in the Middle East. Two awards - each of $75,000 - are given away annually...
(1993) - Wolf Prize in MedicineWolf Prize in MedicineThe Wolf Prize in Medicine is awarded once a year by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The Prize is probably the third most prestigious award...
(1999) - Nobel Prize in Physiology or MedicineNobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
(2000) - Charles A Dana Award for Pioneering Achievement in Health (1997)
- Austrian Decoration for Science and Art (2005)
- Benjamin Franklin Medal for Distinguished Achievement in the Sciences of the American Philosophical SocietyAmerican Philosophical SocietyThe American Philosophical Society, founded in 1743, and located in Philadelphia, Pa., is an eminent scholarly organization of international reputation, that promotes useful knowledge in the sciences and humanities through excellence in scholarly research, professional meetings, publications,...
(2006) - Viktor Frankl Award of the City of Vienna (2008)
He is a member of the prize committee for neuroscience of Kavli Prize
Kavli Prize
The Kavli Prize was established in 2005 through a joint venture between the Norwegian Academy of Science and Letters, the Norwegian Ministry of Education and Research, and The Kavli Foundation...
.
External links
- Interview with Kandel June 2006 in German
- Eric Kandel’s Faculty Profile in the Department of Psychiatry at Columbia University
- Eric Kandel's Columbia University website
- Autobiography at the Nobel Prize website
- Science Friday: October 13, 2000 NPR interview
- Eric Kandel - A Nobel's Life
- Eric R. Kandel's United States Patents
- The Kavli Prize Prize Committee Member for neuroscience
- Explains a bit about the textbook Kandel wrote