Eric R. Kandel
Wolf Prize Laureate in Medicine 1999
Eric R. Kandel
Affiliation at the time of the award:
Columbia University, USA
“for the elucidation of the organismic, cellular and molecular mechanisms whereby short term memory is converted to a long term form”.
Employing the marine snail, Aplysia, Professor Eric R. Kandel developed a simple experimental model for the gill and siphon withdrawal reflex in response to stimulation. He studied three forms of learning with this system: habituation, sensitization and classical conditioning. He reconstructed the wiring of neurons used in this set of reflex behaviors and demonstrated that short term memory involves increased transmitter release from pre-existing synaptic connections while long term memory involves growth of new synaptic connections. Simple forms of learning produce these changes by modulating the strength of specific neuronal connections. Following up these studies at the organismic-behavioral level and the cellular network level, Kandel turned his attention to the subcellular and molecular basis of memory. He demonstrated that release of serotonin and the peptide SCP by presynaptic neurons results in increased levels of cyclic AMP and the stimulation of the cyclic AMP dependent protein kinase in the sensory neurons. Repeated release of neurotransmitters results in enhanced covalent modification of proteins. Kandel then identified the critical substrates for this protein kinase including the S-type K+ channel and CREB-like transcription factors. The short term to long term memory switch depends upon translocation of the protein kinase A catalytic subunit into the nucleus and phosphorylated CREB mediated transcription. This in turn results in the induction of the C/EBP transcription factor which has been shown to be essential for the self-sustained maintenance of the long term facilitation of memory. These studies, carried out over thirty years, relate behavior at the organismic level to events at the molecular level. Recently these same molecular events were shown to play a similar role in learning by Drosophila and in the mammalian brain, thus extending the generalization of this research.