Eric Kandel - Molecular Changes During Learning

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.