Arvid Carlsson discovered that the neurotransmitter dopamine is concentrated in the basal ganglia. Treating dopamine loss eases the symptoms of Parkinson's disease.

Nobel Prize Celebrates the Synapse

Pioneering work in deciphering how neurons communicate has landed three researchers the Nobel Prize in physiology or medicine. Sharing the $912,000 prize, announced in Stockholm on 9 October, are Arvid Carlsson of the University of Gothenburg in Sweden, Paul Greengard of Rockefeller University in New York City, and Eric Kandel of New York's Columbia University. Their research has led to treatments for numerous nervous system diseases as well as insights into learning and memory.

"These people are all towering figures" in the field, says neurobiologist Charles Stevens of the Salk Institute for Biological Studies in La Jolla, California. He and other neuroscientists laud the Nobel committee's decision to honor several research lines, spanning nearly 5 decades, that together laid the groundwork for understanding neurotransmission.

In the 1950s, Carlsson, now 77, overturned conventional wisdom by proving that dopamine--once thought to be a mere building block in the synthesis of the neurotransmitter norepinephrine--was an important nervous system messenger in its own right. He and others later discovered that Parkinson's disease, which causes rigidity and tremors, results from a lack of dopamine in the brain. That find led to the use of the dopamine precursor L-dopa as a therapy for Parkinson's patients. The complex connection between neurotransmitter levels and mental state has also spawned a wealth of drugs that fight psychosis and depression. The Swedish researcher admits that the Nobel Prize for years has influenced his own mental state. "I started thinking in the 1960s that I might be considered," Carlsson told ScienceNOW. "I've been up and down about it many times since then."

Greengard, 74, took Carlsson's insights several steps further in the 1960s by exploring how dopamine, norepinephrine, and serotonin control transmission of nerve signals at the synapse, the junction between communicating nerve cells. Greengard showed that the three neurotransmitters trigger the addition or removal of phosphate groups to proteins involved in nerve signaling, prompting them to interact with other proteins in a cascade of phosphorylation in and around the synapse. The rapidly changing milieu alters nerve cell properties--for example, increasing its sensitivity to stimulation. "This prize is really a celebration of the synapse," says Corey Goodman, a neuroscientist at the University of California, Berkeley.

The discovery that protein phosphorylation is key to nerve cell signaling helped inspire the research of Kandel, 70. He studied learning and memory in the sea slug Aplysia, which has large nerve cells that are easy to manipulate. He found that the ease with which ions such as calcium pass through a cell membrane--and thus transmit a nerve impulse--depends on whether the proteins forming the membrane's pore are phosphorylated. Based on these findings, Kandel showed that short-term and long-term memory are related to the strength and duration of nerve impulses, and that new proteins are synthesized to maintain long-term memory.

Related sites

The Nobel Foundation

Eric Kandel's home page

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