The 2000 Nobel Prize in Physiology or Medicine was awarded to three pioneering neuroscientists "for their discoveries concerning signal transduction in the nervous system." Signal transduction is the process by which nerve cells communicate. Each winning neuroscientist looked at changes that occur within nerve cells. The three winners will share the prize of nine million Swedish crowns, or $914,700. The prizes will be presented in Stockholm, Sweden, in December of 2000.

And the Winners Are...

Arvid Carlsson, M.D.

Carlsson knew that a drug called reserpine decreased levels of other neurotransmitters; would it also affect dopamine levels? Research animals given reserpine lost control of spontaneous movement. Because taking dopamine away led to movement problems, would putting it back fix the problem? To find out, Carlsson gave the animals that were treated with reserpine a precursor to dopamine called L-dopa. L-dopa eliminated the movement problems in the research animals. Carlsson realized that these symptoms were similar to those of people with Parkinson's disease.

It is now known that dopamine levels are decreased in the brains of Parkinson's patients, especially in an area called the substantia nigra. Treating patients with L-dopa restores dopamine levels in their brain, thus lessening symptoms such as movement problems. L-dopa is still the most common treatment for Parkinson's disease. This basic research has also aided treatments for schizophrenia and depression.

Paul Greengard, Ph.D.

How do nerve cells communicate? A nerve cell produces an electrical signal called an action potential. The action potential causes the release of a neurotransmitter (such as dopamine) from its end (nerve terminal). A second nerve cell responds to the neurotransmitter by producing its own electrical signal. One key event in this signaling is phosphorylation. Phosphorylation is the process by which proteins are modified by having phosphate groups attached. This changes the form, and thus the function of the protein. These proteins play a role in affecting signaling by altering the properties of the nerve cell. Phosphorylated proteins might make a nerve cell more "excitable," meaning it is more likely to send a signal. This series of events is called signal transduction, and it is how nerve cells send signals. When this signaling cascade is disrupted, for example when dopamine signaling is abnormal, disorders such as Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder can result. A deeper understanding of how signaling works under normal circumstances has helped researchers treat disorders in which signaling is abnormal.

Greengard is donating his share of the prize money to a fund at The Rockefeller University for women in biomedical research. The fund is in honor of his mother, who died giving birth to him.

Eric Kandel, M.D.

The sea slug is a useful research animal because it has relatively few neurons (approximately 20,000) in its entire nervous system. Also, the neurons are always wired in the same way. However, the strength of the connections between neurons can change and be influenced by learning. Learning involves making memories, and memories bring about changes in the brain. Kandel showed that memories alter synapses in the brain. This by itself was big news, but Kandel pushed further to show that short-term memory involves changes in already existing synapses, whereas long-term memory involves creating new synapses.

Sea slugs have a reflex that protects their gills, the structures that help them breathe (similar to our lungs). This reflex is called the "gill-withdrawal reflex." Kandel used this reflex to probe learning in the slugs. He found that some types of stimuli caused this reflex to strengthen, and that it would be stronger for several days or a week. This represents simple learning.

Kandel wondered what was happening at the level of the synapse during learning. He discovered that there is an amplification at the synapse between the sensory nerve cell (sensing the stimulus, like your ears hear sound) and the motor nerve cell that tell muscles to perform the protective gill-withdrawal reflex. This would be like your mom calling to tell you to come home from a friend's house. Your mom's call is the stimulus, your coming home is the action--like the gill-withdrawal reflex. What is strengthened is the telephone call: maybe it is clearer, or louder. Each time she calls, you know you have to go home, and you start to learn what the phone call means. This is simple learning.

The phosphorylation of proteins that Greengard studied was important for Kandel's work, too. It turns out that short-term memory involves a series of events at the synapse in which phosphorylation of proteins is key. Long-term memory has even more dramatic effects on the synapse, changing the number of proteins in the synapse, and even altering the synapse's shape!

Kandel has expanded his studies to include mice. Many of the changes seen in the sea slugs are seen in mice. This suggests that this work may be applicable to humans, too. Understanding how memory formation and learning work at the synaptic level will aid in the development of drugs to treat neurological disorders such as Alzheimer's disease and dementia.

References:

1. Rockefeller University coverage of Paul Greengard
2. Nobel Prize Winners (Neuroscience) - from Neuroscience for Kids