The 2000 Nobel Prize in Physiology or Medicine rewarded three scientists who deciphered the signalling pathways that regulate some of the brain’s most important functions. The primary switches for these processes are neurotransmitters: chemical messengers sent from one nerve cell to another across the tiny junctions, or synapses, that separate them.
Arvid Carlsson overturned conventional wisdom by showing that the chemical dopamine is an important neurotransmitter in the brain. Dopamine was presumed to be merely a precursor to a more important neurotransmitter, noradrenaline, but Carlsson devised a highly sensitive test, which allowed him to detect that dopamine was concentrated in parts of the brain that control movement. Animals’ movements froze when they were given a drug that depletes the brain of several neurotransmitters, and Carlsson found that their movements miraculously returned when he gave them the chemical L-dopa, which the brain converts to dopamine. This eventually led to the use of L-dopa to treat Parkinson’s disease, the symptoms of which are caused by a lack of dopamine; and Carlsson also provided evidence that some forms of mental illness are associated with the disrupted regulation of dopamine.
Paul Greengard demonstrated what happens after transmitters such as dopamine and noradrenaline arrive at their intended destinations in synapses. He showed that they set off a chemical chain reaction, and he pieced together the complex molecular cascade of events that occurs when dopamine meets its target receptor. A so-called second messenger is released, switching on a protein that in turn activates a host of other proteins by adding phosphate molecules onto them. This activation mechanism, phosphorylation, creates a profound change in the form and function of many proteins that alter the way that the nerve cell behaves, and these proteins can be deactivated by removing the phosphate molecules.
Eric Kandel revealed how memories are formed through chemical cascades similar to those identified by Greengard. Using the giant marine snail, Aplysia, which has a simplified nervous system, Kandel found that the protective reflex the animal uses to guard its gills is modified by a form of learning triggered by changes at synapses. Subsequent work uncovered that different types of memory, from marine snails to man, are caused by different changes in synapses. Short-term memories are formed when a weak stimulus causes phosphorylation of protein pores that allow more neurotransmitter molecules to be released. Long-term memories require stronger, longer-lasting stimuli, which phosphorylate a different set of proteins, and which also order the creation of new proteins that alter the shape and function of the synapse, the effect of which is to allow more neurotransmitters to be released.
By Sophie Petit-Zeman, for Nobelprize.org
This Speed read is an element of the multimedia production “Nerve Signaling”. “Nerve Signaling” is a part of the AstraZeneca Nobel Medicine Initiative.
First published 16 September 2009