Sci. Aging Knowl. Environ., 3 March 2004
All-or-None No More
Brain cells mete out neurotransmitters
"Reduce, reuse, recycle" isn't just an environmental mantra. According to a new study, it's standard procedure for some brain cells, which utilize the tiny sacs that carry neurotransmitters more than once. The work challenges the standard view that the sacs release their contents in one burst, a finding that might someday help researchers develop better treatments for illnesses in which neurotransmitter supplies plunge, such as Parkinson's disease.
When an electrical impulse hits the end of a neuron, small capsules called vesicles pour neurotransmitters into the synapse, the junction between nerve cells, but scientists don't understand the details. In one scenario, a vesicle merges with the cell membrane and dumps its entire contents. In an alternative scheme, known as kiss-and-run, the vesicle releases a slug of neurotransmitter through a tiny opening in the membrane and then detaches and floats away. Studies have confirmed the existence of both mechanisms in chemical-releasing, nonneuronal cells that carry large vesicles and are easier to study. However, because observing rapid changes that occur in the tiny space of the synapse is difficult, researchers haven't verified kiss-and-run in neurons.
To tackle the question, neuroscientist David Sulzer of Columbia University in New York City and colleagues used a minute carbon-fiber electrode to count molecules exiting the neuron. The team applied the technique to cultured rat brain cells that spill the neurotransmitter dopamine. Usually, chemically stimulating a cell produced a single burst of dopamine. But occasionally multiple peaks of decreasing size appeared. What happens is more like a French kiss, says Sulzer. A vesicle attaches to the membrane and releases several pulses of dopamine; the researchers can't tell whether the pore opens and closes rapidly or narrows and widens. The pattern of pulses doesn't match other possible explanations, such as two vesicles releasing nearly simultaneously. The paper is the first to show that vesicles in neurons don't always release all their contents, Sulzer says: "This could be an important form of regulating neurotransmission that no one has recognized before." It might also save the cell time and energy. Vesicles that fuse with cell membrane have to be replaced. But if the containers dock temporarily, a cell can refill and reuse them. Sulzer adds that the results might help researchers devise treatments for Parkinson's disease, in which dopamine-releasing neurons in a particular brain region perish. Coaxing vesicles to release more neurotransmitter might somewhat compensate for the decline in dopamine output, he says.
Analytical neurochemist Mark Wightman of the University of North Carolina, Chapel Hill, lauds the study for "discovering a basic mechanism of how the human brain works." Recycling is a prudent move for neurons, he adds, because they carry few vesicles. Dopamine-releasing neurons are unusual, cautions neuroscientist Charles Stevens of the Salk Institute for Biological Studies in San Diego, California. They use a different neurotransmitter and have a different structure than do most other brain cells. So researchers need to determine whether vesicles behave the same way in common neurons, he says. That work will reveal whether other neurons are as frugal as the dopamine-producing ones.
March 3, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150