Using a state-of-the-art technique to map neurons in the spinal cord of a larval zebrafish, Cornell University scientists have found a surprising pattern of activity that regulates the speed of the fish's movement. The research may have long-term implications for treating injured human spinal cords and Parkinson's disease, where movements slow down and become erratic.
The landmark study, published in the March 1 issue of Nature, maps how neurons, or nerve cells, in the tail end of the fish's spinal cord become active during slow movements, while cells further up the spinal cord activate as movements speed up.
The research opens a door toward basic understanding of the architecture and function of nerves in the spinal cord, said Joseph Fetcho, Cornell professor of neurobiology and behavior. While no one knows exactly how the research relates to other vertebrates, it could help scientists assess whether nerves in an injured spinal cord are regrowing normally, he said. The paper's lead author, David McLean, a postdoctoral researcher in Fetcho's laboratory, made the initial discovery.
The researchers rendered the zebrafish incapable of slow movements by removing specific neurons in the lower spinal cord with laser beams. When nerves farther up the backbone were removed, the fish had difficulty moving fast.
"No one had any idea that organization like this existed in a spinal cord," said Fetcho. "Now that we know the pattern, we can begin to ask how that changes in disease states."
The researchers worked with 4-millimeter-long larval zebrafish (Danio rerio) because they are transparent and researchers can see their cells. Fetcho and colleagues injected the spinal cord with a fluorescent dye, which then lit up when calcium ions flooded in as the nerve cells activated when the fish moved. A confocal microscope with lasers allowed the researchers to image the cells at very high resolutions. Using this setup, they watched nerve cells light up as the animals moved at different speeds.
In Parkinson's disease, researchers believe that a neurotransmitter released by brain cells may contribute to activating a system of nerves and muscles that allow for faster movement. They suspect that damage to these brain cells may disrupt the release of dopamine, further complicating free movement. Fetcho and his group are building a transgenic line of fish with those brain cells labeled so they can be targeted and removed with lasers.
Fetcho is a key new hire in Cornell's New Life Sciences Initiative. His work uses genetics and state-of-the-art imaging techniques to reveal and enhance basic understanding of how movements are produced by the brain and spinal cord of vertebrates.
Melina Hale, an assistant professor at the University of Chicago's Department of Organismal Biology and Anatomy and a former postdoctoral researcher in Fetcho's laboratory, conducted the work using lasers to remove nerve cells.
The study was funded by the National Institutes of Health and the Ministry of Education, Science, Technology, Sports and Culture of Japan.