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Making light work of regulating locomotion in vertebrates

Munich, 09/17/2009

Together with colleagues based in the USA, scientists from Ludwig-Maximilians-Universität (LMU) in  Munich have begun to uncover the cellular mechanisms that regulate locomotion in vertebrates. The scientists used an artificial receptor to stimulate specific nerve cells in zebrafish with light. The approach, known as optogenetics, involves a combination of gene expression in specific cell types and the use of light to manipulate neuronal activity. (Nature, 17 September 2009)

Professor Dirk Trauner at LMU Munich´s Department of Chemistry and Biochemistry and colleagues at the University of California, Berkeley developed a photoreceptor that makes it possible to control the activity of neurons with light. The receptor is based on a ligand-gated ion channel, a protein that allows ions to cross the cell membrane upon binding of a specific compound. To control the activity of neurons, the ligand is coupled directly to the modified receptor via a light-sensitive chemical bond: Only upon illumination does the ligand bind at the correct position to activate the receptor. By means of genetic engineering techniques, the modified receptor, called LiGluR, can be expressed in various neuronal cell types. As a result, their activity can be regulated by light in a targeted fashion. This strategy has now allowed researchers at the University of California, Berkeley and San Francisco to study the influence of different types of nerve cells on the behaviour of zebrafish.

The scientists were able to assign a previously unrecognized role in the control of the neuronal module that underlies spontaneous swimming behaviour in zebrafish to the so-called Kolmer-Agduhr neuron. These cells were first described over 75 years ago, but their function has remained a mystery. The cells are interesting to biologists because they bear many hair-like cilia, tiny sensory organelles that are in direct contact with the cerebrospinal fluid. They may therefore respond to chemical signals in the spinal canal. Genetic silencing of Kolmer-Agduhr cells reduced the frequency of spontaneous swimming. This finding implies that the cells provide signals necessary for this type of behaviour. Kolmer-Agduhr cells are closely related to similar cells that exist in mammals and other vertebrates.

“This work should have a major impact on the understanding of locomotion in vertebrates and provides a nice example for the usefulness of chemical technology in neuroscience,” says Professor Trauner. He explains that there have been some doubts about whether LiGluR and related synthetic systems would be competitive as optogenetic tools with the naturally occuring light-gated channels, and whether or not it would be embraced by the neuroscience community. “Hopefully these doubts will now be laid to rest,” Trauner concludes. (SA)

“Optogenetic dissection of a behavioural module in the vertebrate spinal cord”,
Claire Wyart, Filippo Del Bene, Erica Warp, Ethan K. Scott, Dirk Trauner, Herwig Baier and Ehud Y. Isacoff
Nature, 17 September 2009, p. 407-410
DOI: 10.1038/nature08323

Professor Dr. Dirk Trauner
Department of Chemistry and Biochemistry
Phone: +49 (0) 89 / 2180 – 77800
Fax: +49 (0) 89 / 2180 – 77972

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