Wiring the Brain

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Image: TIMOTHY GOMEZ

That the developing nervous system can wire itself¿making countless essential connections in an ever expanding network¿is still a wonder, but scientists have discovered some of the signals that budding nerve cells use for guidance. In the March 9th issue of Science, Timothy Gomez of the University of Wisconsin, Nicholas Spitzer of the University of California at San Diego and their colleagues describe one such signal: they have discovered that filopodia¿fingerlike projections on the ends of growing nerve cells¿scout out their surroundings using ultrashort bursts of calcium.

"These bursts, which usually occur at the very ends of the filopodia, are extremely brief¿about a 300-millisecond pulse¿which may explain why they were undetected in earlier studies," Gomez says. "Since many other types of cells have these fingerlike projections, we believe that these brief calcium bursts may be a universal signaling mechanism for motile cells."


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The researchers introduced a fluorescent calcium marker into spinal nerve cells harvested from developing frog embryos. They then placed the cells into eight different chemical environments and, using a camera attached to a microscope, recorded the resulting calcium bursts (colored red and fuschia in the image shown here). As it turned out, the frequency of the bursts varied with the kinds and concentrations of chemicals the filopodia encountered, as well as with their positioning. Calcium bursts on one side of a growing cell, for instance, caused the cell to reorient itself and set forth in another direction.

Understanding how these connections form could ultimately be of clinical significance. "Many kinds of birth defects and a large fraction of spinal cord defects appear to be associated with problems in the formation of nerve connections in the developing embryo," Spitzer remarks. "We want to understand how the normal brain is put together, so we can understand the cases in which it is not put together correctly."

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