Construction sites. Scientists have discovered the signal astrocytes use to tell neurons to build synapses.

Neurons Get Connected Via Glia

NEW ORLEANS--Glial cells once had a reputation as the support staff for neurons, the real movers and shakers in the nervous system. In recent years, however, researchers have gleaned hints that glia, which comprise about 90% of the cells in the brain, do more than just maintenance work. New findings presented here last week at the annual meeting of the Society for Neuroscience suggest that in the crucial task of building synapses--the contact points that allow neurons to talk to one another--glia may even run the show.

The study firms up earlier evidence that glial cells called astrocytes instruct neurons to make synapses and identifies the first extracellular signal known to spur synapse formation in the brain. "That's a pretty big deal," says Michael Ehlers, a neuroscientist at Duke University in Durham, North Carolina.

A clue that glia might be the source of the signal to build synapses came in 2001, when Ben Barres and colleagues at Stanford University reported that lab-grown rat neurons make more synapses in the presence of astrocytes (Science, 26 January 2001, p. 657). To hunt for the chemical messenger, postdocs Karen Christopherson and Erik Ullian in Barres's lab grew astrocytes in culture and filtered the solution bathing the cells before adding it to neurons. To their surprise, these experiments indicated that the chemical that spurs synapse building was a whopper--more than 300 kilodaltons.

Combing the literature for jumbo proteins made by astrocytes produced a short list. It included a protein called thrombospondin, which has a variety of biological roles but whose function in the nervous system was obscure. Purified thrombospondin mimicked the synapse-forming effect of astrocyte culture medium, the team discovered, and the more they added, the more synapses sprouted. Furthermore, the time course of thrombospondin expression in the developing brain mirrors that of synapse formation, they found, putting the protein in the right place at the right time to hook up neurons.

It makes sense that a large, multipurpose protein like thrombospondin would turn out to be behind synapse formation, Ehlers says. "It can bind and regulate all sorts of things. You can imagine it bringing together a variety of surface proteins, a variety of components needed to assemble something like a synapse." The research raises the exciting possibility that thrombospondin may contribute to the modification of synapses thought to underlie learning and memory, points out Douglas Fields, a neuroscientist at the National Institutes of Health in Bethesda, Maryland.

Related sites
Glia basics
Barres's site
Ehlers's site
Fields's site