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Seeing synapses: new ways to study nerves.

Studying the linkages among the brains billions of nerve cells is a bit like maneuvering through a dense thicket while trying not to break any branches. Tangled cellular appendages, called axons and dendrites, form a virtually impenetrable network for anyone who wants to observe nerve-to-nerve connections intact.

Nevertheless, two groups of neurobiologists are making headway. By using a nerve-muscle junction as a surrogate, one team has demonstrated how permanent changes in nerve connections can occur, changes that may underlie learning. A second team used special molecules, unleashed by lasers, to trace the circuitry created by these linkages. Both groups reported their findings this week at the annual meeting of the American Association for the Advancement of Science, held in San Francisco.

During development, nerve cells reach out to many other cells. Ultimately, however, they form only a few permanent connections, called synapses, between their axons and the dendrites of particular target cells. Experience can further modify these synapses.

To understand this paring of initial connections and subsequent modifications, Jeff W.. Lichtman of Washington University School of Medicine in St. Louis studies neuromuscular junctions -- the sites where nerve endings reach into muscle fibers. He and his colleagues observe these junctions intact in anesthetized mice. They label an axon's terminals with one dye and receptor molecules on the target cell with another. Thus they can see hourly, even weekly, changes in a given synapse.

"He's got the only real data [along] a time course and [with] a causal nature," comments Scott E. Fraser of the California Institute of Technology in Pasadena. "That's quite exciting."

Neurobiologists have traditionally viewed axons as rivals that compete with one another during nervous system development to create a particular synapse. "The axon that wins that competition is more or less married to that postsynaptic cell," explains Lichtman. But as with many courtships, the dynamics of the relationship are not as they first appear. Lichtman's surveillance has revealed that postsynaptic cells play a key role in choosing the axons with which they will tie the knot, so to speak.

Initially, target muscle cells possess lots of receptors, and several axons form synapses with each cell. But then some receptors disappear, and eventually the axons at those spots withdraw. However, the successful axon does not expand onto the spots vacated by other axons, Lichtman says.

To investigate this dynamic further. he and colleague Rita J. Balice-Gordon exposed a tiny section of the target-cell surface to a chemical that blocks receptor activity. Afterward, they allowed each mouse to resume its normal life but reexamined these synapses almost weekly for a month.

After a week, the distribution of the dyes revealed that paring had begun; a week later, the receptors at that spot and their connecting nerve endings had disappeared, Lichtman reports. "A relatively simple manipulation of the activity of the target cell can cause a dramatic change in the synaptic input of that cell, [a change] that is permanent," he concludes.

At Duke University in Durham, N.C. Lawrence Katz takes a different tack. His group bathes slices of mammalian brain in a solution of caged glutamate, a chemical that cannot excite the nerve cells while encased. He and his colleagues then monitor activity in one nerve cell as they scan the slice with a laser.

At each spot, the laser briefly releases glutamate, which activates the nerve cell there. But the monitored nerve cell reacts only if the activated cell connects to it, a technique that enables the researchers to map just that particular nerve cell's connections. Thus the Duke team witnessed how developing nerves first make many connections but later pare those linkages in a specific pattern, Katz reports.
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Author:Pennisi, Elizabeth
Publication:Science News
Date:Feb 26, 1994
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