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Fragile X, Down Syndromes Linked to Faulty Brain Communication,,Stanford Researcher Finds

drome's name suggests, the responsible gene, called Fmr1, is located on the X chromosome. Because boys have only one X chromosome while girls have two, boys are usually more severely affected when Fmr1 is mutated. Girls are not immune to the condition, however. A phenomenon called X-inactivation, which randomly silences one member of every X chromosome pair, creates a mosaic of affected and unaffected nerve cells in the brain.

In some conditions linked to the X chromosome, such as hemophilia, the normal cells can cover for their useless peers. Not so for an elite corps of brain neurons. Here, where cooperation and communication are key, a few deadbeats in the mix can be disastrous.

The researchers' discovery of the muddled communication networks in the brain hinged on two advances. One was their creation of an Fmr1 mosaic mouse with brain characteristics similar to those of people with Fragile X. The other was the use of specialized microscopes and tiny needles to eavesdrop directly on individual conversations between two cells. Before this study, investigators relied on a strain of mice in which every cell carried a mutated Fmr1 gene, and they inferred how cells communicated by results from experiments on groups of cells.

The new approach allowed Madison's team to see that cells with a mutated Fmr1 gene have a very selective flaw: they are less likely than normal cells to reach out and form connections, or synapses, with their neighbors. Although normal cells in the mosaic brain can reroute around these potential dead ends, the resulting neural network has fewer cells and is less complex. "If, for example, 10 percent of normal nerve cells are now responsible for half your neural network, the information-carrying capacity of your brain goes down," he said.

Madison said the findings from this study point researchers in a new direction. "Until now the emphasis in the field has been on the receiving, or post-synaptic, side of the synapse," h
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