The ability of the brain to transmit and process information requires a lifelong commitment to maintaining the integrity of synapses--the special connections that permit the passage of nerve impulses from one nerve cell to another, according to investigators at St. Jude Children's Research Hospital and colleagues in Hokkaido University School of Medicine (Japan). A report on this work appears in the November 15 issue of Nature Neuroscience.

This long-term commitment requires proteins called synaptotrophins, the prototype of which is Cbln1, to maintain countless millions of synapses in good working order, the researchers said. In the absence of such proteins, the synapses weaken and eventually fall apart. This not only compromises nerve transmission, but also provides the opportunity for other nerves to extend their axons toward these faltering synapses and make inappropriate connections that further disrupt brain function.

"Traditionally, studies in this field emphasized the development of the nervous system, and focused on how axons navigate to the correct part of the brain and then recognize and make specific synaptic contacts with the correct type of nerve cells," said James I. Morgan, Ph.D., a member and co-chair of the Department of Developmental Neurobiology at St. Jude. "It now appears that there are other processes at work throughout adult life that maintain the integrity and function of these connections once they have formed."

The idea that synapses require maintenance factors in the adult is not new, although the identification of specific substances that contribute to this process has proven elusive, Morgan said. Therefore, the researchers used a laboratory model of the cerebellum to identify proteins that maintain a specific set of synaptic connections. Using this model they found that Cbln1 maintains correct synaptic connections after they have been established.

The St. Jude team showed that Cbln1 maintains the con
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Contact: Carrie Strehlau
Carrie.Strehlau@stjude.org
901-495-2295
St. Jude Children's Research Hospital
15-Nov-2005

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