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The brain’s ability to transmit and process information requires a lifelong commitment to maintaining the integrity of synapses, according to James Morgan, PhD, co-chair, St. Jude Children's Research Hospital Developmental Neurobiology.
This long-term commitment requires proteins called synaptotrophins, the prototype of which is Cbln1, to maintain countless millions of synapses in good working order. In the absence of such proteins, the synapses weaken and eventually fall apart. Morgan is senior author of a report on studies of a model used to make these findings; the report appears in the November 15 issue of Nature Neuroscience.
Morgan’s team found that nerves in the cerebellum called granule cells release a protein called Cbln1 from their axons. This maintains their synaptic connections with dendrites of the Purkinje cells, large nerves that are aligned like dominos across the upper part of the cerebellum and send information to other parts of the brain. The action of the granule cells also helps prevent other nerves from impinging on these synapses.
The researchers also found that Cbln1 is a key player in the establishment of long-term depression (LTD, a molecular form of memory) at the synapse made by the axon of the granule cell (the parallel fiber) and the Purkinje cell. The authors propose that this occurs through a protein in the post-synaptic spine (dendrites) of Purkinje cells called the orphan delta-2 glutamate receptor. They also propose that delta-2 glutamate receptor’s mediation of the Cbln1 action represents a general strategy used by synaptosomes throughout the brain to maintain proper synapses between specific pairs of nerves.
"These proteins and their pathways might represent potential targets for therapeutic intervention in neurological and psychiatric diseases," said Morgan, who has received a five-year RO1 grant from NIH to continue this work.
Other St. Jude authors include Dashi Bao, PhD, Leyi Li, PhD, Jennifer Parris and Yongqi Rong, MD, all of St. Jude Developmental Neurobiology.
St. Jude does both laboratory and clinical research in order to find cures for catastrophic diseases of children. Much of this research, especially in the laboratory, leads to discoveries of the basic workings of the body's cells. Therefore, some of our work has broader implications than childhood diseases and provides insights into adult diseases as well.
Last update: December 2005