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May 28, 2009 — Researchers have identified
the locking mechanism that allows some neurons to form synapses to pass
along essential information. Mutations of genes that produce a critical
cell-adhesion molecule involved in the work were previously linked to
The discovery -- captured with fluorescent imaging of excitatory
neurons harvested from rat pups shortly after birth and studied in
culture as they continued to develop -- is described in a paper in the
journal Neural Development.
"We've caught two neuronal cells in the act of forming a synapse,"
said principle investigator Philip Washbourne, professor of biology at
the University of Oregon. He describes the cell-adhesion neuroligin
proteins on the membranes of receptor neurons as "molecular Velcro."
The research team of six UO and University of California, Davis,
scientists found one of many finger-like filopodia, or spines, that
reach out from one neuron is nabbed by neuroligin molecules on the
membrane of another neuron. In turn, neuroligins recruit at least two
other key proteins (PSD-95 and NMDA receptors) to begin building a
scaffold to hold the synapse components in place. The moment of locking
is captured in a video (link below) that will appear with the paper's
final version at the journal's Web site.
Two neuroligin family members (3 and 4) have been linked to autism in the last decade.
"Chemical synapses are the primary means for transmitting
information from one neuron to the next," said Washbourne, who is a
member of the UO's Institute of Neuroscience. "Synapses are initially
formed during development of the nervous system, and formation of
appropriate synapses is crucial for establishing neuronal circuits that
underlie behavior and cognition. Minor irregularities can lead to
developmental disorders such as autism and mental retardation, and they
may contribute to psychological disorders."
The findings, he added, reflect a clearer understanding of how
synapses form, providing a roadmap for research that someday may lead
to new therapies or a cure for autism, a brain development disorder
that affects a person's social and communication abilities. The
disorder affects 1 in every 150 American children, according to the
Autism Society of America.
The new window opened by Washbourne's team captures the essence of
synapse development, which occurs over and over among the estimated 100
billion neurons that make some 100 trillion synapses in a single human
being. That leaves a lot of room for errors in the DNA-driven
instructions for synthesizing molecules responsible for synapse
formation, Washbourne said.
"Basically," Washbourne said, "we have found mechanisms by which two
very important molecules, NMDA and PSD-95, are brought to a newly
Co-authors with Washbourne were postdoctoral researches Stephanie L.
Barrow and Eliana Clark at UC-Davis, A. Kimberley McAllister, a
professor in the UC-Davis Center for Neuroscience, and John R.L.
Constable, a postdoctoral researcher in Washbourne's UO lab. Constable
is funded by a medical research fellowship provided by Oregon Health
and Science University in Portland.
The National Institute of Neurological Disorders and Stroke
(National Institutes of Health), the Florida-based non-profit Whitehall
Foundation and New York-based Autism Speaks, the nation's largest
autism science and advocacy organization, funded Washbourne's research.
McAllister was funded by the Pew Charitable Trusts and National Eye
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