UC Davis researchers visualize formation of a new synapse

"Axons of one neuron grow toward the dendrites of neighboring neurons. As they do so, finger-like structures called filopodia extend and retract rapidly from the tip of the axons and eventually make a stable contact with the dendrite. We can then see neuroligin accumulate at these new contact sites very rapidly, possibly stabilizing adhesion between the two cells. After a few minutes, more neuroligin accumulates at this contact site, bringing NMDA receptors in with it, which is then followed by a much slower recruitment of PSD-95."

The images that accompany the study show that, indeed, the two synaptic receptor proteins, PSD-95 and NMDA, are independently recruited to the site of synapse formation once the connections are locked in place by neuroligin.

"Synapses are basically specialized sites of cell adhesion that are initially formed during development of the nervous system. Formation of viable synapses is crucial for establishing neuronal circuits that underlie behavior and cognition," said study senior author Philip Washbourne, a UC Davis postdoctoral fellow when the study was initiated and now an assistant professor of biology at the University of Oregon.

McAllister and Barrow are continuing to capture images of the dynamics of other important molecules during synapse formation. Their goal is to create a virtual cinematic representation that includes many of the molecules that play important roles in the formation of a normal, working synapse.

"Many people think that improper synapse formation leads to the symptoms of autism," McAllister said. "This research will allow us to learn more about how synapses form to better understand what aspects of synapse formation might be altered in the disorder."

Other study authors include Faten El-Sabeawy of UC Davis, Eliana Clark, formerly of UC Davis, and University of Oregon postdoctoral fellow John Constable.

The study was funded by the Pew Charitable Trusts, the National Eye Institute, the John Merck Fund, a UC Davis Vision Science Training Grant, the Whitehall Foundation and Autism Speaks.

UC Davis School of Medicine is among the nation's leading medical schools, recognized for its specialty-and primary-care programs. The school offers combined medical and master's degree programs in public health, business administration and rural health, as well as a combined medical and doctoral degree for physician scientists interested in addressing specific scientific, social, ethical and political challenges of health care. Along with being a leader in health-care research, the school is known for its commitment to people from underserved communities and a passion for clinical care. For more information, visit UC Davis School of Medicine.