The National Science Foundation (NSF) has awarded University of Utah School of Biological Sciences Distinguished Professor Erik Jorgensen and John A. Moran Eye Center scientist Bryan Jones funding as part of NSF’s Next Generation Networks for Neuroscience (NeuroNex) program. They join an international group of scientists that will explore the connections between neurons, known as synapses.

“Synapses are contacts between nerve cells in your brain. Think of all the stars you can see on a moonless night. Multiply that by 100 billion. That’s how many synapses you have that can hold and process a lot of information,” said Jorgensen. “Your grandmother lives there, your childhood friends, embarrassment, fear, love, and hate. We want to understand how synapses work, how they change to store a memory, how they become corrupted when we forget, or why they die as we pass into dementia.”

The NSF will disperse more than $50 million over five years to four interdisciplinary teams, including $17.5 million for the U.S. component of the team of which Jones and Jorgensen are a part that is led by the University of Texas, Austin. Their project will examine the relationship between the weight, or strength, of synapses and their structural components. For example in the retina, synapses allow for the communication between neurons involved in the detection of light and the processing of information associated with vision, such as contrast, color, and movement.

“Understanding how the synapses change in retinal disease is crucial to understanding how to design therapeutic interventions,” Jones explained. “For a long time, it was presumed that the communication between neurons at synapses was an all or nothing event. But now we know that synaptic communication is much more nuanced.”

Using multidisciplinary approaches, cutting-edge imaging technologies and cyber resources, the research team will generate data to predict how specific neural circuits form and function. Because recent research has uncovered the important role of differences in synaptic strength, the new project will explore how factors such as size, connectivity, volume, cellular resources and protein composition help shape these nanometer-sized structures and the effects that these differences have in the brain.

“To understand the synapse we need to be able to see them, to study their architecture, and track the proteins in the synapse. How can we do that? We use an electron microscope to visualize the structure of the synapse,” Jorgensen said. “We can move in closer to determine the atomic structure of protein complexes, or we can stand back to see vast fields of synapses and their interconnections. The University of Utah and its leadership have invested in these new technologies, and we have become a leading institution in the world exploring this new terrain of biology.”

The consortium will share reagents, methods and data to work together to characterize  the formation of synapses, their function and their decline using electron microscopes. Jorgensen’s lab will use a Zeiss Gemini transmission-mode scanning electron microscope that was awarded to the U by the Howard Hughes Medical Institute.

“Our second and newest electron microscope, recently gifted by the Lawrence T. & Janet T. Dee Foundation, will be crucial to this effort,” said Jones. “It provides a sensitive camera and another transmission electron microscope that we will need to visualize synapses at multiple angles and to perform the work required for this grant.”

“There’s still so much we don’t know about how the brain works, and one of the keys to unlocking those mysteries is finding out more about specific neural circuits,” said NSF NeuroNex Program Director Floh Thiels. “This requires bringing together researchers from fields including chemistry, biology and computer science and engineering, and applying the latest analysis techniques to the data they produce. This has been a goal for neuroscientists for years, and what we will see from this network of researchers is a new chapter of international collaboration and coordination.”

Other collaborators on the team are Kristen Harris, Mark Ellisman, Terrence Sejnowski and Robert Reid of UT Austin; Alice Ting at Stanford University; Mark Ellisman at the University of California, San Diego; Clay Reid at the Allen Institute for Brain Science; Davi Bock at the University of Vermont; Narayanan Kasthuri at the University of Chicago; Linnaea Ostroff at the University of Connecticut at Storrs; Terrence Sejnowski and Uri Manor at the Salk Institute for Biological Studies; Joshua Vogelstein at Johns Hopkins University; and James Carson at Texas Advanced Computing Center. Viren Jain at Google (U.S.) will also participate.

This story was adapted from a release by Elizabeth Neff at the John A. Moran Eye Center and from the University of Texas, Austin.