By Tara Roberts

With 26 letters, the English alphabet can build tens of thousands of words. With 10,000 kinds of cells, the human brain can build a number of connections so vast it’s hard to grasp.

Like letters arranged into words, these connections must be “spelled” right as the brain develops.

“Because the nervous system is wired specifically, most of us make more or less the same words,” explains Peter Fuerst, an assistant professor of biological sciences at the University of Idaho.

Incorrect connections in the brain are like nonsense words – they don’t work with the whole, potentially leading to developmental disorders, autism or sensory deprivation. Other times, neurons that make inappropriate connections function like a repeated word or exclamation mark, exaggerating normal behavior in conditions such as epilepsy or obsessive-compulsive disorder.

But before scientists can develop treatments that target diseases’ neural roots, they must first understand the basic workings of the 100 billion neurons and their quadrillion connections that make up the book of the brain.

Fuerst has been studying neural connections for 10 years. With support from the National Eye Institute, WWAMI Medical Education Program and UI’s Institute for Bioinformatics and Evolutionary Studies (IBEST), he and his research team are contributing to the international effort to better understand the brain.

Their work zooms in on the retina: the tissue inside the eye that collects visual information and funnels it through the optic nerve to the rest of the brain. Of the 10,000 types of brain cells, about 50 are found in the retina. One of Fuerst’s projects looks in particular at cone pedicles – complex synapses where the cone photoreceptors that detect light are first wired into the brain.

“Each one is a signaling hub that acts a little like a power strip, where one electrical input gets split into a number of different channels,” Fuerst says.

Scientists understand much about retinal cells’ physiology and output, but the details of how the cells organize into the connections that create vision is almost entirely unknown, which makes the retina an ideal area for research.

Precise technology is key to understanding the connections. Fuerst has received a technology access grant that utilizes funds from two major federal projects of which UI is part: the IBEST Center of Biomedical Research Excellence and the Institutional Development Award Network of Biomedical Research Excellence, or INBRE, both of which focus on building Idaho’s biomedical research capacity.

This funding supports Fuerst’s use of a high-resolution confocal microscope and other equipment in UI’s optical imaging core facility.

“The incredible thing about these instruments is that they actually let you see inside a structure without stripping off the surface,” Fuerst says.

Typical microscopes display pieces of retina as a flat field of cells with branching dendrites and axons – the cell parts that connect at synapses. Confocal technology allows researchers to highlight cells in a rainbow of colors so they can examine the cells’ organization and trace the paths of their connections in three dimensions.

“You go from having this field of cells where you don’t know the difference to being able to see all the cells and see them interacting,” Fuerst says.

Digging in deeper, Fuerst’s team studies neural development in mouse models that imitate human diseases in order to understand what genes are involved in forming and organizing the nervous system.

“If we want to understand development, we have to understand what contributes to it,” Fuerst says. “If we want to get at the mechanisms, we need to remove the gene or put it somewhere it isn’t normally to thoroughly test what’s going on.”

Research team member Gabriel Belem de Andrade, an undergraduate exchange student visiting UI from Brazil, examines the roles proteins play in making brain connections work. Andrade’s primary study area is biotechnology, which he says relies on the type of fundamental research he does in Fuerst’s lab.

“We need to know more of the basic function before we can proceed,” he says.

Another undergraduate lab member, John Nuhn, is a UI psychology major who plans to become a doctor. With support from the INBRE Summer Fellows program, he is applying his research in Fuerst’s lab to the National Institutes of Health’s five-year Human Brain Connectome Project, which seeks to make a complete map of neural connections.

Like Fuerst, Nuhn is excited about the big-picture implications of his work at UI.

“If we’re able to start understanding the brain and the nervous system, we can more effectively treat mental illness and other diseases that affect­­­ the brain and nervous system,” he says.