Understanding The Traffic Signals In The Brain

SciWorks Radio is a production of 88.5 WFDD and SciWorks, the Science Center and Environmental Park of Forsyth County, located in Winston-Salem.

Most of us with brains understand that our body is controlled by the noodle in our noggin. Through the sciences, we know how the heart works to pump blood and how our digestive system processes food.  But Dr. Scott Soderling, associate professor of cell biology and neurobiology at Duke University, says we really don't understand how the brain works at many basic levels.  His team's work was published in a recent issue of the journal Science.

I tell my students if their car is not working and they'd like to have it fixed, they'd like to take it to a mechanic that understands everything about how it worked. And, unfortunately, for these brain disorders, we're not there yet.

My laboratory studies how the brain functions through connections between neurons called synapses. Most brain disorders, we think, are caused by problems at these connections, and we really don't understand how they work in many instances.

Dr. Soderling describes the flow of information through the brain as a series of roads between different cities.

The cities are like regions of the brain. They're important for a variety of different functions - everything from remembering where you put your keys, to processing emotions, or making mathematical calculations. And the cars are the electrical signals, and they travel along neurons within the brain that form the streets, the connections between these cities or brain regions. And as these cars are moving along these streets, they encounter these traffic signals, and these traffic signals are the connections between these neurons. And these connections tell the cars whether or not to go forward or to pause.

The “green light” go signals have been well understood since the 1970s.

The red lights – we haven't been able to isolate from the brain to understand how they work. These types of connections are incredibly small, and so to be able to actually tease out what's inside of them is really quite a challenge. And so we developed a new way that we could isolate these stop signals from the brain so we could understand what the components were.

This method, using rodents, involved binding bacterial protein to known proteins in the “red lights” as a kind of handle. They then ground the brain down to look for that handle and everything it's attached to.

And from that, we were then able to specifically purify the proteins that existed there, that make up the components of these traffic signals that cause the action potentials to pause.

This was an exciting find because it's known that, when mutated, many of the genes that form the components of the stoplights are also involved in conditions like epilepsy, autism, and intellectual disabilities.

When we're driving down the street, we wish there weren't any stoplights. But in fact, they're absolutely essential for directing the efficient flow of traffic, and in the brain it's the same way. These inhibitory connections are absolutely essential for directing the efficient flow of information, or action potentials, from one region to another. And when they don't work, we think this is actually what causes in many cases things such as epilepsy, which is too much excitation, so not enough inhibition, or things such as autism spectrum disorders. And so our hope was that, by understanding the inner workings of how these traffic lights work, we might uncover some of the mechanisms that, when they go wrong, may lead to these different types of disorders.

This gives us now new insights into how these mutations may actually cause the disease, and so this gives us the ability to not only understand, at a fundamental level, how the brain works and regulates the flow of information, but we hope will eventually lead to a better understanding of how some of these different types of brain disorders actually happen. And that's absolutely critically important if you want to repair the brain. It's very difficult to repair something if you don't really understand how it works or how it's broken.