New light shed on how brain signals connect to neurons

Supercomputers have been employed to generate an atomic scale map which records how glutamate, the signalling chemical, binds to a neuron in the brain.

As one neuron releases glutamate, an adjacent neuron latches onto the chemical through a structure on the neuron’s surface called a receptor. The glutamate-receptor connection triggers a neuron to open chemical channels that let in charged particles called ions, creating an electric spark that activates the neuron.

The results of this tracking reveal more about the dynamic physics of the chemical’s pathway and the speed of nerve cell communications.

 

 

All of this happens within a millisecond, and what hasn’t been known is the way receptors latch onto glutamate. Our new experiments suggest that glutamate molecules need to take very particular pathways on the surface of glutamate receptors in order to fit into a pocket within the receptor.

Albert Lau, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine

The research was undertaken using ‘Anton’, the supercomputer run by the Pittsburgh Supercomputing Center, with the help of researchers from Humboldt University in Berlin who specialise in recording how charged particles flow between biological membranes.

 

 

There are many ways glutamate can connect with a receptor. But some pathways are more direct than others. The difference is like taking the faster highway route versus local roads to get to a destination. What we see is an electrostatic connection, and the path glutamate follows is determined by where the charges are. In the world of physics, when two objects near each other have opposing electrical charges, they attract each other.

Albert Lau, Ph.D

From Johns Hopkins Medicine:

Yu and Lau counted how frequently they saw glutamate in every position on the receptor. It turns out that glutamate spends most of its time gliding into three distinct pathways.

Zooming in more closely at those pathways, the scientists found that the chemical’s negatively charged atoms are guided by positively charged atoms on the neuron’s glutamate receptors.

Lau says that the positively charged residues on the glutamate receptor may have evolved to shorten the time that glutamate takes to find its binding pocket.

Then, they measured the resulting electrical currents to determine if there was a change in the rate of the receptor’s activation in the presence of glutamate.

The results of that experiment showed that mutated glutamate receptors activated at half the speed of the normal version of the receptor.

Lau says that further research is needed to determine if other compounds that target the glutamate receptor, such as quisqualic acid, which is found in the seeds of some flowering plants, tread the same three pathways that glutamate tends to follow.

So far, Lau’s team has focused its computer simulations only on the main binding region of the glutamate receptor. The researchers plan to study other areas of glutamate receptors exposed to glutamate.