Neurobiologist Gerald Downes, with chemist James Chambers at the University of Massachusetts Amherst and Amherst College neurobiologist Josef Trapani, have been awarded a three-year $824,025 collaborative research grant from the National Science Foundation to study the zebrafish brain to better understand how neurons regulate locomotion.

Downes, the lead investigator, says his ultimate research goal is to better understand how different chemical signals, called neurotransmitters, work together at cellular and molecular levels to coordinate normal locomotion such as walking and swimming.

Downes says the grant will also support his plan to bring neuroscience demonstrations to as many as 600 Springfield and Holyoke charter middle and high school students in their science classes beginning in spring 2016, followed by visits to UMass Amherst. Participating schools include the Renaissance Charter School in Springfield and Paolo Frieri Social Justice High School in Holyoke.

"This is an important aspect of the grant to me," he says. "I believe in reaching out to young students, particularly from disadvantaged backgrounds, to show them who scientists are and what we do. Hopefully we will help inspire some students to pursue careers in science."

As the neurobiologist explains, locomotion is possible because brain cells, or neurons, communicate with each other using the neurotransmitters. In the brain's neuronal networks, signals pass from one neuron to another, then to neurons in the spinal cord, which finally pass signals to muscles.

"Some neurotransmitters increase neuron activity whereas others decrease neuron activity. We're working to tease out cellular and molecular mechanisms of brain circuitry that control movement," he adds. "And because there are many similarities in neurotransmitters and locomotor networks between zebrafish and mammals, this work can have implications about locomotion in many species, including humans."

Zebrafish have a more simple brain and spinal cord than mammals and their embryos are transparent, which makes them easy to examine under a microscope, the neurobiologist points out. For this project the researchers will focus on how one neurotransmitter known as gamma aminobutyric acid type A (GABA) regulates locomotor networks in the brain.

Downes explains, "Part of the difficulty in understanding how these neuronal networks function is that there are so many different GABA receptors, which allow neurons to receive GABA signals. So a main goal of this project is to identify individual types of GABA receptors that are important for locomotion."

To accomplish this, the team will use a variety of approaches involving the mutation of different GABA receptors and examining the effects such mutations have on locomotion. Trapani's lab will investigate how mutations change the electrical activity of individual neurons involved in locomotion, for example.

In addition, the team will use drugs developed by Chambers that bind to GABA receptors and block their function depending on the wavelength of light. GABA binding to a receptor can be blocked using one wavelength of light, but not using a different one, Downes explains. The transparency of the zebrafish embryo makes them great for this optical approach, he adds.

"Using light, we will be able to turn on and turn off different types of GABA receptors on different cell types," Downes says, "and see how that effects locomotion." "We're thrilled to bring together our different areas of expertise to tackle such a complex but interesting problem. With all of the new technology now available, it's a great time to be a neuroscientist."

The project also includes a training element that will support UMass Amherst alumna Kelly Anne McKeown, assistant professor of biology at Westfield State University, and two of her students to conduct summer research in neuroscience using state-of-the-art laboratory instruments and techniques in the Downes lab.