University of Calgary PhD student Simon Sharples involved in breakthrough dopamine study

Ever wonder how a chicken is able to keep running around a farmyard for a moment after its head is chopped off? It all has to do with the spinal cord. Even with the head detached from the body, the spinal cord continues to play a key role in controlling our movements, particularly ones like walking. The spinal cord contains the necessary circuitry that produces movement patterns, even in absence of voluntary control.

Those circuits in the spinal cord are under the control of censors in the brain regularly, and they modify how movement is performed. This is why people, or chickens, don’t just wander aimlessly. Your brain navigates you through your environment – it is helping you adapt to the stepping patterns that the spinal cord is producing.

The origin of these signals is in the brain. They send projections, known as axons, to the lumbar spinal cord, where the movements are controlled.

When spinal cord injury occurs, those projections are cut. This results in a loss of important chemical signals, which is why people often become paralyzed after sustaining such an injury.

However, new research being conducted by Simon Sharples, a PhD student at the University of Calgary, is hoping to change how people live with spinal cord damage – by examining how dopamine works to activate networks in the spinal cord that control movement.

“The most exciting part of my job,” Sharples said, “[is] the ability to generate new ideas, and test them yourself – to see if they work, to see if they don’t. It’s exciting and surprising and frustrating. It’s continuous and constantly happening.”

Simon Sharples is conducting groundbreaking research at the University of Calgary while pursuing his PhD under supervisor Dr. Peter Whelan. Photo by Tara RathgeberSharples completed both his Bachelors and Masters of Science in kinesiology at Wilfrid Laurier University, and now, he is conducting groundbreaking research at the University of Calgary while pursuing his PhD, under supervisor Dr. Peter Whelan.

His passion for science carries over into more philanthropic areas of life as well. Sharples found time amidst all of this groundbreaking research to mentor a young high school student spending time in Dr. Whelan’s lab.

“He would spend an hour or two every day helping him to understand neuroscience. That student went on to win the Calgary Brain Bee neuroscience competition, the Canadian National Brain Bee, and even won 5th place in the International Brain Bee,” Dr. Whelan said.

Sharples’ enthusiasm for life visibly carries over into his work, particularly in one of the most recent papers he has had published, entitled: Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord.

“In the context of understanding how these chemical signals, like dopamine, could translate to humans, it’s very relevant when it comes to things like spinal cord injuries,” says Sharples. There is great potential for developing advanced forms of human therapy with the knowledge gained from this discovery, if follow up experiments are a success.

If scientists could fully understand and replicate how brain signals activate motor networks in the spinal cord, then pharmacological intervention could potentially be utilized to reactivate circuits that become damaged and dysfunctional following a spinal cord injury.

A key chemical signal in this equation is dopamine. Sharples has already discovered that dopamine plays a critical role in engaging motor circuits. Essentially, it increases the output of any given brain signal in order to help stabilize these motion patterns, which Sharples was then able to record.

This paper was born from advancing previous research that began in 2012, when he came into the Whelan Lab at the Hotchkiss Brain Institute at the University of Calgary. A previous grad student, Jen Humphries, had begun the aforementioned project as a part of her thesis, and Sharples was only required to do a few wrap up experiments to get the paper published.

“What his work has been doing is looking at the direct effects of dopamine at the level of the spinal cord in controlling movements, and that is a new way of thinking about the role of dopamine,” Dr. Whelan explained.

The chemical signal dopamine plays an integral role in engaging motor circuits in the spinal cord, Sharples has found. The key to improving the quality of life of, or even curing, victims of paralysis caused by spinal cord injury could very well be discovered upon further study of dopamine’s role in stabilizing motion patterns. Photo courtesy Wikimedia Commons, Creative CommonsBut with new ideas come new problems, and Sharples ended up with an onslaught of new questions as more and more experiments were conducted in the effort to wrap up the project.

“It just kept going and going, it involved me doing more experiments for a year and a half, if not more,” Sharples said.

This lead to Sharples being able to present some of the work he participated in at the Society for Neuroscience meeting that year, as well as engage in collaboration with Dr. Stefan Clemens at East Carolina University, delving deeper into how dopamine affects locomotion

“He was here for about six weeks doing experiments that complimented his experiment back in Calgary,” Dr. Clemens said of Sharples. “He was very forthcoming and open. He’s a very smart student and I would have loved to have him here longer, get him out of the cold of Calgary, so to speak.”

This partnership lead to the introduction of Dr. Clemens’ transgenic mouse line – which had the appropriate receptor knocked out of their biology – to Sharples’ research.

“Working in animal models, with mice, affords the opportunity to really probe how these spinal circuits, these neuronal circuits, really function – and in great detail,” Sharples added.

The pair were able to record single cells in the spinal cord that project to muscles, called motoneurons, and see how they were responding to different signals sent from the brain, such as dopamine.

It wasn’t smooth sailing for Sharples when the transgenic mouse line was introduced, however.

“You get nitty gritty issues like setting up breeding pairs in these [mice], which can be problematic at times,” he said.

While the experiments performed were all executed in vivo – in insolation – for Sharples’ paper, the future holds the promise of this project being applied in freely behaving mice if current research yields positive results.

Thumbnail courtesy of Angela Della Torre, Creative Commons

trathgeber@cjournal.ca

The editor responsible for this article is Michaela Ritchie, mritchie@cjournal.ca