An electrical diagram of a building shows where all the electrical wires, fixtures and components are connected to an electrical system. When a circuit is faulty, it’s easy to identify the culprit because specific lights will not work. But the human nervous system is far more complicated. It is a living network of nerves that cannot be explained by a simple diagram, with numerous checks and balances that can change to compensate for connections that do not work correctly.

Dr. Turgay Akay, an assistant professor in the Department of Medical Neuroscience at Dalhousie University, studies the intricate mechanisms of the nervous system that enable movement. His academic research journey began as a PhD student in Germany in the late 1990s, where he studied insect leg movement for his doctoral thesis. After a short post-doctoral training in the laboratory of Dr. Michael Nusbaum at the University of Pennsylvania, he moved to the University of Alberta, in Edmonton, Alberta in 2004. Here, he continued to study leg movement in animal models in the physiology lab of Dr. Keir Pearson as a postdoctoral research fellow.

“My connection with ALS research began when I was recruited in 2007 by Dr. Thomas Jessell at Columbia University in New York to study motor neuron biology in mice that had been genetically altered. During this time I became more and more interested in the phenomenon that animals can walk almost normally despite significant loss of motor neurons, such as in ALS” said Dr. Akay. “I became an associate research scientist at the Columbia University Motor Neuron Center in 2012 and further developed my research methods. In 2014, I moved back to Canada to continue my research at Dalhousie University in Halifax, Nova Scotia.” Dr. Akay is a member of the Brain Repair Centre co-founded by collaborating scientists and clinicians at Dalhousie University and the Atlantic Mobility Action Project.

To understand how the nervous system enables movement, Dr. Akay is studying cholinergic-boutons (C-boutons), specialized synapses that are connected to motor neurons. They were first identified over 40 years ago, but their function was not known until 2009 when Dr. Akay helped identify their function in experiments using mice. He discovered that C-boutons were responsible for changing the excitability of motor neurons and that the level of excitability depended on what the mice were doing. “With swimming, motor neurons are significantly more excited and produce higher muscle activation than with walking,” Dr. Akay explained. “Similar to how a volume dial on a radio controls sound output, C-boutons can “turn up the volume” to control how motor neurons respond.”

In his work with ALS mice, he has found that they can still move quite well despite a significant loss of motor neurons. He thinks that changes in C-bouton activity are responsible for this effect. With his ALS Canada Research Project Grant of $125,000, Dr. Akay will study mice to see if and how C-bouton activity plays a role in ALS in three areas:

  1. He will examine how changes in C-bouton activity are affected during ALS disease progression.
  2. He will investigate whether neurons affected by the C-boutons are more active during ALS by comparing the changes in ALS mice with healthy mice.
  3. He will determine whether the altered excitability of C-boutons is helpful or harmful as the disease progresses.

Dr. Akay’s findings may help to explain why ALS progresses so far before changes are noticeable. C-boutons activation may compensate for motor neuron degeneration like plugging in another power source to keep them working properly.

“I hope my research will provide insights that can improve the quality of life for people living with ALS by improving their mobility and possibly slowing disease progression,” said Dr. Akay. “Whether I discover if the variation in C-bouton excitability is helpful or harmful as ALS progresses, that learning could pave the way for future research to develop a drug that could either enhance or silence C-bouton excitement and keep motor neurons functioning better for a longer time.”

This research project is one of 12 funded by the ALS Canada Research Program in 2017 following a rigorous scientific assessment by panels of global ALS experts. The panelists evaluated a larger pool of applications to identify the projects that are grounded in scientific excellence and have the potential to most quickly advance the field of ALS research in order to develop effective treatments.

ALS Canada is a registered charity that receives no government funding. Everything we do – from funding research to providing community based support for people living with ALS – is possible only because of donor generosity and partnerships with provincial ALS Societies who contribute to the ALS Canada Research Program.

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Posted in: Research