Kirk Personius, PT, PhD

His research focuses on how nerve and muscle interact during development, aging and disease. Currently, he is studying the role of the nervous system in muscle atrophy and how nerve activity influences neuromuscular development.

Through this project, Personius is studying the role of motor neuron innervation in sarcopenia, the loss of muscle mass and function during aging. Muscles depend on innervation—being connected to the musculoskeletal nervous system—to maintain function. A well-studied example of a breakdown in the neuromuscular system is the muscle atrophy seen in Bell’s palsy following damage to the facial nerve. If a muscle fiber loses the connection to its nerve—it has only one—it withers.

The area that Personius is investigating is not muscle fiber, but the neuromuscular junction, the connection between the nervous system and muscle where nerve signals arrive and stimulate actions. He is looking at how the connection is maintained in working condition and whether it is failure at the connection that is the chief culprit in the loss of muscle function in sarcopenia.

Personius has shown that a particular receptor in neuromuscular junction—the tyrosine kinase B (TrkB) receptor—may be a key to a sequence of molecular events that lead to muscle atrophy. TrkB—called “track-B”—is a kind of dock for particular proteins called neurotrophins that are messengers in a repair and regulation system that keeps cells healthy and functioning. He has found that reducing the number of TrkB receptors in a neuromuscular junction by half causes changes in the junction that resemble changes caused by aging. Reducing the number of TrkB receptors leads to a spreading apart of another set of receptors that “hear” signals from the motor nerve; the function of the neuromuscular junction then starts to show fatigue, and the muscle begins to atrophy.

Personius says that practical implications from this research suggest that if a way can be found to maintain TrkB receptor quantity, that may, in turn, maintain the neuromuscular junction and the muscle fiber it controls.

“Muscle is ultimately dependent upon nervous input to function, so studying muscle independent of the nervous system is problematic,” he said. “Understanding how the neuromuscular system ages will help us to prevent loss of muscle function in senescence.”

In related research, he is looking at how the nerve-muscle system develops. When we’re born, we have multiple nerves connected to each muscle fiber; during the first few months of life, those connections are reduced to one nerve for each muscle fiber, a process called synapse elimination.  Personius has shown that the pattern and amount of nervous activity is important in this pruning process. Personius is currently working on understanding the molecular mechanisms underlying this sorting of neurological connections.

“We know that nervous activity influences which neuromuscular connections are maintained and which are permanently eliminated,” he said. “What we don’t know are the molecular mechanisms by which the muscle ‘listens’ to the nervous activity and chooses to support one connection and delete the other.  This is what we are trying to understand now.”

Personius welcomes PhD and master’s students from the rehabilitation science, neuroscience and exercise science programs, as well as undergraduate University Honors students, to his lab for research collaboration.