My PD Story

Deciphering gait signaling to improve movement therapies

The metaphor of “a walk in the park” implies that something is simple and easy; however, the neuroscience involved in such an activity is incredibly complex and relatively unstudied. This complexity is most evident in the context of movement disorders such as Parkinson’s disease (PD), where current therapies struggle to address the movement issues associated with the condition. Rodrigo Manuel Paz, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, has homed in on a specific region of the brain crucial for walking and will be devoting his research to better understanding how it works and how novel therapies can better treat trouble moving or walking in people with PD.

Dr. Paz is particularly interested in the brain’s way of managing gait, the repeating pattern of coordinated muscle activity associated with walking. In PD, gait impairment leads to loss of balance and risk of falling, as the brain struggles to maintain a consistent walking rhythm.

Working alongside his mentor, Dr. Alexandra Nelson at University of California San Francisco, Dr. Paz plans to investigate how gait may be regulated by the motor thalamus region of the brain. The motor thalamus receives signals from the basal ganglia, a neuron hub which contains the dopamine neurons that are lost in PD, and relays those signals to the motor cortex, which ultimately communicates the movement command to the muscles.

Dr. Paz will use mice in his experiments, comparing those with PD-like neurodegeneration to those without such neuron loss. A device will be attached to the mice that allows Dr. Paz to measure the activation of motor thalamus neurons as the mice walk freely, while high-speed cameras capture and correlate those activations to their gait. These data will provide insight into how the motor thalamus neuron activity may connect to walking coordination and whether such activity is impaired in PD-like mice, contributing to movement dysfunction.

Next, Dr. Paz will use brain slices from mice with and without PD-like neurodegeneration to better understand the mechanistic changes that may be occurring between the motor thalamus and its associated brain regions. Using optogenetics — a technique by which light can be used to trigger genetically-altered cells — he will stimulate neurons from the basal ganglia and motor cortex to watch and calculate motor thalamus responses and determine how neurodegeneration affects that important communication pathway in the brain.

Dr. Paz is enthusiastic about what such results may mean for future therapies. “By understanding how motor thalamus influences gait and how changes in synaptic inputs drive impaired gait signals in motor thalamus, this project will establish a fundamental framework for improving therapies specifically aimed at alleviating gait deficits in people with PD,” he said.

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