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Dopaminergic modulation of stroke recovery

Principal Investigator:
  • Christian Ethier, Université Laval
  • The Azrieli Foundation

Project Overview

Strokes often cause brain damage that affects normal cognitive and sensorimotor functions. The brain has the extraordinary ability to adapt by forming new circuits which can, to some extent, compensate for neuronal loss. The recovery of motor function can be improved by rehabilitation exercises aimed at strengthening the brain and spinal cord motor circuits. However, stroke recovery is often slow and incomplete.

Dopaminergic neurons of the midbrain are often associated to pleasure and rewards. These neurons normally release a burst of dopamine in order to indicate that ‘something good’ just happened, a signal which drives changes throughout the brain, reinforcing previously active circuits to increase the likelihood that this ‘something good’ reoccurs.

We hypothesize that dopaminergic signals have a strong potential to drive changes in the brain and spinal cord motor circuits and that they can be leveraged to improve motor recovery after stroke. We propose an experiment in laboratory rats to test whether the stimulation of dopamine neurons during rehabilitation exercises can enhance brain repair. To achieve this, we will train rats to a knob rotation task known to sensitively measure fine forelimb motor function. After subjecting rats to a controlled stroke, stimulation of dopamine neurons will be applied immediately after motor actions which are incrementally better than average. This may activate the natural signal controlling the brain adaptation and reinforce useful motor circuits responsible for that action.

We expect that this precisely timed dopaminergic stimulation will greatly accelerate and improve motor recovery beyond what is possible with physical training alone. In addition to motor function, we will examine whether stimulation of dopamine neurons increased the number of descending motor connections between the brain and the muscles. Our results will provide a novel understanding of the role of dopamine in brain repair and have direct implications for rehabilitation.