Grant: Project Grant

Stroke is the leading cause of adult disability and the third leading cause of death in Canada. In addition to having potentially devastating effects on quality of life, stroke is estimated to cost the Canadian economy more than $3.6 billion a year in treatment, physician services, hospital costs, lost wages, and decreased productivity (Statistics Canada, 2012). The primary motor cortex in the brain is responsible for voluntary movement. It has also been proposed to be one of the sites for motor memory formation and storage, also known as motor representations. Therefore, when the motor cortex is damaged following a stroke, we lose the ability to execute movements that were formerly part of normal daily life. One hypothesis to achieve true recovery is to re-initiate motor learning in the brain and establish new representation to replace the destroyed ones (Murphy and Corbett, 2009). Hence, a determination of the basic molecular mechanisms underlying motor learning will enhance our understanding of post-traumatic rehabilitation in brain injury and disease. Our lab has developed a novel forelimb lever-press task for head-fixed mice, permitting us to perform chronic two-photon imaging and follow learning-related dynamic changes among various neuron subtypes in the motor cortex of behaving mice over weeks of training. Here, we propose a series of experiments employing in vivo two-photon imaging combined with the lever-press task to elucidate the molecular mechanisms underlying learning-driven inhibitory neural circuit modifications essential for the structural and functional plasticity with motor memory formation in the awake brain. By deciphering the basic mechanisms underlying motor movement acquisition in normal heathy brains, our work will have immense potential to understand dysfunction in circuits altered by stroke and aid in the development of novel therapeutic targets for stroke recovery and other brain injuries impairing motor function