Grant: Project Grant

Stroke is the leading cause of adult disability in North America, often robbing its victims of the ability to perform even the most basic sensory-motor tasks (dressing, eating, brushing teeth, driving) that we take for granted in daily life. Since many patients fail to recover adequately with existing treatment options, there is a great need to develop a deeper understanding of what happens to sensory circuits after stroke and use this knowledge to develop new treatments that will maximize recovery. One brain region that plays a crucial role in processing sensory information is the thalamus. After stroke, it is thought that the connections from this region are either damaged or are dysfunctional thereby disrupting how our brain processes sensory information. Surprisingly little is known about what happens to these connections after stroke and to what extent can they recover normal function. The first goal of this research project will be to use imaging technologies to assess the structure and functionality of thalamic connections after stroke. Since our preliminary data suggest that stroke does indeed make these connections less excitable, we will then use a powerful new experimental approach to promote the excitability of these connections. This approach involves genetically modifying cells to make them more excitable by expressing proteins (derived from algae) that can be activated by light (called "optogenetics"). We will then determine the impact of optogenetic stimulation on neural circuit rewiring and recovery of sensorimotor function. And finally, since we have pilot data proving the feasibility and utility of this experimental stroke therapy, we will explore what molecular mechanisms mediate its beneficial effects. Ultimately, the proposed project will generate critical foundational data regarding the effects of stroke on sensory circuits and will test a new therapeutic approach to improve recovery of sensori-motor function in a rodent model of stroke.