Grant: Foundation Grant

<html> <body> <p> <b>My overarching focus</b> is to understand how the cortex adapts after stroke, resulting in a remapping of function from damaged to surviving areas. By understanding the process at a circuit level, I hope to improve it using brain stimulation or other plasticity-inducing treatments. My lab pioneered the application of high-resolution imaging, as well as optogenetic circuit manipulation techniques, in mouse cortex <i>in vivo</i>. We study cortex because it is linked to sensory and motor actions and is accessible via less invasive, transcranial chronic imaging windows and can be a major site of stroke damage. <b>We hypothesize that</b> <b>stroke is a disorder of functional connectivity, where one region of brain is damaged and surviving areas compensate.</b> <br> <br> <b>Major questions:</b> <br> 1) How is the mouse cerebral cortex organized into macroscopic functional domains that are associated with sensory processing and forelimb movements?<br> 2) How and where does functionally relevant activity remap in mouse forelimb sensorimotor cortex after focal stroke, and how does connectivity information provide predictive value?<br> 3) How can we optimize movement-based rehabilitation to promote recovery?<br> 4) How can we optimize brain stimulation to promote recovery after stroke?<br> <br> <b>Collaborations and vision</b><b>:</b> The stroke field needs automated, quantifiable longitudinal tools for evaluating the recovery of sensory motor function in rodents. To aid stroke recovery research, we are developing an innovative mouse robotic forelimb lever-pulling paradigm in collaboration with S. Scott of Queen&rsquo;s University, who invented the KINARM robot used to study limb movements in humans. Our system enables quantification of natural forelimb movements, as well as perturbation by applying defined forces, and can be used in combination with optogenetics to test hypotheses concerning stroke recovery. High trial numbers, automation, and shared features with clinical tools (force feedback and ability to produce passive movements) facilitate evaluation of pilot treatments for patients. A second version will provide self-directed continuous (24/7) assessment and optogenetic manipulation for 5 mice at a time in home cages.<br> <br> <b>How results advance knowledge and health care in the short- and long-term</b><b>:</b> Using mouse models with optogenetics (to monitor circuits through recombinant activity sensors and actuators that permit circuit manipulation), we causally study sensory-motor circuits in real time. We hope to better understand long-range cortical circuits in mouse and to use this information to aid &ldquo;circuit-based&rdquo; treatments that enhance permissive surviving circuits, or inhibit potentially detrimental ones. These findings can be translated to human by making analogies between connectional structure-function and rules for stimulation-based, plasticity-enabling treatments.<br> <br> <b>Expertise and experience:</b> The niche of my lab is mouse cortical high-speed imaging and circuit manipulation tools to study interactions between cortical areas in chronic models of human disease.<br> <br> <b>Mentoring/training activities:</b> Students are part of the UBC Grad Program in Neuroscience and are supported by national training organizations that I contribute to including the Canadian Partnership for Stroke Recovery and the Canadian Neurophotonics Platform. The lab expertise in optical hardware, image analysis/acquisition software, and neurophysiology provides specialized training and enables discovery by providing balance between method execution and creativity.</p> </body> </html>