- Neuroscience Institute
B.Sc., Cell biology and genetics, 2000, University of British Columbia
Ph.D., Neuroscience, 2006, University of British Columbia
Postdoctoral fellowship, 2012, University of California, San Diego
Our lab is interested in understanding how blood is supplied to the brain during health and disease. We use advanced optical techniques and genetic targeting strategies to visualize and manipulate blood flow at the level of the smallest arterioles, venules and capillaries of the brain. The goal is to determine how anomalies in blood flow at the microvascular level affect brain function and repair after injury. Our current research is driven by three main questions.
1) What microvascular changes occur in the chronic stages of stroke, and how do those changes affect neuronal rewiring during rehabilitation?
2) What vascular dysfunctions are involved in cognitive impairment during dementia, and can we advance imaging techniques to detect them in humans?
3) How is cortical blood flow is regulated by the electrical, ionic and modulatory activity of the underlying neurons and nonneuronal cells?
Our research is expected to advance our understanding and treatment of vascular diseases in human subjects including stroke and vascular dementia. It is also expected to impact measurement of brain function and detection of microvascular lesions by non-invasive imaging techniques such as MRI.
The smallest stroke: Occlusion of one penetrating vessel leads to microinfarction and a cognitive deficit. A.Y. Shih, P. Blinder, B. Friedman, P.S. Tsai, G.M. Stanley, P.D. Lyden, D. Kleinfeld (2012). Nature Neuroscience. 16(1):55-63.
Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. Schaffer, D. Kleinfeld (2012). Journal of Cerebral Blood Flow and Metabolism. 32: 1277-1309.
Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. P.J. Drew, A.Y. Shih, D. Kleinfeld (2011). Proceedings of the National Academy of Sciences. 108(20): 8473-98.
A guide to delineate the logic of neurovascular signaling in the brain. D. Kleinfeld, P. Blinder, P. J. Drew, J.D. Driscoll, A. Muller, P.S. Tsai, A.Y. Shih. (2011) Frontiers in Neuroenergetics. 2011. 3:1.
Topological basis for the robust distribution of blood to rodent neocortex. P. Blinder *, A.Y. Shih *, C.A. Rafie, and D. Kleinfeld (2010). Proceedings of the National Academy of Sciences. 107(28): 12670-5. (* equal co-first authors).
Chronic optical access through a polished and reinforced thinned skull. P.J. Drew, A.Y. Shih, P.S. Tsai, P. Knutsen, D. Davalos, P. Blinder, K. Akassoglou, and D. Kleinfeld (2010). Nature Methods. 7(12): 981-4.
Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke. A. Y. Shih, B. Friedman, P. J. Drew, P. S. Tsai, P. D. Lyden and D. Kleinfeld (2009). Journal of Cerebral Blood Flow and Metabolism. 29: 738-751.