Ph.D., University of Iowa, 1991
We study the cellular and genetic underpinnings of learning and memory, using the fruit fly as a model. Our research has led to the discovery of why we remember more when we pause between attempts to “cram” new material. We also study how to reverse the process of forgetting, with an eye to developing treatments for Alzheimer’s disease.
Yi Zhong’s lab studies the neural basis of learning and memory. The team works with fruit fly models to study genes involved in human cognitive disorders, including neurofibromatosis, Noonan syndrome (NS), and Alzheimer’s disease. Mutations leading to a lack of function of the neurofi - bromatosis 1 (NF1) gene cause noncancerous tumors of the peripheral nervous system as well as learning defects. The lab’s analyses of Drosophila NF1 mutants have revealed how expression of the mutant gene affects a pathway crucial for learning and memory formation. The NF1 gene and a gene called corkscrew, implicated in NS, share a biochemical pathway. Recently, the lab succeeded in linking changes in this pathway due to specific genetic defects in NS with long-term memory deficiencies. In fly models, they discovered the molecular underpinnings of the “spacing effect”— the fact that memory is improved when learning sessions are spaced out between rest intervals. Zhong’s team also has succeeded in reversing memory deficits in mutant flies, work suggesting longer resting intervals for NS patients might reverse their memory deficits. They also identified a means of reversing memory loss in fruit flies while suppressing brain plaques similar to those implicated in Alzheimer’s disease by blocking epidermal growth factor receptor (EGFR) signaling, a pathway commonly targeted in cancer. Separately, having discovered that memory decay is an active process, regulated by the Rac protein, the team has proposed that Rac’s role in erasing memory is related to its influence on downstream cytoskeleton remodeling agents. This year, the Zhong lab explored how neurons control our response to different scents, offering insight into how the brain distinguishes between food odors that are attractive and repulsive. They discovered that neurons expressing a particular peptide were only activated by food odors, and the amount of activation predicted how much a fly was attracted to a particular odor.
Shuai, Y.C., Lu, B.Y., Hu, Y., Wang, L.Z., Sun, K., and Zhong, Y. 2010. Forgetting is regulated through Rac activity in Drosophila. Cell 140: 579–589.
Pagani, M.R., Oishi, K., Gelb, B.D., and Zhong, Y. 2009. The phosphatase SHP2 regulates the spacing effect for long-term memory induction. Cell 139: 86-98.
Wang, Y., Guo, H.-F., Pologruto, T.A., Hannan, F., Hakker, I., Svoboda, K., and Zhong, Y. 2004. Stereotyped odor representation in the mushroom body of Drosophila revealed by GFP-based Ca2+ imaging. J. Neurosci. 24: 6507–6514 Iijima, K., Liu, H.-P., Chiang, A.-S., Konsolaki, M., and Zhong, Y. 2004. Dissecting the pathological effects of human Aβ40 and Aβ42 in Drosophila: A potential model for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101: 6623–6628.
Guo, H.-F., Tong, J., Hannan, F., Luo, L., and Zhong, Y. 2000. A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. Nature 403: 895–898.
Study shows how neurons enable us to know smells we like and dislike, whether to approach or retreat
Scientists reverse Alzheimer’s-like memory loss in animal models by blocking EGFR signaling
CSHL neuroscientists reverse Alzheimer’s-like memory loss by targeting signaling protein in fruitflies
CSHL neuroscientist discovers protein that regulates forgetting of short-term memories