The research program in my laboratory is mouse behavioral genetics. The long-term goal for this program is to understand the roles of genes in cognitive processes such as learning and memory and in the pathogenesis of certain brain diseases with memory deficits. We are currently employing mouse genetic, molecular and cellular, electrophysiological (collaborating with our colleagues), immunohistochemical, and mouse behavioral approaches in our studies. 

By employing our established conditional gene manipulation systems (Cre/loxP recombination and tTA/tetO inducible/reversible gene expression systems) as well as our newly developed inducible/reversible knockout/knock-in systems, we are currently exploring the question of how memory is encoded in the brain. We are focusing on (1) how acquired information in the hippocampus is processed in the brain for long-term storage; (2) what the role is of brain regional neuronal activities in this process; (3) what the significance is of protein synthesis in this process; and (4) what the significance is of newly generated neurons in the brain in terms of memory formation. We are particularly interested in determining the roles of certain molecules in this process, including neurotransmitter systems (such as NMDA receptors and AMPA receptors), neurotrophic factors (such as BDNF), transcriptional factors (such as CREB and Arc), and protein kinase (such as CaMK-II and CaMK-IV).  

In addition, to investigate the molecular and cellular mechanisms underlying learning and memory deficits observed in certain mental disease such as schizophrenia as well as neurodegenerative disease such as Alzheimer’s disease is another major focus in this laboratory. We are particularly interested in modeling these diseases in the mouse with our conditional gene manipulation techniques and in determining the roles of gene(s) or gene mutations in the pathogenesis of these diseases. Various molecules, including NMDA receptors, BDNF, CCK-2, and presenilin etc. are currently our focus. 

More than ten projects are currently carried out in this laboratory and we believe that our projects represent state-of-the-art research in the fields of mouse behavioral genetics, neurobiology of learning and memory, and modeling of mental and neurodegenerative diseases in the mouse.  Any students or post-doctors who are interested in our research program are encouraged to contact the PI to discuss any aspects about our research. 

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References

1. Tang, Y.-P., Shimizu, E., Dube, G., Rampon, C., Keercher, G., Zhou, M., Liu, G. and Tsien, J.Z. (1999) Genetic enhancement of learning and memory in mice. Nature 401: 63-69. 2.  Tang, Y.-P.*, Rampon, C.*, Goodhouse, J., Shimizu, E., Kyin, M. and Tsien, J.Z. (2000)  Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. Nat Neurosci 3: 238-244. 3. Rampon, C., Jiang, C.H., Dong, H., Tang, Y.-P., Lockhart, D.J., Schultz, P.G.,  Tsien, J.Z. and Hu, Y.  (2000)  Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 97: 12880-12884. 4. Tang, Y.-P.*, Shimizu, E.*, Rampon, C. and Tsien, J.Z. (2000)  NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290:1170-4. 5. Tang, Y.-P., Shimizu E, Tsien J.Z. (2001)  Do 'smart' mice feel more pain, or are they just better learners? Nat Neurosci 4:453-454. 6. Feng, R., Rampon, C., Tang, Y.-P., Shrom, D., Jin, J., Kyin, M., Sopher, B., Miller, M.W., Ware, C.B., Martin, G.M., Kim, S.H., Langdon, R.B., Sisodia, S.S., Tsien, J.Z. (2001)  Deficient neurogenesis in presenilin-1 forebrain knockout mice prevents clearance of hippocampal memory traces. Neuron 32: 911-926. 7. Tang, Y.-P., Gershon E.L. (2002)  Genetic studies in Alzheimer’s disease (review). Dialo Clin Neurosci 4:139-148.  * these authors contributed equally to this work.