Learning and memory are vital for day-to-day living—from finding our way home to playing tennis to giving a cohesive speech. Some of us have personally witnessed the devastating consequences of memory disorders, whether it's the severe inability to form new memories, as seen in Alzheimer's patients, or difficulty in suppressing a recall of a memory of a highly unpleasant experience, as seen in PTSD patients. The main research interest in my laboratory is to decipher brain mechanisms subserving learning and memory. We seek to understand what happens in the brain when a memory is formed, when a fragile short-term memory is consolidated to a solid long-term memory, and when a memory formed previously is recalled on subsequent occasions. We also seek to understand the role of memory in decision-making, and how various external or internal factors, such as reward, punishment, attention and the subject's emotional state, affect learning and memory. In summary, we study how the central nervous system in the brain enables our mind, with a focus on learning and memory.
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Selected Publications
  1. Liu X., Ramirez, S., Pang, P., Puryear, C., Govindarajan, A., Deisseroth, K., and Tonegawa S. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature (2012), doi:10.1038/nature11028.
  2. Nakashiba, T., Cushman, J., Pelkey, K., Renaudineau, S., Buhl, D., McHugh, T.J., Rodriguez Barrera, V., Chittajallu, R., Iwamoto, K.S., McBain, C.J., Fanselow, M.S. and Tonegawa, S. Young Dentate Granule Cells Mediate Pattern Separation whereas Old Granule Cells Facilitate Pattern Completion. Cell 149 (1): 188-201 (2012).
  3. Suh J, Rivest AJ, Nakashiba T, Tominaga T, Tonegawa S. Entorhinal cortex layer III input to the hippocampus is crucial for temporal association memory. Science 334: 1415-2 (2011).
  4. Govindarajan, A., Israely, I., Huang, S.Y., and Tonegawa, S. The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTPNeuron 69:132-146 (2011).
  5. Dragoi, G. and Tonegawa, S. Preplay of future place cell sequences by hippocampal cellular assembliesNature 469: 397-403 (2011).
  6. Slutsky, I., Abumaria, N., Wu, L., Huang, C., Zhang, L., Li, B., Zhao, X., Govindarajan, A., Zhao, M., Zhuo, M., Tonegawa, S., and Liu, G. Enhancement of Learning and Memory by Elevating Brain MagnesiumNeuron 65:165-177 (2010).
  7. Jinde, S., Belforte, J.E., Yamamoto, J., Wilson, M.A., Tonegawa, S., and Nakazawa, K. Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell deathEuropean Journal of Neuroscience30:1036–1055 (2009).
  8. Nakashiba, T., Buhl, D.L., McHugh, T.J., and Tonegawa, S. Hippocampal CA3 Output Is Crucial for Ripple-Associated Reactivation and Consolidation of MemoryNeuron 62:781-787 (2009).
  9. Nakashiba, T., Young, J.Z., McHugh, T.J., Buhl, D.L., and Tonegawa, S. Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learningScience 319:1260-1264 (2008).
  10. Tonegawa, S., and McHugh, T.J. The ins and outs of hippocampal circuitsNeuron 57: 175-177(2008).
  11. Hayashi, M.L., Shankaranarayana Rao, B.S., Seo, J.S., Choi, H.S., Dolan, B.M., Choi, S.Y., Chattarji, S., and Tonegawa, S. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in micePNAS104:11489-11494 (2007).
  12. McHugh, T.J., Jones, M.W., Quinn, J.J., Balthasar, N., Coppari, R., Elmquist, J.K., Lowell, B.B., Fanselow, M.S., Wilson, M.A., and Tonegawa, S. Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal NetworkScience 317:94-99 (2007).
  13. Govindarajan, A., Shankarananarayana Rao, B.S., Nair, D., Trinh, M., Mawjee, N., Tonegawa, S., and Chattarji, S.Transgenic brain-derived neuroptrophic factor expression causes both anxiogenic and antidepressant effects.PNAS 103:13208-13213 (2006).
  14. Govindarajan, A., Kelleher, R.J., and Tonegawa, S. A clustered plasticity model of long-term memory engrams.Nature Reviews Neuroscience 7:575-583 (2006).
  15. Kelleher, R.J., Govindarajan, A., Jung, H.-Y., Kang, H., and Tonegawa, S. Translational control by MAPK signaling in long-term synaptic plasticity and memoryCell 116:467-479 (2004).
  16. Gerber, D.J., Hall, D., Miyakawa, T., Demars, S., Gogos, J.A., Karayiorgou, M., and Tonegawa, S. Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunitPNAS 100:8993-8998 (2003).
  17. Miyakawa, T., Leiter, L.M., Gerber, D.J., Gainetdinov, R.R., Sotnikova, T.D., Zeng, H., Caron, M.G., and Tonegawa, S. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia.PNAS 100:8987-8992 (2003).
  18. Nakazawa, K., Quirk, M.C., Chitwood, R.A., Watanabe, M., Yeckel, M.F., Sun, L.D., Kato, A., Carr, C.A., Johnston, D., Wilson, M.A., and Tonegawa, S. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297:211-218 (2002).
  19. Zeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B.D., Miyakawa, T., Bear, M.F., and Tonegawa, S.Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memoryCell 107:617-629 (2001).
  20. McHugh, T.J., Blum, K.I., Tsien, J.Z., Tonegawa, S., and Wilson, M.A. Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout miceCell 87:1339-1349. (1996).
  21. Tsien, J.Z., Huerta, P.T., and Tonegawa, S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memoryCell 87:1327-1338 (1996).
  22. Tsien, J.Z., Chen, D.F., Gerber, D., Tom, C., Mercer, E.H., Anderson, D.J., Mayford, M., Kandel, E.R., and Tonegawa, S. Subregion-and cell type-restricted gene knockout in mouse brainCell 87:1317-1326 (1996).
  23. Silva, A., Stevens, C., Tonegawa, S., and Wang, Y. Deficient Hippocampal Long-Term Potentiation in a Calcium-Calmodulin Kinase II Mutant MiceScience 257:201-206 (1992).
  24. Silva, A., Paylor, R., Wehner, J.M., and Tonegawa, S. Impaired Spatial Learning in a Calcium-Calmodulin Kinase II Mutant MiceScience 257:206-211 (1992).
  25. Tonegawa, S. The Molecules of the Immune SystemScientific American 253:122-131 (1985).
  26. Tonegawa, S. Somatic Generation of Antibody DiversityNature 302:575-581 (1983).