Learning and memory is vital for our normal day-to-day living, whether it is to go home, to play tennis, or simply to make a cohesive speech. Many of us have personally witnessed the devastating consequences of memory disorders such as Alzheimer's and Parkinson's diseases. Our laboratory's main research interest is to understand the molecular, cellular, neuronal circuitry, and neural systems mechanisms underlying learning and memory and associated cognitive functions.

Our main approach is to generate conditionally engineered mouse strains in which a specific gene or its protein function is eliminated in a spatially restricted and/or temporally reversible manner in the brain and analyze these mice with a series of techniques designed to detect abnormal phenotypes at different levels of complexity from molecules and cells to neuronal circuitries and brain systems to behavior of a whole living animal. These techniques include those of molecular and cell biology, histology and histochemistry, confocal and two-photon laser microscopy, in vitro and in vivo electrophysiology, and behavioral studies. Our goal is to identify a correlate at a particular level of complexity of an event occurring at another level, and eventually establish their cause-consequence relationship from molecules all the way to behavior. As research targets, we have thus far focused on hippocampus-dependent memory, i.e., memory of events, facts, space, etc. The hippocampus consists of multiple interconnected areas such as area CA1, CA3, and dentate gyrus (DG), each of which contains a unique set of neurons composing a distinct cellular network. Our effort is directed toward identification of the roles of specific proteins (e.g., NMDA receptors), synaptic plasticity and neural circuitries in each of these areas in different stages of the mnemonic process such as memory acquisition, consolidation, and recall. We are also investigating the distinct role of each of these factors in different types of memory, such as episodic vs. reference memory. In the near future, we will expand the research target to areas outside the hippocampus such as the prefrontal cortex and striatum in order to investigate the roles of these brain areas and their molecules in modulating certain types of learning and memory.

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Mutant mouse with memory recall deficit. The coincidence of the mountain peak with the location of the platform (indicated by the black circle) on the right panel shows that normal mice can recall the memory of a specific space while the lack of the coincidence on the left panel shows that CA3-restricted NMDA receptor knockout mice cannot recall this memory under the same circumstances.

Picower Professor of Biology and Neuroscience, Departments of Biology and Brain and Cognitive Sciences Director, Picower Center for Learning and Memory
Investigator, Howard Hughes Medical Institute
Investigator, and Director of the RIKEN-MIT Neuroscience Research Center

Susumu Tonegawa received his Ph.D. in Molecular Biology from the University of California, San Diego. After postdoctoral training at the Salk Institute, he joined the Basel Institute for Immunology. In 1981, he was appointed as Professor of Biology at MIT and a member of the Center for Cancer Research. In 1994, he founded the Picower Center for Learning and Memory at MIT. He is a recipient of the Louisa Gross Horwitz Prize, the Gairdner Foundation International Award, Order of Culture "Bunkakunsho" from the Emperor of Japan, Bristol Myers Squibb Prize in Cancer Research, the Albert and Mary Lasker Award, and the 1987 Nobel Prize in Physiology or Medicine.