Picower Professor of Biology and Neuroscience Susumu Tonegawa

Susumu Tonegawa

Picower Professor of Biology and Neuroscience
Investigator in The Picower Institute for Learning and Memory
Director, RIKEN-MIT Center for Neural Circuit Genetics
Professor, Department of Brain and Cognitive Sciences
Professor, Department of Biology
Massachusetts Institute of Technology

Contact Info

Administrative Assistant

Mackenzie Abbott

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.

Because much of the fundamental processes of and neuronal mechanisms for memory are expected to be shared among mammals, and a vastly greater variety of experimental procedures is available for rodents than humans, we use laboratory mice as the primary model for memory research. With mice or other animals, memory can be monitored only through the behaviors. Thus, it is inevitable that we use a whole, live animal. At the same time, researchers must identify the crucial events and processes that are ongoing inside the brain, permitting the specific and diverse aspects of learning and memory. This latter task is the challenge for memory researchers and neuroscientists in general because the brains of higher organisms are incredibly complex—organized in a multilayer of complexity, from tens of thousands of molecules, to thousands of different types of cells, to hundreds of functionally and structurally distinct cellular assemblies, and extensive yet specific networkings of these assemblies.

In order to meet this challenge, we employ highly specific genetic manipulation techniques, creating mutant mouse strains in which a specific gene, and hence its gene product, such as neurotransmitter receptors and enzymes, is deleted or inactivated only in a specific type of cell (spatial restriction) and/or a specific period of a behaviorally defined learning or memory process (temporal restriction). Alternatively, the gene encoding the tetnus toxin can be introduced to a specific type of cell and activated in a temporally controllable manner to block a neural signal transmission. This technique, generally called the conditional transgenic method, can be accomplished by micro-manipulating mouse eggs or embryos using the site specific recombination system, Cre-loxP, and the tetracycline-controlled transcriptional system, tTA-Otet. Virus vector (AAV, Lenti, HSV, etc.)-mediated genetic manipulation can be combined with these conditional transgenic methods. Further, the recently invented optogenetic methods—including those based on the channel rhodopsin and halorhodopsin, which activate and inactivate neurons, respectively, at a millisecond timescale—can be combined with the Cre-loxP system to rapidly manipulate neural transmission in a specific cellular circuit. We then subject these genetically engineered mouse strains along with the standard strain (called control mice) to a variety of analytical methods in order to detect the effect of the genetic manipulation (called phenotype detection). These methods include behavioral tasks (for example, maze and conditioning), recordings of cellular activities via single and multiple electrodes (in vivo electrophysiology with tetrodes and EEG) surgically implanted into a specific area of the brain, recordings of transmission at specific synapses of brain slices or cultured neurons (in vitro electrophysiology by field and patch clamp recordings), in vivo and in vitro optical imaging (with confocal and two-photon microscopy), and molecular and cellular biology. The abnormality one may observe in the genetically altered mouse strains in comparison with the control mice could be a deficiency or augmentation of a particular activity (phenotype). The phenotype observed at various levels of organizational complexities and associated specifically with the known genetic manipulation of the mutant will be very informative in our understanding the brain mechanisms subserving its behavior and cognition.

Currently Ongoing and Near-Future Research Projects

We continue to study the roles of hippocampal circuits in various aspects of hippocampal memory using the multi-facet approaches described above. In addition, our research interest extends into several other brain areas that communicate with the hippocampus through specific circuits and neuromodulators. These extended studies will allow us to investigate not only the basic functions of hippocampal circuits in learning and memory, but their modulations by reward, penalty, attention and emotion, as well as the role of learning and memory in decision-making, and vice-versa.

Our research projects include studying the:

  • Role of the direct EC→CA1 pathway in hippocampal learning and memory, and memory consolidation.
  • Role of mossy fiber input from dentate gyrus granule cells in pattern completion and separation.
  • Interaction of the trisynaptic and monosynaptic pathways, as well as subcortical pathways in novelty detection and novelty-triggered learning.
  • Localization, visualization and manipulation of memory engrams through the combined use of transgenic and optogenetic methods, such as channelrhodopsin and halorhodopsin.
  • Mechanism for memory reconsolidation and extinction at the memory engram level.
  • Role of protein-synthesis dependent LTP in memory consolidation.
  • Roles of “preplay” in learning and “replay” in memory consolidation.
  • Role of specific neural circuits involving neuromodulators (dopamine, serotonin and norepinephrine) in learning and memory, decision-making and control of behaviors.
  • Role of PAK1 biochemical pathway in fragile X mental retardation.

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 Professor of Biology at MIT and a member of the Center for Cancer Research. In 1994, he founded the Center for Learning and Memory at MIT and, and, in 2002, the Picower Institute for Learning and Memory.

  • The Cloetta Prize of Foundation Professor Dr. Max Cloetta, Switzerland
  • Warren Triennial Prize of the Massachusetts General Hospital, U.S.A.
  • Genetics Grand Prize of Genetics Promotion Foundation, Japan
  • Avery Landsteiner Prize of the Gesselshat für Immunologie, West Germany
  • Asahi Prize of Asahi-Shimbun (Asahi Press), Tokyo, Japan
  • Louisa Gross Horwitz Prize of Columbia University, New York, U.S.A.
  • The V.D. Mattia Award of the Roch Institute of Molecular Biology, Nutley, U.S.A.
  • Gairdner Foundation International Awards of the Gairdner Foundation, Toronto, Canada
  • Person of Cultural Merit “Bunkakorosha” of the Japanese Government
  • Order of Culture “Bunkakunsho” from the Emperor of Japan
  • Bristol-Myers Award for Distinguished Achievement in Cancer Research
  • Robert Koch Prize of the Robert Koch Foundation, West Germany
  • Albert and Mary Lasker Award, New York City
  • The NOBEL PRIZE in Physiology or Medicine, Stockholm, Sweden
Featured publications are below. For a full list visit the lab website linked above.

April 4, 2022
Dheeraj S Roy, Young-Gyun Park, Sachie K Ogawa, Jae H Cho, Heejin Choi, Lee Kamensky, Jared Martin, Kwanghun Chung, Susumu Tonegawa. Nature Communications volume 13, Article number: 1799 (2022)
August 17, 2017
Roy DS, Kitamura T, Okuyama T, Ogawa SK, Sun C, Obata Y, Yoshiki A, Tonegawa S. Cell. 2017 Jul 29. pii: S0092-8674(17)30820-6. doi: 10.1016/j.cell.2017.07.013. [Epub ahead of print]
April 7, 2017
Kitamura, T.*, Ogawa, S.K.*, Roy, D.S.*, Okuyama, T., Morrissey, M., Smith, L.S., Redondo, R.L., Tonegawa, S., Science 356: 73-78 (2017).
October 17, 2016
Kim, J, Pignatelli, M, Xu, S, Itohara, S, Tonegawa, S. 2016. Nat. Neurosci. 19, 1636-1646.
March 16, 2016
Roy, DS, Arons, A, Mitchell, TI, Pignatelli, M, Ryan, TJ, Tonegawa, S. 2016. Nature 531, 508-12.

When a task adds more steps, this circuit helps you notice

August 5, 2022
Research Findings
By tracking feedback during tasks, the anterior cingulate cortex notices when a new step has become necessary and signals the motor cortex to adjust

A single memory is stored across many connected brain regions

April 11, 2022
Research Findings
Innovative brain-wide mapping study shows that “engrams,” the ensembles of neurons encoding a memory, are widely distributed, including among regions not previously realized

'What Were you Thinking?'

September 20, 2021
Research Feature
How brain circuits integrate many sources of context to flexibly guide behavior

Neuroscientists identify brain circuit that encodes timing of events

January 11, 2021
Research Findings
Findings suggest this hippocampal circuit helps us to maintain our timeline of memories.

Scientists identify specific brain region and circuits controlling attention

November 2, 2020
Research Findings
Study shows that norepinephrine producing neurons in the locus coeruleus produce attention focus, impulse control via two distinct connections to prefrontal cortex

From Biological Intelligence to Artificial Intelligence

September 17, 2020
Research Feature
How basic neuroscience research by Picower faculty has mattered to AI

Neuroscientists find memory cells that help us interpret new situations

April 6, 2020
Research Findings
Neurons that store abstract representations of past experiences are activated when a new, similar event takes place

With these neurons, extinguishing fear is its own reward

January 15, 2020
Research findings
The same neurons responsible for encoding reward also form new memories to suppress fearful ones

Engrams emerging as the basic unit of memory

January 2, 2020
Research Findings
Review in Science traces progress in studying the neural substrate for storing memories

Memory and its meaning

October 7, 2019
News Feature
25 Years of Picower Institute research

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