Centers & Labs

RIKEN Brain Science Institute

RIKEN-MIT Center for Neural Circuit Genetics (CNCG)

Laboratory Head: Susumu Tonegawa (Ph.D.)
Susumu  Tonegawa(Ph.D.)

Learning and memory are vital for day-to-day life—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 inability to form new memories, as in Alzheimer’s disease patients, or the difficulty in controlling memory associations, as can be seen in depression or PTSD; learning and memory disorders are common underlying factors in many of the age-related and behavioral diseases we face today. The main research interest in my laboratory is to decipher brain mechanisms subserving learning and memory. We examine what happens in the brain when a memory is formed, when a fragile short-term memory is consolidated to a stable long-term memory, when a long-term memory formed previously is recalled on subsequent occasions, and how different brain areas affect and control these dynamic processes. In summary, we study how the function of the brain, its subregions, and interconnections (neural circuits) enable the human mind, in healthy and disease states, with a focus on learning and memory.

Because much of the fundamental processes and neuronal mechanisms of memory are conserved across mammalian species, and a vastly greater variety of experimental procedures are available for rodents than human subjects, we use laboratory mice as the primary model for memory research. With mice or other animals, memory can be monitored only through their behaviors. In order to examine the function of specific brain areas and cell populations amongst the incredible complexity of the brain, we employ highly specific genetic and transgenic manipulation techniques, often combined with optogenetic technologies. We subject these genetically engineered mouse strains along with control mice to a variety of analytical methods in order to detect the effect of a specific genetic manipulation. These methods include behavioral paradigms, in vivo electrophysiology, ex vivo patch clamp recordings, in vivo and in vitro optical calcium imaging, and molecular and cellular biology. Often, the discrepancy in results between the genetically modified and control mice reveals a particular deficiency or augmentation of the genetically modified mouse’s brain. This difference, referred to as a phenotype, when observed at various levels of organizational complexities, and associated specifically with the known genetic manipulation of the mutant mouse can be very informative in our understanding of brain mechanisms subserving behavior and cognition, and in disease states it can identify viable research targets for future therapies and cures.

Main Research Field

Biology

Keywords

  • Brain science
  • Neural circuits
  • Learning and memory

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, 484 381-385 (2012).
  2. Ramirez, S., Liu, X., Lin, P.A., Suh, J., Pignatelli, M., Redondo, R., Ryan, T.J., Tonegawa, S.:
    "Creating a False Memory in the Hippocampus"
    Science, 341 387-391 (2013).
  3. Redondo R., Kim J., Arons A., Ramirez S., Liu X., Tonegawa S.:
    "Bidirectional switch of the valence associated with a hippocampal contextual memory engram"
    Nature, 513 426-430 (2014).
  4. Ryan, T.J., Roy, D.S., Pignatelli, M., Arons, A., Tonegawa, S.:
    "Engram cells retain memory under retrograde amnesia"
    Science, 348: 941-1052 (2015).
  5. Ramirez, S., Liu, X., MacDonald C.J., Moffa, A., Zhou, J., Redondo, R.L.., Tonegawa, S.:
    "Activating positive memory engrams suppresses depression-like behaviour"
    Nature, 522: 335-339 (2015).
  6. Roy, D.S., Arons, A., Mitchell, T.I., Pignatelli, M., Ryan, T.J., Tonegawa, S.:
    "Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease"
    Nature. 531: 508-512 (2016).
  7. Okuyama, T., Kitamura, T., Roy, D.S., Itohara, S., Tonegaewa, S.:
    "Ventral CA1 neurons store social memory"
    Science. 353: 1536-1541 (2016).
  8. Kim, J., Pignatelli, M., Xu, S., Itohara, S., Tonegawa, S.:
    "Antagonistic negative and positive neurons of the basolateral amygdala"
    Nature Neuroscience, 19: 1636-1646 (2016).
  9. Kitamura, T.*, Ogawa, S.K.*, Roy, D.S.*, Okuyama, T., Morrissey, M., Smith, L.S., Redondo, R.L., Tonegawa, S.:
    "Engrams and circuits crucial for systems consolidation of a memory"
    Science, 356: 73-78 (2017).

Lab Members

Principal Investigator

Susumu Tonegawa
Laboratory Head

Core Members

Dennis King
Lab Manager/Research Specialist
Arek Hamalian
Financial Assistant II
Shu Ying Huang
Research Specialist
Chanel Lovett
Research Specialist
Mike Ragion
Research Specialist
Carrie Ragion
Research Specialist
Chris MacDonald
Research Scientist
Andrea BARI
Research Scientist
Michele Pignatelli di Spinazzola
Postdoctoral Associate
Takashi KAWAI
Postdoctoral Associate
Mark MORRISSEY
Postdoctoral Associate
Shruti MURALIDHAR
Postdoctoral Associate
Teruhiro Okuyama
Postdoctoral Fellow
Daigo Takeuchi
Postdoctoral Fellow
Frank Bushard
Technical Associate
Jayson Derwin
Technical Associate
Lily Smith
Technical Assistant
Carl Twiss
Technical Assistant
Wenjiang Yu
Technical Assistant
Jared Martin
Technical Assistant
Liam BRENNER
Spons. Res. Staff
Xiaoning Zhou
Spons. Res. Tech. Staff
Josh Kim
Graduate Student
Kaytee FLICK
Graduate Student
Rosary LIM
Graduate Student
Chen SUN
Graduate Student
Xiangyu ZHANG
Graduate Student

Contact information

77 Massachusetts Ave.
46-5285
Cambridge, MA 02139. USA

Email: tonegawa [at] mit.edu

Related links

Recent research results