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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Scientists Trace Memories of Things That Never Happened

The vagaries of human memory are notorious. A friend insists you were at your 15th class reunion when you know it was your 10th. You distinctly remember that another friend was at your wedding, until she reminds you that you didn’t invite her. Or, more seriously, an eyewitness misidentifies the perpetrator of a terrible crime.

Not only are false, or mistaken, memories common in normal life, but researchers have found it relatively easy to generate false memories of words and images in human subjects. But exactly what goes on in the brain when mistaken memories are formed has remained mysterious.

Now scientists at the Riken-MIT Center for Neural Circuit Genetics at the Massachusetts Institute of Technology say they have created a false memory in a mouse, providing detailed clues to how such memories may form in human brains.


Podcast: Melding Two Memories Into One

From Science Friday: Reporting in Science, researchers write of linking a mouse's innocuous memory of a room with a more fearful memory of getting an electric shock—causing the mouse to freeze in fear upon seeing the safe room. Study author Steve Ramirez of M.I.T. and memory researcher Mark Mayford of The Scripps Research Institute discuss the implications for modifying human memories.

 



Podcast: Memory Test

Nature’s neuroscience podcast reporter Kerri Smith interviews Susumu Tonegawa via telephone regarding the research paper, “Optogenetic stimulation of a hippocampal engram activates fear memory recall,” by Xu Liu et al., which appeared in the April 19 issue of Nature. (The interview begins at 0:42.)



Light brings back bad memories

MIT researchers identify, label and manipulate the neuronal network encoding a memory

Memory is one of the enduring mysteries of neuroscience. How does the brain form a memory, store it, and then retrieve it later on? After a century of research, some answers began to emerge. It is now widely believed that memory formation involves the strengthening of connections between a network of nerve cells, and that memory recall occurs when that network is reactivated. There was, however, no direct evidence for this.

Now, researchers at MIT show that the cellular networks that encode memories can not only be identified, but also manipulated. In a spectacular study published online last week in the journal Nature, they report that they have labelled the network of neurons encoding a specific memory, and then reactivated the same network by artificial means to induce memory recall.


Podcast: the ‘preplay’ button

Nature’s neuroscience podcast reporter Kerri Smith interviews via telephone George Dragoi regarding the research paper, “Preplay of future place cell sequences by hippocampal cellular assemblies,” by George Dragoi and Susumu Tonegawa, which appeared in the Jan. 20, 2011 issue of Nature. (The interview begins at 12:11.)



A Nobel laureate’s stealthy biotech, its Japanese pharma backer, and the Englishman in charge

Outside of certain circles at MIT, you’d be hard pressed to find someone who is familiar with the biotech startup Galenea. The Cambridge, MA-based firm has been researching drugs for schizophrenia and other neurological disorders for more than five years, yet it has done so with a unique funding strategy that has kept its significant operation under the radar.

Galenea, founded in 2003 by MIT professor and Nobel laureate Susumu Tonegawa and others, has received the majority of its funding from the Japanese drug maker Otsuka Pharmaceutical, Mark Benjamin, the firm’s CEO, said. The startup has never raised a round of venture capital. And the company’s founders, employees, and Otsuka own the company.

Otsuka Pharmaceutical, a unit of Otsuka Holdings, began collaborating with Galenea in January 2005 and will have pumped $90 million into the startup’s research by the end of 2011. A focus of the collaboration has been on a defective protein, studied in Tonegawa’s lab at MIT and at Rockefeller University, which is believed to play a role in schizophrenia and other neurological dysfunctions. The aim is to find drugs that can modify the activity of the protein enough to treat a variety of mental disorders.



Potential to harness a newly uncovered mechanism of learning

By examining how we learn and store memories, Australian and American scientists have uncovered a new mechanism of learning that might prove useful in helping people who have lost their capacity to remember as a result of brain injury or disease.

The researchers have shown that the way the brain first captures and encodes a situation or event is quite different from the way it handles subsequent learning of similar events. It is this second stagelearning that holds promise if the process can be mimicked therapeutically.

Memories are formed in the part of the brain known as the ‘hippocampus’, a structure the shape of ram’s horns that passes through the right and left hemispheres. The hippocampus is very susceptible to damage through stroke or lack of oxygen, and is critically involved in Alzheimer’s disease.



Faculty profile: Susumu Tonegawa

Click here to view the article (p. 5) published in the fall 2009 newsletter by the Department of Brain and Cognitive Sciences (BCS) at MIT.

Susumu Tonegawa’s father and uncle were engineers and scientists, which was probably the initial influence in his deciding to pursue a career in science. By his senior year in college, fueled by the cornerstone papers by François Jacob and Jacques Monod of the Pasteur Institute, his interests were turning toward the nascent field of molecular biology. Molecular biology was just emerging as a discipline, and the lab of Professor Itaru Watanabe at the Institute for Virus Research at Kyoto University was one of Japan’s earliest pioneers in the field. However, Professor Watanabe encouraged Susumu to apply to UCSD, which was just being established. Professor Watanabe spoke with David Bonner, the head of the new Department of Biology there, and arranged for Susumu to attend the graduate school. At that point, Susumu knew nothing about the brain or prokaryotic molecular biology, but began by studying the field in the laboratory of Professor Masaki Hayashi. He then moved to the Salk Institute for 2 years, to the lab of Renato Dulbecco, who was to have a profound influence on his life. Professor Dulbecco was an expert in tumor virology, and Susumu wanted to study morecomplex systems with a focus on eukaryotic molecular biology.



Tonegawa rethinks Japan’s premier brain research center

Click here to view the full text of the interview published in Science on Oct. 16, 2009.

WAKO, JAPAN—Susumu Tonegawa, 70, has never shied away from challenges. He left Japan to earn a Ph.D. in molecular biology from the University of California, San Diego. After a postdoc at the Salk Institute for Biological Studies, also in San Diego, he joined the Basel Institute for Immunology in Switzerland, where he solved the riddle of how mammals produce billions of different antibodies needed to fend off infections—work that earned him the Nobel Prize in physiology or medicine in 1987.

Tonegawa was then at the Massachusetts Institute of Technology (MIT) in Cambridge, where he shifted his focus to neuroscience and in 1994 became the founding director of what is now called the Picower Institute for Learning and Memory at MIT. After a 2006 flap over the aborted hiring of a young female scientist at another MIT institute, Tonegawa gave up the directorship to concentrate on research. But this April, he became director of the RIKEN Brain Science Institute (BSI) in Wako, near Tokyo, a part-time arrangement that allows him to maintain a lab at MIT.

BSI was established in 1997 and now has more than 50 principal investigators (PIs) and a $100 million annual budget. Considered Japan’s flagship neuroscience institute, BSI is “pretty good,” Tonegawa says, but it doesn’t match the reputation and productivity of top U.S. and European neuroscience centers. Tonegawa spoke with Science earlier this month about how he intends to raise BSI’s game while coping with what he views as an inevitable downsizing.