Neuroscientists identify brain circuit necessary for memory formation

New findings challenge standard model of memory consolidation.

When we visit a friend or go to the beach, our brain stores a short-term memory of the experience in a part of the brain called the hippocampus. Those memories are later “consolidated” — that is, transferred to another part of the brain for longer-term storage.

A new MIT study of the neural circuits that underlie this process reveals, for the first time, that memories are actually formed simultaneously in the hippocampus and the long-term storage location in the brain’s cortex. However, the long-term memories remain “silent” for about two weeks before reaching a mature state.

Neuroscientists identify brain circuit that drives pleasure-inducing behavior

Surprisingly, the neurons are located in a brain region thought to be linked with fear.

Scientists have long believed that the central amygdala, a structure located deep within the brain, is linked with fear and responses to unpleasant events.

However, a team of MIT neuroscientists has now discovered a circuit in the central amygdala that responds to rewarding events. In a study of mice, activating this circuit with certain stimuli made the animals seek those stimuli further. The researchers also found a circuit that controls responses to fearful events, but most of the neurons in the central amygdala are involved in the reward circuit, they report.

Neuroscientists identify two neuron populations that encode happy or fearful memories

A delicate balance between positive and negative emotion

Our emotional state is governed partly by a tiny brain structure known as the amygdala, which is responsible for processing positive emotions such as happiness, and negative ones such as fear and anxiety.

A new study from MIT finds that these emotions are controlled by two populations of neurons that are genetically programmed to encode memories of either fearful or pleasurable events. Furthermore, these sets of cells inhibit each other, suggesting that an imbalance between these populations may be responsible for disorders such as depression and post-traumatic stress disorder.

Scientists identify neurons devoted to social memory

Cells in the hippocampus store memories of acquaintances, a new study reports.

Mice have brain cells that are dedicated to storing memories of other mice, according to a new study from MIT neuroscientists. These cells, found in a region of the hippocampus known as the ventral CA1, store “social memories” that help shape the mice’s behavior toward each other.

The researchers also showed that they can suppress or stimulate these memories by using a technique known as optogenetics to manipulate the cells that carry these memory traces, or engrams.

“You can change the perception and the behavior of the test mouse by either inhibiting or activating the ventral CA1 cells,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory.

Tonegawa is the senior author of the study, which appears in the Sept. 29 online edition of Science. MIT postdoc Teruhiro Okuyama is the paper’s lead author.

“Lost” memories can be found

Neuroscientists retrieve missing memories in mice with early Alzheimer’s symptoms.

In the early stages of Alzheimer’s disease, patients are often unable to remember recent experiences. However, a new study from MIT suggests that those memories are still stored in the brain — they just can’t be easily accessed.

The MIT neuroscientists report in Nature that mice in the early stages of Alzheimer’s can form new memories just as well as normal mice but cannot recall them a few days later.

Furthermore, the researchers were able to artificially stimulate those memories using a technique known as optogenetics, suggesting that those memories can still be retrieved with a little help. Although optogenetics cannot currently be used in humans, the findings raise the possibility of developing future treatments that might reverse some of the memory loss seen in early-stage Alzheimer’s, the researchers say.

How the brain encodes time and place

Neuroscientists identify a brain circuit that is critical for forming episodic memories.

When you remember a particular experience, that memory has three critical elements — what, when, and where. MIT neuroscientists have now identified a brain circuit that processes the “when” and “where” components of memory.

This circuit, which connects the hippocampus and a region of the cortex known as entorhinal cortex, separates location and timing into two streams of information. The researchers also identified two populations of neurons in the entorhinal cortex that convey this information, dubbed “ocean cells” and “island cells.”

Previous models of memory had suggested that the hippocampus, a brain structure critical for memory formation, separates timing and context information. However, the new study shows that this information is split even before it reaches the hippocampus…

Recalling happier memories can reverse depression

Artificially reactivating positive memories could offer an alternative to traditional antidepressants.

MIT neuroscientists have shown that they can cure the symptoms of depression in mice by artificially reactivating happy memories that were formed before the onset of depression.

The findings, described in the June 18 issue of Nature, offer a possible explanation for the success of psychotherapies in which depression patients are encouraged to recall pleasant experiences. They also suggest new ways to treat depression by manipulating the brain cells where memories are stored. The researchers believe this kind of targeted approach could have fewer side effects than most existing antidepressant drugs, which bathe the entire brain…

Kerri Smith

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…

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-M.I.T. 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…

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.

Where goest thou, O thought?

The search for the memory trace, or ‘engram,’ began in the 1920s, with the work of a Canadian neurosurgeon named Wilder Penfield, who pioneered a technique for electrically stimulating the surface of the brain. Penfield’s aim was to identify and remove brain tumours, or abnormal tissue that caused severe epileptic seizures, while sparing surrounding tissue that controls essential functions like speech or movement…

Kerri Smith

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)

Kerri Smith

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 stage learning 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…

Tonegawa rethinks Japan’s premier brain research center

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…