MIT neuroscientists build case for new theory of memory formation

Existence of “silent engrams” suggests that existing models of memory formation should be revised.

Learning and memory are generally thought to be composed of three major steps: encoding events into the brain network, storing the encoded information, and later retrieving it for recall.

Two years ago, MIT neuroscientists discovered that under certain types of retrograde amnesia, memories of a particular event could be stored in the brain even though they could not be retrieved through natural recall cues. This phenomenon suggests that existing models of memory formation need to be revised, as the researchers propose in a new paper in which they further detail how these “silent engrams” are formed and re-activated.

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…

Researchers find “lost” memories

Scientists use optogenetics to reactivate memories that could not otherwise be retrieved.

Memories that have been “lost” as a result of amnesia can be recalled by activating brain cells with light.

In a paper published today in the journal Science, researchers at MIT reveal that they were able to reactivate memories that could not otherwise be retrieved, using a technology known as optogenetics.

The finding answers a fiercely debated question in neuroscience as to the nature of amnesia, according to Susumu Tonegawa, the Picower Professor in MIT’s Department of Biology and director of the RIKEN-MIT Center at the Picower Institute for Learning and Memory, who directed the research by lead authors Tomas Ryan, Dheeraj Roy, and Michelle Pignatelli…

Neuroscientists Reverse Memories’ Emotional Associations

Most memories have some kind of emotion associated with them: Recalling the week you just spent at the beach probably makes you feel happy, while reflecting on being bullied provokes more negative feelings.

A new study from MIT neuroscientists reveals the brain circuit that controls how memories become linked with positive or negative emotions. Furthermore, the researchers found that they could reverse the emotional association of specific memories by manipulating brain cells with optogenetics — a technique that uses light to control neuron activity.

The findings, described in the Aug. 27 issue of Nature, demonstrated that a neuronal circuit connecting the hippocampus and the amygdala plays a critical role in associating emotion with memory. This circuit could offer a target for new drugs to help treat conditions such as post-traumatic stress disorder, the researchers say.

“In the future, one may be able to develop methods that help people to remember positive memories more strongly than negative ones,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory, and senior author of the paper.

How Mice Think

MIT research sheds light on retrieving correct memories and how animals “think” when they self-correct their on-going behaviors.

Mice running mazes sometimes go left when they should go right. MIT’s Picower Institute for Learning and Memory researchers report in the April 24 online version of Cell that a certain pattern of brain waves pinpointed the precise moment the rodents chose the correct path to the reward–as well as when they noticed their errors. They also discovered that these brain waves appear in a delayed manner when animals changed their mind and self-corrected to correctly perform the task.

In humans and animals, rhythmic electrical oscillations produced by millions of neurons firing in sync are thought to play a role in memory formation and retrieval. For the first time, Picower Institute neuroscientists linked a specific synchronized oscillation pattern with its correlating behavior.

The work may lead to new therapies for patients suffering from Alzheimer’s disease and other memory impairments. What’s more, the results indicated that the trained mice in the study recognized and reversed their “oops” moments, raising tantalizing questions about the extent to which animals can analyze and control their own cognitive processes…

In the brain, timing is everything

Study reveals how the brain links memories of events that occur one after the other.

Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow — suggesting that somehow, your brain had linked those two memories so that a fairly innocuous sound provokes dread.

MIT neuroscientists have now discovered how two neural circuits in the brain work together to control the formation of such time-linked memories. This is a critical ability that helps the brain to determine when it needs to take action to defend against a potential threat, says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the Jan. 23 issue of Science.

“It’s important for us to be able to associate things that happen with some temporal gap,” says Tonegawa, who is a member of MIT’s Picower Institute for Learning and Memory. “For animals it is very useful to know what events they should associate, and what not to associate.”…

Discovering hippocampal connections responsible for episodic memory

MIT neuroscientists map neural circuits involving the CA2 region of the hippocampus.

The hippocampus is the region of the brain that is responsible for episodic memory. For decades, neuroscientists have been mapping the hippocampus’s neural circuits to better understand how memories are stored, retrieved, and lost.

The trisynaptic circuit, discovered by the legendary anatomist Santiago Ramón y Cajal more than 100 years ago, has long been considered the anatomical substrate responsible for learning and memory. But the trisynaptic circuit involved only the entorhinal cortex and the dentate gyrus, CA1 region and CA3 region of the hippocampus; the tiny CA2 region of the hippocampus, located between CA1 and CA3, was not thought to play a critical role.

When a 2005 study using molecular cell markers revealed that the CA2 region might be wider than previously thought, neuroscientists began to wonder whether CA2 had a role in memory. To address this, scientists needed to know more about the CA2 region’s boundaries and its neural connections to CA1 and CA3. But traditional methodologies like dye injections and electrophysiological stimulation of axon bundles haven’t been up to the task…

Schizophrenia linked to abnormal brain waves

Neuroscientists discover neurological hyperactivity that produces disordered thinking.

Schizophrenia patients usually suffer from a breakdown of organized thought, often accompanied by delusions or hallucinations. For the first time, MIT neuroscientists have observed the neural activity that appears to produce this disordered thinking.

The researchers found that mice lacking the brain protein calcineurin have hyperactive brain-wave oscillations in the hippocampus while resting, and are unable to mentally replay a route they have just run, as normal mice do.

Mutations in the gene for calcineurin have previously been found in some schizophrenia patients. Ten years ago, MIT researchers led by Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, created mice lacking the gene for calcineurin in the forebrain; these mice displayed several behavioral symptoms of schizophrenia, including impaired short-term memory, attention deficits, and abnormal social behavior…

Neuroscientists plant false memories in the brain

MIT study also pinpoints where the brain stores memory traces, both false and authentic.

The phenomenon of false memory has been well-documented: In many court cases, defendants have been found guilty based on testimony from witnesses and victims who were sure of their recollections, but DNA evidence later overturned the conviction.

In a step toward understanding how these faulty memories arise, MIT neuroscientists have shown that they can plant false memories in the brains of mice. They also found that many of the neurological traces of these memories are identical in nature to those of authentic memories.

“Whether it’s a false or genuine memory, the brain’s neural mechanism underlying the recall of the memory is the same,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of “Creating a false memory in the hippocampus” paper published in the July 25 edition of Science…

Researchers reverse Fragile X Syndrome symptoms in adult mice

Picower Institute neuroscientists use single dose of experimental drug; could prove promising for treatment of autism symptoms.

Neuroscientists at MIT’s Picower Institute for Learning and Memory report in the March 18 Proceedings of the National Academy of Sciences (PNAS) that they have reversed autism symptoms in adult mice with a single dose of an experimental drug.

The work from the laboratory of Nobel laureate Susumu Tonegawa, the Picower Professor in the Department of Biology and a principal investigator at the Picower Institute, points to potential targets for drugs that may one day improve autism symptoms such as hyperactivity, repetitive behaviors and seizures in humans by modifying molecular mechanisms underlying the disease.

“These findings suggest a possible novel therapeutic target for the treatment of Fragile X Syndrome (FXS) — the most common inherited form of autism and intellectual disability,” said Eric Klann, a professor of neural science at New York University…