Study reveals how the brain links memories of sequential events

January 23, 2014 by Anne Trafton, Massachusetts Institute of Technology
This is an image of Island cells. Green shows axons of Island cells. Blue shows the nuclei. Red shows the marker of CA2 region. Credit: RIKEN

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 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."

The interaction of these two circuits allows the brain to maintain a balance between becoming too easily paralyzed with fear and being too careless, which could result in being caught off guard by a predator or other threat.

The paper's lead authors are Picower Institute postdocs Takashi Kitamura and Michele Pignatelli.

Linking memories

Memories of events, known as , always contain three elements—what, where, and when. Those memories are created in a brain structure called the hippocampus, which must coordinate each of these three elements.

To form episodic memories, the hippocampus also communicates with the region of the cerebral cortex just outside the hippocampus, known as the entorhinal cortex. The entorhinal cortex, which has several layers, receives sensory information, such as sights and sounds, from sensory processing areas of the brain and sends the information on to the hippocampus.

This is an image of cells making clusters in the entorhinal cortex layer II. Green shows Island cells. Red shows Ocean cells. Credit: RIKEN

Previous research has revealed a great deal about how the brain links the place and object components of . Certain neurons in the hippocampus, known as place cells, are specialized to fire when an animal is in a specific location, and also when the animal is remembering that location. However, when it comes to associating objects and time, "our understanding has fallen behind," Tonegawa says. "Something is known, but relatively little compared to the object-place mechanism."

The new Science paper builds on a 2011 study from Tonegawa's lab in which he identified a brain circuit necessary for mice to link memories of two events—a tone and a mild electric shock—that occur up to 20 seconds apart. This circuit connects layer 3 of the to the CA1 region of the . When that circuit, known as the monosynaptic circuit, was disrupted, the animals did not learn to fear the tone.

In the new paper, the researchers report the discovery of a previously unknown circuit that suppresses the monosynaptic circuit. This signal originates in a type of excitatory neurons discovered in Tonegawa's lab, dubbed "island cells" because they form circular clusters within layer 2. Those cells stimulate inhibitory neurons in CA1 that suppress the set of excitatory CA1 neurons that are activated by the monosynaptic circuit.

Deciphering circuits

The researchers used optogenetics, a technology that allows specific populations of neurons to be turned on or off with light, to demonstrate the interplay of these two circuits.

In normal mice, the maximum time gap between events that can be linked is about 20 seconds, but the researchers could lengthen that period by either boosting activity of layer 3 cells or suppressing layer 2 island cells. Conversely, they could shorten the window of opportunity by inhibiting layer 3 cells or stimulating input from layer 2 island cells, which both result in turning down CA1 activity.

The researchers hypothesize that prolonged CA1 activity keeps the memory of the tone alive long enough so that it is still present when the shock takes place, allowing the two memories to be linked. They are now investigating whether CA1 neurons remain active throughout the entire gap between events.

Explore further: Modifying activity of neuronal networks that encode spatial memories leads to formation of incorrect fear memory in mice

More information: "Island Cells Control Temporal Association Memory" Science, 2014.

Related Stories

Modifying activity of neuronal networks that encode spatial memories leads to formation of incorrect fear memory in mice

September 13, 2013
The formation and retrieval of memories allows all kinds of organisms, including humans, to learn and thrive in their environment. Yet our memories are not always accurate, and mistaken remembrances can have important consequences, ...

Neuroscientists show ability to plant false memories

July 25, 2013
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 pauses that refresh the memory

November 29, 2013
Sufferers of schizophrenia experience a broad gamut of symptoms, including hallucinations and delusions as well as disorientation and problems with learning and memory. This diversity of neurological deficits has made schizophrenia ...

Schizophrenia linked to abnormal brain waves

October 16, 2013
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 ...

Study identifies drug that could improve treatment of posttraumatic stress disorder

January 16, 2014
Nearly 8 million Americans suffer from posttraumatic stress disorder (PTSD), a condition marked by severe anxiety stemming from a traumatic event such as a battle or violent attack.

Brain circuits connected with memory discovered

November 7, 2011
(Medical Xpress) -- A new study published last week in Science reveals the discovery of a brain pathway that helps us link events that happen close together and play a role in memories.

Recommended for you

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

A 'touching sight': How babies' brains process touch builds foundations for learning

January 16, 2018
Touch is the first of the five senses to develop, yet scientists know far less about the baby's brain response to touch than to, say, the sight of mom's face, or the sound of her voice.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.