One day while eating lunch, Gus heard the sound of a water glass shattering on the floor behind him and, turning, he saw his mother fall, too, and so she remained, bleeding and in pain. Two weeks later, hearing a water glass shatter in his schoolroom, John cringed in fear — apparently his brain had linked these two memories, so hearing the smashing sound once again, he felt the fear of seeing his mother hurt once again. This coupling phenomenon, according to a team of MIT neuroscientists, originates in two neural circuits in the brain, which work together to form time-linked memories.

“It's important for us to be able to associate things that happen with some temporal gap,” said Susumu Tonegawa, professor of biology and neuroscience at MIT. “For animals it is very useful to know what events they should associate and what not to associate.” In fact, Tonegawa believes this critical ability helps the brain maintain its balance between becoming too easily paralyzed with fear and becoming too careless, a necessary poise that helps us decide when to take action. His new research, conducted with a team, appears today in Science.

Episodic Memory

Episodic memory involves the recollection of events and it always contains three elements — what, where, and when. Unlike working memory, for instance, typing in an email address seen on TV, it is a type of long-term memory. Episodic memories are created in a brain structure called the hippocampus, which communicates with the many-layered entorhinal cortex in order to coordinate the three elements of what, where, and when. The entorhinal cortex, which sits just outside the hippocampus in the cerebral cortex, receives sensory information, including sights and sounds, from sensory processing areas of the brain and sends that information on to the hippocampus. Then, the hippocampus connects the dots of what, where, and when and forms a memory.

Previous research has revealed a great deal about the “where” of memory, the way the brain links the place component with the "what" or object component. Certain neurons in the hippocampus, known as place cells, are specialized to fire when we are in a specific location, and also when we are remembering that location. However, when it comes to associating objects with time — the "when" of memory — "our understanding has fallen behind,” Tonegawa stated in a press release. “Something is known, but relatively little compared to the object-place mechanism.”

Hippocampus and Entorhinal Cortex

To begin a new study of memory, the researchers built on knowledge gained from a previous investigation. The brain circuit which connects layer three of the entorhinal cortex to the CA1 region of the hippocampus was necessary for mice to link memories of two events — a tone and a mild electric shock — that occur up to 20 seconds apart. When that circuit, known as the monosynaptic circuit, was disrupted, however, the animals never learned to fear the tone.

For their new research, the researchers used optogenetics, a technology that allows specific populations of neurons to be turned on or off with light, to investigate the interplay of the monosynaptic circuit and another unknown circuit, which possesses the ability to suppress the monosynaptic circuit. In normal mice, the maximum time gap between events that can be linked is about 20 seconds, but through experimentation, the researchers discovered they could lengthen that period by either boosting activity of layer three cells or suppressing what they dubbed "island cells," which form circular clusters within layer two. Conversely, they could shorten the window of opportunity by inhibiting layer three cells or stimulating input from layer two island cells. Both of these actions always resulted 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. They continue their research at MIT's Picower Institute for Learning and Memory, which operates as an independent research entity within MIT's School of Science. The institute’s brain scientists are focused on unraveling the mechanisms that drive the human capacity to remember and to learn, as well as related functions like perception, attention, and consciousness.

 

 

Source:  Tonegawa S, Kitamura T, Pignatelli M. Island Cells Control Temporal Association Memory. Science. 2014.