Scientists Experiment With Reworking Memory in MiceTesting Rewires Circuits of Brain, Changes Bad Memories to GoodThe Wall Street Journal
By Gautam Naik Updated Aug. 27, 2014 1:22 p.m. ET
In experiments on mice, scientists rewired the circuits of the brain and changed the animals' bad memories into good ones.
The rewriting of the memory wasn't done with drugs but by using light to control the activity of brain cells. While science is a long way from achieving a similar feat in people, it adds to a body of research that is starting to uncover the physiological basis of memory.
"This could pave the way to rewire the circuits in the brain" to treat disorders such as post-traumatic stress syndrome, depression or other psychiatric illnesses, said Roger Redondo, neuroscientist at the Massachusetts Institute of Technology and lead author of the study, published Wednesday in the journal Nature.
A memory is created when a past experience becomes encoded in a network of neurons in the brain. The memory is recalled when the neurons fire in a particular sequence.
Some aspects of the memory can endure a long time, while others are more fickle. "The memory of a romantic first meal out with a partner may take on a different mood when the relationship falters," said Tomonori Takeuchi and Richard Morris at the University of Edinburgh, in an article accompanying the study. "In these cases, memory of the place remains accurate, but the positive associations with that place are lost."
White mouse. Published Credit: Photo Researchers/Getty Images White mouse. Published Credit: Photo Researchers/Getty Images Getty Images/Photo Researchers RDr. Redondo and his MIT colleagues set out to answer two questions: Which specific circuits in the brain store our good and bad memories? And can a good memory be changed to a bad one; and vice versa?
The researchers established that the "where" of a memory is encoded in cells found in a brain structure called the hippocampus, while the "emotion" linked to it —whether one feels good or bad about the place—is embedded in a brain area called the amygdala. The two parts of the brain are connected.
The MIT team wanted to see if it could change the association between the "where" of the memory and the "emotion" linked with it. To get there, they used a cutting-edge technique known as optogenetics, which uses light to control brain cells that have been genetically sensitized to it.
In the case of the mice, a fiber-optic cable was inserted via a tiny hole in the animal's skull, allowing a laser beam to be fired through the wire to activate individual neurons in the brain.
They began by giving one set of male mice fearful memories (via a small electric shock to the foot) and by providing other mice with pleasurable memories (by allowing them to interact with female mice). By firing the laser into the mouse brain, the scientists could identify the specific cells that were activated when each of the two memories were formed.
That was followed by a "place-preference" test. A laser was fired to the mouse brain when the animal entered a designated area, which activated the previously identified brain cells. When this was done, the fear-conditioned mice moved away from the target zone, while the pleasure-conditioned mice lingered in that area longer because they recalled the positive memory.
The next day, the fear-conditioned mice were placed in a different area. There, they were allowed to interact with female mice, while the fear-associated memory cells were artificially stimulated with the laser. The scientists hoped that the pleasurable exposure to the female mice would rewire the males' previously fear-conditioned circuits.
To test this, the male mice were returned to the original target zone. When the laser was again used to stimulate the neurons, they now lingered longer in the target zone. This indicated that their original fear-conditioned circuit had been changed to one associated with pleasure.
The researchers said they were able to do the opposite as well—change a pleasurable memory in mice into one associated with fear.
"We identified the circuit, and we've showed that we can manipulate such circuits artificially," said Dr. Redondo.
It isn't practical to fire lasers into human brains under a similar setup. But the Nature experiment could inspire other approaches that may prove medically useful. For example, now that the memory-forming circuit has been identified, it may be possible to influence it by other means, such as using a drug.
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