Study's mice swap memories' moods

Friday, August 29, 2014

For every memory, there's more than just a place, time and event. There's also an emotional context. But what if the feelings of fear associated with a traumatic event could be exchanged for happy ones?

Researchers at the Massachusetts Institute of Technology said they have done just that in mice, revealing the brain circuitry that makes good memories good and bad memories bad -- and how to manipulate it.

"Recording a memory is not like playing a tape recorder; it's a creative process," Susumo Tonegawa, director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT and senior author of the paper, said in a Nature news conference. The findings will be published in this week's Nature.

Psychotherapists already attempt to do this in patients with depression, Tonegawa explained, by trying to manipulate the emotional context of troubling memories. But whether or not there was a sound neurological basis for such techniques remained unclear until now.

The researchers used genetically engineered male mice who expressed a light-sensitive protein, allowing the scientists to activate different neurons by targeting them with a laser.

They exposed half of them to a positive stimuli (interaction with a female mouse) and half to a negative one (small electric shocks). This activated both the neurons that form the structure of a memory, which are found in the hippocampus, and the neurons that determine the emotional value of a memory, in the amygdala.

Then the mice were placed in a box with two sides that the mice could move freely between. When the mice moved to one particular end of the box, a light would shine down on them -- activating the neurons that had been active during their conditioning.

For the mice who had been shocked, the "target" end of the box meant an activation of the fearful memory. For the mice who'd spent time with a female, the same target end meant an activation of the pleasurable memory. The shocked mice avoided the target, while the others spent more time there than the side without a laser light.

This simply showed the researchers that they were activating the right regions of the brain to remind the mice of their emotional conditioning. The next step was to swap them around.

"The assumption here is that memories are formed between neurons that are active at the same time," Roger Redondo, a co-author of the study, said in the news conference. "So if this is right, we should be forcing the neurons associated with fear to begin with to link up with the new neurons expressing the pleasure of spending time with a female."

Male mice that had first received shocks had the same memory cells activated while they spent time with a female mice, and vice versa. Now, the very same experiment in the box had the opposite result: The mice who'd originally been remembering something pleasant when the light shone down on them now seemed to be experiencing fear and avoided the target area.

It's not clear if or how this could be translated to humans.

"There may be a lengthy process before this tech can be translated into human application," Redondo said, "but the circuits seem to be very similar between humans and mice when it comes to these memory associations and emotional memories."

And eventually, he said, an understanding of this circuitry could lead to new treatments for things like depression and post-traumatic stress disorder.

A Section on 08/29/2014