SAN FRANCISCO, March 24 (Xinhua) -- Stanford University researchers have built on Russian physiologist Ivan Pavlov's job more than 100 years ago to observe how large groups of neurons in the brain both learn and unlearn a new association.
In the decades following the work by Pavlov and his famous salivating dogs, scientists have discovered how molecules and cells in the brain learn to associate two stimuli, like Pavlov's bell and the resulting food.
What they haven't been able to study is how whole groups of neurons work together to form that association.
"It's been over 100 years since Pavlov did his amazing work but we still haven't had a glimpse of how neural ensembles encode a long-term memory," said Mark Schnitzer, associate professor of biology and applied physics, who led the research and published their findings this week in Nature. "This was an opportunity to examine that."
Working with mice and focused on the amygdala, a part of the brain known to be involved in learning that is extremely similar across species, the researchers trained mice to associate a tone with a light foot shock.
At the beginning of the experiment, mice had no reaction to the tone, but would freeze in place in response to the light shock.
After pairing the tone and the light shock a few times, the tone alone was enough to cause the mice to freeze in place, meaning that once the mice learned the association, the pattern of neurons that activated in response to tone alone resembled the pattern that activated in response to the shock.
Using Pavlov's dogs as an analogy, this would mean that, as the dogs learned to associate the bell with the food, the neural network activation in their amygdalas would look similar whether they were presented with food or just heard the bell.
"You can think of this type of learning as a survival strategy," Benjamin Grewe, lead author of the paper and former postdoctoral scholar in the Schnitzer lab, was quoted as saying in a news release. "We need that as humans, animals need that. When we associate certain stimuli with their possible dangerous outcomes, it helps us to avoid dangerous situations in the first place."
During the training, using a miniature microscope to view about 200 neurons in the amygdala, the researchers could observe activity of individual cells as well as of the entire ensemble, finding that, as the mice learned to associate the tone with the shock, the set of cells that responded to the tone began to resemble those that responded to the shock itself.
"The two stimuli are both eliciting fear responses," said Schnitzer. "It's almost as if this part of the brain is blurring the lines between the two, in the sense that it's using the same cells to encode them."
As part of the experiments, the team undid the conditioning so that the mice stopped freezing in reaction to the tone. However, the researchers found, the neural response never completely returned to its original state.
Findings in this phase of experiment, which was not designed to represent any human diseases or disorders, could potentially have wide-ranging implications for studying emotional memory disorders, such as post-traumatic stress disorder (PTSD).