Using optogenetics, a technique for genetically modifying cells, neurons in this case, in living animals so that their function can be turned on and off with light, the researchers controlled specific neurons that had been active during positive or negative experiences. The team was able to then evaluate how those particular neurons affect behavioral outcomes.

Those mice had been optogenetically modified so that the cells becoming light sensitive were only those that were most active during the positive or negative experience provided. For instance, the team was able to turn on only the positive-experience-associated cells to observe behavior in the mice.

By pairing the techniques in the same experiment, the team was able to determine not only that the molecular signature of the positive cells was different from those of the negative cells, but also that the positive and negative cells were wired to distant places in the brain in fundamentally differing ways.

"These cells are built differently," said Deisseroth. "They didn't start the same and then change their nature with recent experience. They appear wired specifically to communicate positive or negative experience."

Given the strong linkage between the prefrontal cortex and various psychiatric illness, he said the study opens the possibility of identifying and targeting different cell types with diverse therapeutic approaches, including drugs or external stimulation techniques.