Positive memories of an environment associated with cocaine can be rewritten, according to a study published online this week in Nature Neuroscience. Although previous studies have shown that memories can be artificially manipulated, this study demonstrates that such manipulation can be used to reverse maladaptive behavior, such as drug-seeking, in mice.
Neurons in the hippocampus called place cells are active when an animal is in a particular location in its environment. Recalling associations between a drug and a particular environment is thought to drive an animal to revisit a drug-paired location. However, because each place cell can contribute to multiple representations, it is unknown whether these can be selectively edited as a way of undoing the association between a particular place and an undesirable behavior.
Stephanie Trouche, David Dupret and colleagues trained mice to associate a particular environment with cocaine, leading the mice to prefer to spend more time in that environment than a similar environment paired with saline when given the choice. The authors then used a genetic technique to label place cells that were active in the cocaine-paired environment, which also caused the cells to express light-sensitive proteins. When they used light to silence the activity of these tagged neurons while the animals explored the cocaine-paired and saline-paired environments, the mice lost their preference for the former, suggesting that the memory had been recoded so that the environment was no longer associated with cocaine.