Memory re-writing experiments in mice uncover the brain circuits involved in altering memories. The researchers found that they could reverse the emotional association of specific memories by manipulating brain cells with optogenetics - a technique that uses light to control neuron activity. The findings, reported in Nature this week, provide detailed understanding of how emotional memories can be manipulated and suggest emotional memory associations can be changed at the circuit level.
Memories typically carry either positive or negative emotional associations that can change over time while other details of the memory, such as a physical location, remain accurate. The processes that enable the emotion associated with memories to switch are largely unknown, although it is believed that distinct regions of the brain store different aspects of a memory.
Susumu Tonegawa and colleagues studied how cells in part of the amygdala (thought to encode positive or negative feelings) and the dentate gyrus of the hippocampus (thought to encode contextual information) of mice are activated during memory formation. Male mice were conditioned with either fearful memories (by being given a small electric shock) or rewarding memories (interacting with a female mouse), causing the animals to either avoid or prefer a certain location when the memory was reactivated optogenetically. Then, to switch the positive or negative memory associated with a group of neurons, the mice were subjected to conditioning of the opposite emotional experience while the memory neurons were artificially activated by light.
The researchers found that when the neural circuits in the dentate gyrus were activated during attempts to reverse memories, it led to a change in connectivity between the memory traces (or engrams) in the dentate gyrus and the amygdala. Thus, this work indicates that emotional memory traces in the dentate gyrus can be re-written to form new emotional memory associations within a given context or location.