Not-So-Total Recall: Selectively Erasing Unwanted Memories

Scientists at The Scripps Research Institute (TSRI) are exploring a technique that may permit the selective disruption of harmful or unpleasant memories. The scientists report that they have been able to erase drug-associated memories in mice and rats without affecting other, more benign memories. Aware that memories associated with drugs of abuse may lead to cravings in recovering addicts, the scientists speculate that eliminating such memories may prevent relapses among recovering addicts. Other potential applications include sparing PTSD sufferers the pain of past memories.

"Our memories make us who we are, but some of these memories can make life very difficult," said Courtney Miller, Ph.D., a TSRI assistant professor who led the research. "Not unlike in the movie Eternal Sunshine of the Spotless Mind, we're looking for strategies to selectively eliminate evidence of past experiences related to drug abuse or a traumatic event. Our study shows we can do just that in mice-;wipe out deeply engrained drug-related memories without harming other memories."

In the tests, animals were trained to associate the rewarding effects of methamphetamine with a rich context of visual, tactile, and scent cues. When injected with an inhibitor of actin polymerization many days later in their home environment, the animals later showed a complete lack of interest when they encountered drug-associated cues. At the same time, the response to other memories, such as food rewards, was unaffected.

Actin polymerization was inhibited by blocking a molecular motor called mysosin II in the brains of mice and rats during the maintenance phase of memory formation. By blocking actin polymerization, the scientists believe that they were able to prevent actin-mediated structural changes crucial to memory formation. In particular, inhibiting actin polymerization prevented structural changes in dendritic spines, small, bulb-like structures that allow neurons to receive electrochemical signals from other neurons.

In the study, the scientists note that although there is a growing consensus that memory is supported by structural and functional plasticity driven by actin polymerization in postsynaptic dendritic spines at excitatory synapses, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown.

It remains unclear why powerful methamphetamine-related memories are also so fragile, but this study's scientists think that their findings could be related to the role of dopamine, a neurotransmitter involved in reward and pleasure centers in the brain and known to modify dendritic spines. Previous studies had shown dopamine is released during both learning and drug withdrawal. Dr. Miller adds, "We are focused on understanding what makes these memories different. The hope is that our strategies may be applicable to other harmful memories, such as those that perpetuate smoking or PTSD."

In the study, the scientists conclude that their results point to a "potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory." They add that "the results further suggest that memory maintenance depends upon the preservation of polymerized actin."

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