Researchers Use Light To Recover ‘Lost’ Memories

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Do you remember what you had for lunch last Monday? Neither do I, but there’s no need to worry. It’s common to forget things every now and then, but life can be much harder for those who have developed amnesia from either a traumatic brain injury, stress or a neurological condition such as Alzheimer’s. But what exactly happens to these ‘lost’ memories? Using mice with amnesia as a model, researchers may have uncovered more about the nature of memory. The study, published in Science, has been able to find and retrieve lost memories with light.

Researchers from Massachusetts Institute of Technology (MIT) wanted to settle the debate on whether amnesia leads to ‘lost’ memories from damage to specific brain cells, or whether sufferers are unable to recall memories because of a ‘blockage’ in its storage.

"Brain researchers have been divided for decades on whether amnesia is caused by an impairment in the storage of a memory, or in its recall," says lead researcher Susumu Tonegawa, from the RIKEN-MIT Center for Neural Circuit Genetics, in a statement.

"The majority of researchers have favored the storage theory, but we have shown in this paper that this majority theory is probably wrong. Amnesia is a problem of retrieval impairment,” he adds.

Tonegawa and his research team first gave mice amnesia. They did this by training the mice to associate a mild foot shock with chamber A. So whenever mice entered chamber A, they would exhibit a typical ‘freezing’ behavior in response to the shock. The neurons that were activated during the formation of this memory were genetically labeled by researchers. To get one group of mice to ‘forget’ this memory, and thus suffer from amnesia, researchers inserted a chemical known as anisomycin to prevent protein synthesis and decrease the synaptic strength important for memory encoding. When the amnestic mice entered chamber A, they didn’t freeze, whereas the control group did.

Researchers then investigated whether this lost memory could be retrieved using optogenetic technology—a technique that uses light to activate proteins added to neurons. Using a blue light-sensitive protein, researchers were able to activate the specific neurons associated with the memory of the mild foot shock. Both the amnestic and control mice who were placed in a new environment, chamber B, exhibited the freezing behavior when researchers activated the cells involved in the foot shock memory.

The findings of the study suggest that there are different processes in the brain that control how memories are stored and recalled. Researchers suggest that the key lies in a process known as memory consolidation, where groups of neurons undergo a durable chemical change. They saw a specific change called "long-term potentiation," where the strength of the synapses were increased as a result of learning and experience.

When anisomycin was administered to the mice, researchers were able to block protein synthesis from occurring within neurons, which prevented the synapses from strengthening. Researchers then attempted to retrieve the memory through an emotional trigger, but were unable to as “without protein synthesis those cell synapses are not strengthened, and the memory is lost," Tonegawa explains. When researchers reactivated the protein synthesis, they found that the memory had been retrieved and the mice exhibited the freezing behavior. Tonegawa suggests that memory cannot be recalled by “natural” triggers, but can be found if researchers directly activate the memories stored in neurons. 

"Our conclusion is that in retrograde amnesia, past memories may not be erased, but could simply be lost and inaccessible for recall. These findings provide striking insight into the fleeting nature of memories, and will stimulate future research on the biology of memory and its clinical restoration," says Tonegawa. 

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