Neuroscientists reactivate memories lost as a result of amnesia through optogenetics

For many years, scientists have wondered if retrograde amnesia is associated with damage to specific brain cells.  Retrograde amnesia is a condition where memory would be blocked to prevent its recall.  According to Prof Susumu Tonegawa from Massachusetts Institute of Technology, “The majority of scientists have favored the storage theory, but we have shown in the study that this majority theory is probably wrong. Amnesia is a problem of retrieval impairment.”

Researchers used to believe that somewhere in the network within the brain, a population of neurons activated during memory causes physical or chemical changes then when a sight or smell serves as a trigger, the memory may be recalled.

Through Tonegawa’s study, they did, in fact, confirm that a population of neurons exists in the hippocampus of the brain.  Yet, these groups of neurons do undergo long chemical changes through memory consolidation.

Through the study, the researchers were able to show that in mice, traces of old memories do stay in the amnesic brain, and you can reactivate the “lost” memories in the cellular pathways.

 “traces of old memories do stay in the amnesic brain, and you can reactivate the “lost” memories in the cellular pathways”

To make the mice in the study amnesic, the researchers trained the mice to associate a mild foot shock with an environment, chamber A.  This creates a “freezing” behavior.  Tonegawa explained, “Eventually, trained mice would freeze in chamber A even without the shock. Neurons activated during memory formation were genetically labeled to allow their visualization and reactivation.”

After that, the mice are given anisomycin to inhibit protein synthesis and prevent strengthening at the synapses to induce retrograde amnesia.  Reflecting on this, Tonegawa said, “As expected, amnesic mice returned to chamber A did not freeze, indicating that they could not recall the memory for the specific association of the chamber and the mild foot shock.”

The scientists then tried to see if the mice no longer remembered the foot-shock training in chamber A or if it was present but not retrievable.  Using optogenetics, they activated certain neurons with a blue light-sensitive protein called channelrhodopsin in a new environment.  The amnesic mice did, in fact, freeze in this environment just like the control mice who only received saline.  This demonstrated that they remembered the memory even though they couldn’t recall it in chamber A.

The scientists attempted to explain this behavior by saying that different processes control memory encoding and recall which is associated with the recalling of a “lost” memory during light stimulation.

Prof. Tonegawa concluded, “Our conclusion is that in retrograde amnesia, past memories may not be erased, but could simply be lost and inaccessible for recall.”

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