image: Behavi oral expression of fear memory: In n aïve (unlearned) state, mice have not gained a context - specific engram. In the learned memory state, mice have acquired a synapticaly potentiated fear engram, which causes them to express freezing be havior in the fearful context. In the amnesia state, protein synthesis inhibition has resulted in mice that have an interrupted and synaptically depotentiated fear engram, which does not cause freezing behavior in the fearful context, but can resul t in freezing behavior if directly activated. view more
Credit: [Credit: Dheeraj Roy ]
This news release is available in Japanese.
Memories that have been destabilized and forgotten by mice can nevertheless be retrieved by activating memory engrams, or specific patterns of neurons that fire when memories are encoded, with light, researchers say. These findings provide fresh insight into memory consolidation, or the process by which new, unstable memories transform into stable, long-term memories. Until now, researchers have wondered whether memory consolidation was dependent upon the stabilization of these memory engrams. But Tomás Ryan and colleagues show that this is not the case in mice with retrograde amnesia. The researchers first studied hippocampal neurons of healthy mice during a fear-conditioning exercise, observing that engram cells had stronger synapses and denser dendritic spines than non-engram cells. They tagged those engram cells with a light-sensitive protein and then injected some of their mice with a protein synthesis inhibitor known as anisomycin (ANI) 24 hours later. The ANI prevented the increase of the synaptic strength and dendritic spine density of the rodents' engram cells, causing the injected mice to forget the fear-conditioning they had experienced the day before. Surprisingly, Ryan and his team were able to use light to overcome this retrograde amnesia, restoring the rodents' fearful memories by activating the engram cells that had been tagged with the light-sensitive protein during fear-conditioning. Taken together, these findings suggest that engram cells are needed for encoding memories, and that the strengthened synapses in such cells play a critical role in the memory retrieval process. The researchers' optogenetic approach for studying memory consolidation might also be applicable to other experimental and clinical cases of amnesia, such as Alzheimer's disease, they say.
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Article #12: "Engram cells retain memory under retrograde amnesia," by T.J. Ryan; D.S. Roy; M. Pignatelli; A. Arons; S. Tonegawa at Massachusetts Institute of Technology in Cambridge, MA; T.J. Ryan; D.S. Roy; M. Pignatelli; A. Arons; S. Tonegawa at RIKEN in Cambridge, MA; T.J. Ryan; A. Arons; S. Tonegawa at Howard Hughes Medical Institute in Cambridge, MA.
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Science