Lost And Found: Can We Restore Forgotten Memories?

Credit: Paul Yoakum

Memories are priceless, and the plight of dementia patients highlights how important they are to forming what makes us, well us. Now a new study has provided hope we may one day be able to restore lost memories. 

Clearing the mist

A paper from researchers at MIT has demonstrated the reactivation of memories in amnesia patients with optogenetics – in which cell activity is controlled by bursts of light. 

Could some memory loss be reversible?

There has been debate for some time about whether certain kinds of amnesia caused by damage, dementia or even stress are irreversible, or whether the memory is still there but access is somehow blocked. The theory claiming this amnesia is due to damage which prevents the cells from storing memory is called the Storage Theory. The alternative is that the memory remains stored, but is simply inaccessible; like an intact treasure chest whose location has been forgotten.

“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.”

Rebuilding the tracks

A mouse being tested with an optogenetics system

We now know that in order for a memory to be encoded, a population of neurons called memory engram cells are activated in the hippocampus. Input like smell, sound or emotion can then trigger these cells once more; opening up the memory. This new research at MIT has revealed that these engram cells undergo a long-term chemical change called ‘long-term potentiation’ (LTP). This strengthens synaptic signalling, and ensures frequently used memories form stronger connections. When the scientists activated a particular group of engram cells in the hippocampus using optogenetics, they were able to express a memory. 

“We were able to demonstrate for the first time that these specific cells — a small group of cells in the hippocampus — had undergone this augmentation of synaptic strength”

What happens if you take this consolidation away?

When the team used a compound called anisomycin to block protein synthesis while a memory was being formed, they were able to prevent these synapse connections from being strengthened. When they then attempted to activate the new memory with a trigger, it didn’t appear to be there. However When they then used optogenetics to activate the engram cells, despite the synaptic block they were able to initiate memory recall. 

“Without protein synthesis those cell synapses are not strengthened, and the memory is lost. If you test memory recall with natural recall triggers in an anisomycin-treated animal, it will be amnesiac, you cannot induce memory recall. But if you go directly to the putative engram-bearing cells and activate them with light, you can restore the memory, despite the fact that there has been no LTP” 

A groundbreaking development?

This work is potentially really important, because it shows multiple cells can be involved in memory recall, and that memories lost due to synaptic damage may still be lingering around. If that’s true, and the brain has lost a way to recall them naturally, it could pave the way for treatments like optogenetics which circumvent this block to reactivate the memories themselves. 

“The strengthening of engram synapses is crucial for the brain’s ability to access or retrieve those specific memories, while the connectivity pathways between engram cells allows the encoding and storage of the memory information itself”

Read more at MIT News