Engineered Viruses Boost Memory Recall in Mice

Memories fade with time, often to the annoyance of those who can’t recall important details. But scientists have now found a way to boost the recall of memories even after they’ve started to fade. Unfortunately, the method involves injecting an engineered virus directly into the brain, so those of us who are bad with names may want to wait a bit for the technique to be refined.

The work was done in rats, and the memories in question are associations between a specific taste — saccharine, for example — and an unpleasant stimulus, caused by injection of a nausea-inducing drug (the approach is called “conditioned taste aversion”). Unless the unpleasant association is reinforced, the memories will slowly fade with time, although the aversion doesn’t disappear entirely during the two-week period that the authors were looking at.

Two years ago, the same authors found that it was possible to radically accelerate this fading. By injecting a chemical that blocked a specific brain enzyme (protein kinase M ζ), the authors caused the rats to act as if they had never experienced the nausea, even if the memory manipulation took place 25 days after the conditioning. Most chemicals that interfere with memories tend to prevent them from being consolidated for long-term storage, but this chemical seemed to work even after the memory was firmly in place.

That’s potentially helpful, since some people have formed negative associations with harmless or even helpful items. Still, for most of us, it would be nice to think that fading memories could be resuscitated. Apparently, they can. The researchers have now done what’s effectively the converse experiment, and increased the activity of protein kinase M ζ. They did this by engineering a virus to express the gene for the kinase, and then infected specific areas of the brain involved in memory. All the infected cells had additional copies of the gene, and thus made more of its product.

The virus had exactly the effect that the authors would presumably have predicted. The virus was injected a week after the rats were given the aversion conditioning, when the memory would already be starting to fade, and the memory tests were done a week after that, yet rats showed a significantly improved retention of their memories. As the authors point out, the engineered virus boosted a memory that was formed before it was even present.

The memory molecule, PKMzeta, overexpressed in rat neurons. Red (left) shows PKMzeta while green (middle) is a fluorescent protein that shows nerve cells have been infected by viruses engineered to boost the memory molecule. Yellow (right) shows both the memory molecule and green fluorescent protein only overexpress at certain locations in the neuron. Weizmann Institute of Science/Science

Actually, you can make that memories, plural. The authors trained rats to avoid both saccharine and salty liquids over the course of three days, and then injected the virus a week after the last training. The memories of both of these trainings were enhanced by the presence of the viral protein kinase M ζ gene.

The authors can’t tell exactly what protein kinase M ζ is doing to increase the recall of memories, and suggest it could be either enhancing the association between taste and the unpleasant experience, or simply enhancing recall in general. Although they don’t mention it, their findings may also be limited to specific classes of memories, like the associations examined here.

That latter point makes the last sentence of the paper a bit over the top, as the authors suggest that a chemical that enhances protein kinase M ζ activity might make for a good treatment for memory disorders like amnesia and age-related decline. Until we have a clearer sense of how many types of memories it works for, that’s a bit premature. Fortunately, there are lots of ways to test the recall abilities of animals, many of which don’t involve negative associations. Hopefully, testing of the virus’ more general impact on memory is already underway.

Image: HIV (green dots), a member of the lentivirus genus. (C. Goldsmith/P. Feorino/E. L. Palmer/W. R. McManus/CDC)