Gone in a ZIP: researchers erase long-term memories with chemicals

By John Timmer

It might be time to forget a lot of what you remember about memory. Although transient memories are largely the product of chemical processes in the neurons of the brain, it has been thought that the long-term consolidation of memories involves permanent changes. Proposals for this long-term storage include prion-like alterations in protein structures and rewiring of the connections among brain cells. But a study appearing in today's issue of Science suggests that memories remain a transient chemical property of the brain even weeks after they're formed.

A lot of work had shown that a protein called protein kinase M zeta (PKMζ) was involved in the consolidation of a subset of memories. The authors of the new article decided to see if memories of aversive tastes were among them. They introduced rats to a new taste (saccharine) and then injected them with a nausea-inducing salt. Normally, the rats remember the taste and avoid anything with saccharine in it. Injections of a PKMζ inhibitor called ZIP into the brain's cortex a few days after, while memory consolidation might still be in progress, blocked the formation of long-term memories. The rats would happily drink saccharine-laced water, despite the earlier bout of nausea.

This was all pretty consistent with past results. But then the authors performed an experiment that I can only assume was expected to act as a control: they injected ZIP at one week and at 25 days. The surprising result was that these later injections worked just as well as the earlier one had. By 25 days, a memory is generally considered as permanent as they get, yet a dose of ZIP in the cortex erased the averse association from the rats' minds. Testing for several weeks afterwards suggested that, once gone, these memories never come back.

The team went on to perform a set of experiments that, depending on your perspective, are either fascinating or disturbing. Some rats were put through two rounds of aversion training, followed a week later by a test that showed they found saccharine repellent. One day later, a single injection of ZIP eliminated the aversion. One dose of ZIP could also eliminate aversion from two different chemicals, memorized two days apart.

It's hard to tell what the limits of ZIP-mediated memory erasure are, given that the test subjects are rats. There were some things it did not affect, though. Rats are normally hesitant about unfamiliar tastes, a hesitancy that goes away with familiarity. Hitting the cortex with ZIP was unable to eliminate this sense of familiarity.

It's pretty hard to square these results with any general models of memory consolidation that involve permanent structural changes in the brain. Structural changes may still play a role—it's technically possible that different areas of the brain store memories in a different manner—but it's not clear why the brain would need more than one way of approaching the same problem.

Before you get excited about the idea of wiping every past rejection out of your mind, please remember that the procedure involves jabbing needles into your cortex, and there's absolutely no way to control the process. You're just as likely to lose your aversion to stepping off the curb and into rush-hour traffic.