It was first thought that when memories are stored, or consolidated into a long-term stable form, they are resistant to disruption. Much of the focus in memory research has been on identifying the molecules involved in this storage process. But, it then became clear that when one of these long-term stable memories is reactivated, it can return to an unstable state and again be vulnerable to disruption. A wave of studies then focused on how to re-stabilize a memory after it had been reactivated. Now, a recent study in Science by Reut Shema and colleagues from the Weizmann Institute of Science in Israel has shown that by inhibiting one very specific enzyme,PKMζ, a memory can still be disrupted long after it has been formed, even when it is not reactivated first. PKMζ has been previously implicated in maintaining memories in the brain area involved in forming memories, the hippocampus, but its role in the brain area involved in storing memories, the neocortex, was not known.

The team trained rats to dislike a certain taste by pairing the taste with a lithium chloride injection, which results in the rats being sick. This procedure, conditioned taste aversion, is similar to the effect experienced by those unfortunate individuals who have had food poisoning. The learned`dislike' is rapidly learned and long remembered. After aversion training, the authors injected an inhibitor of PKMζ, ZIP, into the insular cortex, an area believed to store taste memories. Rats demonstrated no memory for the learned dislike 1 week or 1 month later.

Having shown that ZIP inhibits memory directly after learning, the authors wanted to know whether ZIP can disrupt the memory after it has been formed and stored. They repeated the experiment but now injected ZIP 3, 7 or 25 days after aversion training. Regardless of when ZIP was injected, rats again demonstrated no memory for the aversion training. Thus, despite what is traditionally thought in learning theory, there was no closure of the consolidation window, which is the time frame when memories are stored, making them long-term and stable. In addition, the memory did not need to be reactivated first to make it vulnerable. Persistence of memory is thus dependent on the ongoing activity of this enzyme long after the memory is considered to have consolidated into a long-term stable form.

The effects of these experiments seem irreversible suggesting that PKMζ permanently maintains long-term taste memories in the insular cortex. The role of PKMζ in maintaining other types of memories in other areas of the neocortex remains to be determined. Even though it is difficult to prove the absence of memory it seems that the authors managed to permanently erase the memory for the learned dislike. This offers hope for those who would like unwanted memories erased. But, as an unfortunate sufferer of food poisoning, I think I would like to keep the memory of that particular restaurant that ruined my holiday weekend.

Shema, R., Sacktor, T. C. and Dudai, Y. (
). Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMζ.