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Drug found to erase memories in rats

Aug. 16, 2007
Special to World Science  

In the comedic sci­ence-fic­tion film “Men in Black,” a top-se­cret team uses a “mem­ory eraser” to make peo­ple for­get they’ve seen aliens. Mem­o­ry eras­ure is a re­cur­rent theme in sci­ence fic­tion, but un­til re­cently it has stayed in that realm on­ly.

That’s chang­ing. For the first time, re­search­ers say they have erased spe­cif­ic mem­o­ries in rats weeks af­ter the me­mor­ies were formed. 

The find­ing comes on the heels of an­oth­er study a year ago in which sci­en­tists erased one-day old mem­o­ries of spa­tial in­forma­t­ion from rats. But it was un­known then wheth­er that could work for more es­tab­lished or com­plex mem­o­ries, the sci­en­tists said; now it’s be­com­ing ap­par­ent that it can.

The find­ings can serve to ben­e­fit peo­ple, such as for treat­ments to en­hance mem­o­ry or erase trau­mat­ic rec­ol­lec­tions, the re­search­ers added. But some au­thors have al­so pre­dicted po­ten­tial for abuse of such treat­ments. For in­stance, one might blot out a mem­o­ry to keep some­one from test­i­fy­ing about a crime. “Only the inherent good­ness of our fel­low men and wo­men” can pre­vent abuse, wrote one of the sci­ent­ists, Todd Sack­tor of SUNY Down­state Med­i­cal Cen­ter in Brook­lyn, N.Y., in an email.

Sacktor is part of a team—along with Yadin Du­dai of the Weiz­mann In­sti­tute of Sci­ence in Re­hovot, Is­ra­el—of researchers stu­dying what hap­pens in our brains when we learn and re­mem­ber. Mem­o­ries aren’t recorded as a sta­ble phys­i­cal change, like writ­ing an in­scrip­tion on a clay tab­let, they have found. Rath­er, long-term mem­o­ry stor­age is a dy­nam­ic pro­cess, in­volv­ing a min­ia­ture mo­lec­u­lar ma­chine that must run con­stantly to keep mem­o­ries alive. Jam­ming the ma­chine briefly can erase long-term mem­o­ries, they say. 

In their new stu­dy, to ap­pear in the Aug. 17 is­sue of the re­search jour­nal Sci­ence, they trained rats to avoid cer­tain tastes. They then in­jected in­to the taste cor­tex—a brain ar­ea linked to taste mem­o­ry—a drug that would block the ac­tions of a par­ti­cu­lar mol­e­cule. They hy­poth­e­sized, based on ear­li­er re­search, that this mol­e­cule is a min­ia­ture mem­o­ry “ma­chine” that keeps mem­o­ry up and run­ning. 

The mol­e­cule is an en­zyme called PKMzeta. An en­zyme is a pro­tein mol­e­cule that causes changes in oth­er pro­teins. PKMzeta lies in synaps­es, con­tact points be­tween nerve cells where they pass mes­sages to each oth­er in the brain. The en­zyme causes the struc­ture of these con­tacts points to change sub­tly.

But the mol­e­cule must be per­sist­ently ac­tive to main­tain this change, re­searchers found. Learn­ing brings about this ac­ti­vity. Si­lenc­ing PKMzeta re­verses the change: re­gard­less of the taste the rats were trained to avoid, they for­got their learn­ed aver­sion af­ter one in­ject­ion of the drug.

The tech­nique worked as suc­cess­fully a month af­ter the mem­o­ries were formed, equiv­a­lent to years for a hu­man, the re­search­ers said. All signs so far in­di­cate that the un­pleas­ant mem­o­ries were gone, they added. “This drug is a mo­lec­u­lar ver­sion of jam­ming the opera­t­ion of the ma­chine,” said Du­dai. “When the ma­chine stops, the mem­o­ries stop.”

In a pre­vi­ous study in the Aug. 25, 2006 Sci­ence, a group in­clud­ing Sack­tor  found that a si­m­i­lar treat­ment could erase one-day-old mem­o­ries of spa­tial in­forma­t­ion in rats. But this work, re­search­ers said, shed lit­tle light on PKMzeta ac­ti­vity in the neo­cor­tex, the brain re­gion con­sid­ered re­spon­si­ble for per­ma­nently stor­ing most long-term mem­o­ries. These in­clude mem­o­ries re­quired for higher-level cog­ni­tive func­tions, such as lan­guage and com­plex thought. The new work fo­cused on that ar­ea of the brain.

Yiv­sam Az­gad, a spokes­man for the Weiz­mann In­sti­tute, wrote in an e­mail that he thinks abuse of the find­ings can be pre­vent­ed only through “eth­ics, and by the laws of each coun­try.” As with all re­search, he added, it’s sci­en­tists’ job to gain new knowl­edge, and so­ci­ety’s to use it re­spon­si­bly.

* * *

In the science-fiction movie Men in Black, a top-secret team uses a “memory eraser” to make people forget that they’ve seen aliens. Memory erasure is a recurrent theme in science fiction, but until recently it has stayed in the realm of fiction only. That’s changing. For the first time, researchers say they have erased specific memories in rats weeks after they were formed. The finding comes on the heels of another study a year ago in which scientists erased one-day old memories of spatial information from rats. But it was unknown then whether it could work for more established and more complex memories, the scientists said; now it’s becoming apparent that it can. The findings could be used to benefit people, such as for treatments to enhance memory or erase traumatic recollections, the researchers added. But some authors have also predicted potential for abuse of such treatments; for instance, someone might erase a memory crucial to prosecuting a crime. Yadin Dudai, a neurobiologist at the Weizmann Institute of Science in Rehovot, Israel, and colleagues have been studying what happens in our brains when we learn and remember. Memories aren’t recorded as a stable physical change, like writing an inscription on a clay tablet, they found. Rather, storing long-term memories is a much more dynamic process, involving a miniature molecular machine that must run constantly to keep memories alive. Jamming the machine briefly can erase long-term memories, they found. In their new study, to appear in the Aug. 17 issue of the research journal Science, they trained rats to avoid certain tastes. They then injected a drug to block the actions of a molecule into the taste cortex, an area of the brain associated with taste memory. They hypothesized, on the basis of earlier research, that this molecule is a miniature memory “machine” that keeps memory up and running. The molecule is an enzyme called PKMzeta. An enzyme is a protein molecule that causes structural and functional changes in other proteins. PKMzeta is located in the synapses—the functional contact points between nerve cells, where they pass messages to each other in the brain. This changes the structure of these contacts points subtly. But the molecule must be persistently active to maintain this change, they found; learning brings about this activity. Silencing PKMzeta, reasoned the scientists, should reverse the change. This is what they found: Regardless of the taste the rats were trained to avoid, they forget their learned aversion after a single application of the drug. The technique worked as successfully a month after the memories were formed, the researchers said. A month for a rat is equivalent to years for a human, they noted. All signs so far indicate that the affected unpleasant memories of the taste had indeed disappeared, they said. “This drug is a molecular version of jamming the operation of the machine,” said Dudai. “When the machine stops, the memories stop as well.” In a previous study in the Aug. 25, 2006 Science, a group including Dudai colleague Todd C. Sacktor of SUNY Downstate Medical Center in Brooklyn, N.Y. found that a similar treatment could erase one-day-old memories of spatial information in rats. But this left little known about PKMzeta activity in the neocortex, the part of the brain thought to be responsible for permanently storing most long-term memories, the researchers said. These include memories required for higher-level cognitive functions, such as language and complex thought. The new work focused on that area of the brain. In their studies, the researchers didn’t delve into the the issues of how to prevent possible abuse of the findings. Dudai was unavailable for comment; an email was sent to Sacktor requesting his comments on the subject. Yivsam Azgad, a spokesman for the Weizmann Institute, wrote in an email that “the only ways of preventing the abuse of this type of knowledge are through human ethics, and by the laws of each country.” As with all research, he added, it’s the scientists’ job to gain new knowledge, and society’s to use it responsibly.