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Alzheimer's Answer? Researchers Erase, Re-Create Memories in Rats

First Posted: Jun 01, 2014 06:37 PM EDT
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Doctors in the future may be able to restore the memories of individuals who have lost them, perhaps the result of a debilitating injury or condition, such as Alzheimer's disease.

That, at least, is the expectation of researchers at the University of California, San Diego School of Medicine who report erasing and then reactivating memories in rats, thereby altering the animals' reactions to past events.

Published in the June 1 advanced online issue of the journal Nature, the study is the first to demonstrate the ability to selectively remove a memory and then reactivate it by stimulating nerves in the brain.

"We can form a memory, erase that memory and we can reactivate it, at will, by applying a stimulus that selectively strengthens or weakens synaptic connections," Roberto Malinow, a professor of neurosciences and the research's senior author, said in a university news release.

Scientists optically stimulated a group of nerves in a rat's brain that were genetically modified to make it sensitive to light -- and, at the same time, delivered an electrical shock to the animal's foot.

The rats involved in the study quickly learned to associate the optical nerve stimulation with pain and, as a result, acted fearfully whenever the particular nerves were stimulated.

Analyses traced chemical changes within the optically stimulated nerve synapses, which was evidence of synaptic strengthening.

During the next stage of the study, the researchers were able to weaken the synaptic circuitry by stimulating the same nerves with a memory-erasing, low-frequency series of optical pulses.

After the pulses were administered, the rats who had previously learned to respond in fear to the original nerve stimulation no longer responded to the optical stimulation with fear, an apparent sign the memory associated with pain had been erased.

Equally remarkable, if not more so, was that the scientists discovered they could re-activate the lost memory by re-stimulating the same nerves with a high-frequency series of optical pulses -- after which the re-conditioned rats again responded to the original stimulation in fear, even though their feet had not been re-shocked.

"We can cause an animal to have fear and then not have fear and then to have fear again by stimulating the nerves at frequencies that strengthen or weaken the synapses," said Sadegh Nabavi, a postdoctoral researcher in Malinow's lab and the study's lead author.

Malinow noted that the beta amyloid peptide, or string of molecules, that accumulates in the brains of people with Alzheimer's disease weakens synaptic connections in much the same way the low-frequency stimulation erased memories in the rats.

"Since our work shows we can reverse the processes that weaken synapses, we could potentially counteract some of the beta amyloid's effects in Alzheimer's patients," said Malinow.

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