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Optogenetic Method Erases, Reactivates Memories

SAN DIEGO, June 2, 2014 — A new light-based technique could essentially control memories, showing potential for treating brain-related conditions such as Alzheimer’s disease.

A team from the University of California, San Diego, has discovered how to use optogenetics to deactivate and then reactivate memories in the brains of genetically engineered rats. This is the first evidence demonstrating that this can be done by stimulating nerves in the brain via synapsis.

“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,” said Dr. Roberto Malinow, professor of neurosciences at UCSD.

In the study, the researchers optically stimulated a group of neurons in rats’ brains while also dispensing electric shocks. The animals learned to associate pain with that stimulation, subsequently displaying fear behavior when it happened again.

Analysis showed chemical changes within those synapses, which the researchers said is indicative of synaptic strengthening.

In further testing, the same nerve group was stimulated with low-frequency optical pulses. This appeared to weaken the circuitry. In turn, the rats no longer responded with fear to the stimulation. This method, called reverse long-term potentiation (LTP), shows that the memories of that pain association were erased, the researchers said.

The researchers further discovered that by using memory-forming, high-frequency optical pulses to restimulate the same nerves that were originally tested, they were able to reactivate those lost memories.

“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 Dr. Sadegh Nabavi, a postdoctoral researcher at UCSD and the lead author on the study.

The findings could be applied to the treatment of Alzheimer’s disease, in which beta amyloid peptide accumulates in the brain and weakens synaptic connections — similar to the way in which the low-frequency stimulation erased the rats’ memories.

“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,” Malinow said.

The work was funded by the National Institutes of Health and the Cure Alzheimer’s Fund. The research was published in Nature (doi: 10.1038/nature.2014.15330).

For more information, visit www.ucsd.edu.


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