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Researchers say that using optogenetics to artificially reactivate memories could advance the study of neurodegenerative disorders.
A transgenic mouse hippocampus. (Credit: Nikon Small World Gallery) In a famous surgery in the early 1900s, Canadian neurosurgeon Wilder Penfield, trying to treat epilepsy, found that stimulating specific neurons while patients were under local anesthesia caused them to vividly recall complex events. The mind, then, is based on matter, Penfield concluded.
Now researchers at MIT say they put this observation to the test in a rigorous study showing that the direct reactivation of specific hippocampus neurons can lead to very specific memory recall. And to do this, all they used was light.
"We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells -- in this case by light," Susumu Tonegawa, a biology and neuroscience professor at MIT, Nobel laureate and lead author of the study, said in a news release.
For the study, published online today in the journal Nature, researchers used optogenetics, a technique that combines optical and genetic methods to control specific events in specific cells. (The tech was co-invented by MIT's Ed Boyden, who last year proposed using optogenetics to induce light sensitivity in the retina and ultimately restore sight in the blind.)
Using optogenetics to stimulate memory, the researchers first learned which brain cells in the hippocampus were active in a mouse exploring a new environment. They then coupled the genes activated in those brain cells with the genes for channelrhodopsin-2 (ChR2), a light-activated protein used in optogenetics.
"We wanted to artificially activate a memory without the usual required sensory experience, which provides experimental evidence that even ephemeral phenomena, such as personal memories, reside in the physical machinery of the brain," said co-author Steve Ramirez, a graduate student in Tonegawa's lab.
The team then used tiny optical fibers to pulse light to neurons with this genetic couplet so that, by seeing the neurons associated with experiential learning light up, they could tag the physical network of neurons associated with a specific memory.
Their final step was to observe mice entering an environment, deliver a mild shock to their feet to teach the mice to fear the environment, tag the brain cells that were activated with ChR2, and then expose only those brain cells to pulses of light in a totally different environment. Sure enough, the mice assumed defensive, immobile crouches -- a sign that they were recalling the fear they experienced in the initial environment.
These findings are only preliminary, but the researchers believe that this light-induced fear demonstrates that the mice were remembering the shocks from a different time and place, and that light alone artificially re-activated that specific memory by stimulating the neurons they had tagged.
Tonegawa says their findings call into question Descartes' declaration that the mind is distinct from the body and cannot be studied as a natural science: "He was wrong. This experimental method is the ultimate way of demonstrating that mind, like memory recall, is based on changes in matter."
The researchers suggest that their method could advance the study of neurodegenerative and neuropsychiatric disorders. "The more we know about the moving pieces that make up our brains," said grad student Ramirez, "the better equipped we are to figure out what happens when brain pieces break down."
