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Inception: Artificial memories implanted in mice

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August 1, 2013

MIT neuroscientists identified the cells (highlighted in red) where memory traces are stor...

MIT neuroscientists identified the cells (highlighted in red) where memory traces are stored in the mouse hippocampus (Photo: Steve Ramirez and Xu Liu / MIT)

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An ongoing collaboration between the Japanese Riken Brain Science Institute and MIT’s Picower Institute for Learning and Memory has resulted in the discovery of how to plant specific false memories into the brains of mice. The breakthrough significantly extends our understanding of memory and expands the experimental reach of the new field of optogenetics.

The ability to learn and remember is a vital part of any animal's ability to survive. In humans, memory also plays a major role in our perception of what it is to be human. A human is not just a survival machine, but also reads, plans, plays golf, interacts with others, and generally behaves in a manner consistent with curiosity and a need to learn.

Forgetting where we put the keys is a standard part of the human condition, but in the last few decades our knowledge of more serious memory disorders has grown rapidly. These range from Alzheimer's disease, where the abilities to make new memories and to place one's self in time are seriously disrupted, to Post-Traumatic Stress Disorder, in which a memory of a particularly unpleasant experience cannot be suppressed.

Such disorders are a powerful force driving research into discovering how healthy memory processes function so that we can diagnose and treat dysfunctional memory function.

In previous work, the team of researchers at the Picower Center for Neural Circuit Genetics were able to identify an assembly of neurons in the brain's hippocampus that held a memory engram, or data concerning a sequence of events that had taken place previously. In recalling a memory, the brain uses this data to reconstruct the associated events, but this reconstruction generally varies slightly to substantially from what actually occurred.

The researchers were able to locate and identify the neurons encoding a particular engram through the use of optogenetics. Optogenetics is a neuromodulation technique that uses a combination of genetic modification and optical stimulation to control the activity of individual neurons in living tissue, and to measure the effects of such manipulation.

The MIT team genetically engineered the hippocampal cells of a new strain of mouse so that the cells would form a light-sensitive protein called a channelrhodopsin (ChR) that activates neurons when stimulated by light. This involved engineering the mice to add a gene for the synthesis of ChR, but that gene was also modified so that ChR would only be produced when a gene necessary for memory formation was activated. In short, only neurons actively involved in forming memories could later be activated by light.

Initial work using the genetically engineered mice focused on determining what neurons in the hippocampus are associated with forming a new, specific memory. There were at least two schools of thought on how memory engrams were stored – locally or globally. They discovered that a memory is stored locally, and can be triggered by optically activating a single neuron.

"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,” says lead author Steve Ramirez.

The new results came from a chain of behavioral experiments. The researchers identified the set of brain cells that were active only when a mouse was learning about a new environment. The genes activated in those cells where then coupled with the light-sensitive ChR.

These mice were then exposed to a safe environment in a first box, during which time the neurons which were actively forming memories were labelled with ChR, so they could later be triggered by light pulses.

Next the mice were placed in a different chamber. While pulsing the optically active neurons to activate the memory of the first box, the mice were given mild foot shocks. Mice are particularly annoyed by such shocks, so this created a negative association.

When the mice were returned to the first box, in which they had only pleasant experiences, they clearly displayed fear/anxiety behaviors. The fear had falsely become associated with the safe environment. The false fear memory itself could be reactivated at will in any environment by triggering the neurons associated with that false memory.

Cartoon of the MIT-Riken experiment. In the left-hand box, the mouse learns the safe envir...

“Remarkably, the recall of this false memory recruited the same fear centers that natural fear memory recall recruits, such as the amygdala,” says Xu Liu, a post-doctoral fellow and co-first author of the study. The recall of this false memory drove an active fear response in associated parts of the brain, making it indistinguishable from a real memory. “In a sense, to the animal, the false memory seems to have felt like a ‘real’ memory,” he said.

These kinds of experiments show us just how reconstructive the process of memory actually is,” said Steve Ramirez, a graduate student in the Tonegawa lab and the lead author of the paper. “Memory is not a carbon copy, but rather a reconstruction, of the world we've experienced. Our hope is that, by proposing a neural explanation for how false memories may be generated, down the line we can use this kind of knowledge to inform, say, a courtroom about just how unreliable things like eyewitness testimony can actually be." Perhaps they can also provide a solution for the problem of lost keys.

Sources: MIT and Riken

About the Author
Brian Dodson From an early age Brian wanted to become a scientist. He did, earning a Ph.D. in physics and embarking on an R&D career which has recently broken the 40th anniversary. What he didn't expect was that along the way he would become a patent agent, a rocket scientist, a gourmet cook, a biotech entrepreneur, an opera tenor and a science writer.   All articles by Brian Dodson
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4 Comments

At some time in the far off future, after mans reign was done, the immortal, invulnerable, super intelligent race of mice, waited for infinity to show its so called end, these mice were born in labs everywhere on earth, and when man was gone, they found each other. when the great crystal ships arrived a million centuries later, and found the mice, they were amazed at their inception, and took them off the now desolate planet earth. man kinds mark, he left in his dust, the mice who endured all received all, as it said in the book as it lay tattered, blowing open in the harsh dry wind, in the end the meek shall inherit the earth............

science ninja
2nd August, 2013 @ 09:52 am PDT

Getting deliciously close to the prospect of downloading data into the brain.

In the next decade we might even be able to download the library of congress into some poor soul's head. Though I don't know if that will make him more interesting to talk to. Some dry material there :b

I'm not much for false memory but I would think the same technique could be used to implant knowledge combined with experience and emotions of fulfillment whenever this knowledge is applied.

Empower people to get off their asses and apply themselves.

The only burden of this tech is the social implication. If 90% of people have the means and will to become doctors and lawyers, then who will want to scrub the toilets, wash the floors and fix the taps when they leak. We cant afford to over specialise or it will destroy our species? The answer might be emergence of mandatory mixed duty roles or rotating rosters. Drones and robots will fill in the tedious leftover bits.

Nairda
2nd August, 2013 @ 06:30 pm PDT

I would prefer that only simulated mice were used (not real mice) and for that we need to learn how to simulate full bio-dynamics right to the gene expression level and then all this research could be done much faster and even reach far into the future of real world possibilities and application for intercepted bio-dynamics with full repercussions simulations too and save all the waste that is occurring with animals and then mistakes due to be seen in retrospect. (Also, an intelligent being here mentioned that the mice didn't ask for it. ) Consider ecosystems (enhanced ecosystems) as the right physical place to improve live species - not labs! Evolution may have potential that better things are in store for species too.

Ahimsa Fruitarian
3rd August, 2013 @ 10:25 pm PDT

Mice today, serfs next year! Make somebody 'know' they are now a slave, soldier, suicide bomber - what could go wrong? Dictators and oppressors the world over are salivating already.

The Skud
4th August, 2013 @ 07:59 pm PDT
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