The movie Inception is getting closer to reality. By planting false memories into the minds of mice, neuroscientists at MIT have created the first artificially implanted memories. And they've brought us closer to understanding the fallibility of human recollection.
When we experience something, say a trip to the park, a memory of the event is stored in a constellation of interconnected neurons in our brains called an "engram," or memory trace. When you recall that trip to the park, neurons in the engram become active. Reactivate those neurons artificially, the theory goes, and you can bring the memory bubbling to the surface of someone's psyche.
In the 1940s, Canadian neurosurgeon Wilder Penfield delivered electrical shocks to the temporal lobes of patients about to undergo brain surgery, and his subjects reported the sudden recollection of specific memories. While Penfield's methods were too crude to isolate a single engram, they provided more evidence for the memory-trace hypothesis. And they also pointed to a brain region, the temporal lobe, as a repository for episodic memories. Today, we know that these memories are actually stored in a sea-horse shaped region of the temporal lobe called the hippocampus.
In a study published in the latest issue of Science, a team of researchers led by MIT neuroscientist and Nobel Laureate Susumu Tonegawa demonstrates its ability to isolate and activate engrams in a mouse's memory-rich hippocampus. The researchers go on to implant false memories in the mouse's mind, causing it to recall experiences that have never actually occurred. Here's how they did it.
First, Tonegawa and his team genetically engineered mice capable of expressing a protein called Channelrhodopsin-2 (ChR2). Importantly, the protein was expressed exclusively in the hippocampus, and only in neurons involved in memory formation. This allowed Tonegawa and his team to effectively label only the brain cells encoding for a specific engram. Place a mouse in a safe environment (Chamber A, the blue box above), and the brain cells encoding for the memory of this environment express ChR2 (the white dots).
Here's the brilliant bit. ChR2 is a light-sensitive protein; shine a light on it with the tip of an optical fiber that's been securely implanted in the brain, and cells that express it become activated. The technique – known as "optogenetics" – is among the most useful to emerge in the field of neuroscience in recent memory, and Tonegawa and his colleagues use it here to great effect. By placing the animal in a second, entirely different environment (Chamber B, the red box) and delivering light to the hippocampus, the researchers could reactivate the engram established in Chamber A, forcing the mouse to recall its experience while situated in the entirely novel environment of Chamber B.
Next comes the memory implantation. While the mouse is busy recalling the first environment, the researchers deliver a mild electrical shock to the rodent's feet. The shock conditions fear into the mouse. Past research has shown that if one shocks a mouse in a specific environment frequently enough, it will freeze in trepidation when reintroduced to the environment at a later date. But what happens when a mouse in one environment is shocked while recalling a different, previous environment – one in which it received no foot shock?
Incredibly, when Tonegawa and his colleagues placed the mouse back into Chamber A, it stopped in its tracks, evincing behavioral signs of fear. The mouse's reaction indicates it had formed a false fear-memory associated with Chamber A while standing in Chamber B. A false memory had been successfully incepted by manipulating the very neural connections involved in the mouse's true memory. Mice later placed in Chamber B also froze in their tracks, though not as readily as those that had been shocked in Chamber B without having their memory of Chamber A activated.
"Now that we can reactivate and change the contents of memories in the brain, we can begin asking questions that were once the realm of philosophy," said study co-author Steve Ramirez in a statement. He added:
Are there multiple conditions that lead to the formation of false memories? Can false memories for both pleasurable and aversive events be artificially created? What about false memories for more than just contexts — false memories for objects, food or other mice? These are the once seemingly sci-fi questions that can now be experimentally tackled in the lab.
If Ramirez's study sounds familiar, don't worry; you don't have an implanted memory of it. A study published last year by Aleena Garner and her colleagues at UC San Diego followed a very similar experimental protocol, but failed to see increased freezing in mice re-exposed to either Chamber A or Chamber B. Instead, the mice are believed to have formed what Garner and her team call a "hybrid" memory, one that could only be retrieved by combining "elements of both the... artificial stimulation and the natural sensory cues from the [fear-conditioning environment.]" If either condition were presented independently, the mice would carry on about their business — as though they had forgotten to be afraid.
"A key difference in [Garner's system]," write Ramirez and Xu Liu, first authors on the present paper, is that "cells in the entire forebrain were labeled and reactivated over an extended period by a synthetic ligand." Ramirez and Liu therefore hypothesize that activating neurons across larger areas of the brain and for longer periods of time may favor the formation of a memory "which may not be easily retrievable by the cues associated with each individual memory." In contrast, they argue, activating smaller populations of neurons for shorter periods of time "may favor the formation of two distinct (false and genuine) memories," as observed in the present study.
"Whether it's a false or genuine memory," said Tonegawa in a statement, "the brain's neural mechanism underlying the recall of the memory is the same." Ramirez expands on his colleague's point:
These kinds of experiments show us just how reconstructive the process of memory actually is. 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.
Understanding how memories – false or otherwise – form in the first place could help us understand why human recollection is so untrustworthy.
The researchers' findings are published in the latest issue of Science.