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Scientists can now delete and fabricate memories in mice. Are humans next?

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Inside laboratories, memory researchers are doing crazy things to the brains of mice and rats. They're deleting memories, putting them back in, and even making the rodents remember things that never even happened.

But these aren't just perverse experiments. They're attempts to better understand memory, which is at the root of some of today's most important health problems — including Alzheimer's and post-traumatic stress disorder. If researchers can figure out how memory really works, they might be able to better help people with these problems.

The big caveat here is that most of these wild experiments are still being done on rodents — which are very different from people. And the experiments require sophisticated genetic engineering techniques that may not ever work on us. There's no guarantee that scientists will be able to delete human memories (or implant false ones) in quite the same way.

Even so, these experiments are teaching us a lot about how memory works, which could well lead to other therapies that build upon that knowledge. 

How to delete memories in mice — and then bring them back

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Researchers have gotten very good at deleting memories in mice. This is essentially the Eternal Sunshine of the Spotless Mind scenario — in which people had memories of their lost loves erased in order to gain peace of mind.

Here's how it works in real life. Scientists have already shown that they can broadly weaken or wipe out a rodent's memory with several drugs, including one that inhibits PKMzeta — a molecule thought to naturally strengthen connections between brain cells, which is one way that memories are thought to form.

But more recently, researchers have been trying to delete specific memories, rather than do a complete wipe. And they've had some success. For example, scientists have found that when they send the drug Latrunculin A into a rat's amygdala brain region, which deals with emotions, they can selectively erase certain memories (say, erasing a learned preference for a room where the rat has used meth in the past) but leave other memories intact (like memories of getting shocked).

Then, in June 2014, researchers at the University of California at San Diego published a paper in Nature showing that they could delete (and later restore) a very specific memory in a rat by stimulating its memory-holding cells at specific frequencies.

How did they do this? First, they genetically modified certain neurons in the rat's brain to make them sensitive to light — so that the researchers could activate them with an optical fiber shining into the brain. (This is called optogenetics.) They then subjected the rat to mild electric shocks while turning those neurons on. Later on, activating those neurons led the rat to show a fear response — a sign that an unpleasant memory had been implanted.

The scientists then subjected the rat's brain to light pulses at a low frequency, which weakens connections between neurons. That destroyed the memory of the electric shock. And when they subjected the rat to high-frequency pulses, which strengthens connections, the memory came back. "We were playing with memory like a yo-yo," the lead author Roberto Malinow, a neuroscientist at the University of California, San Diego, told Nature News.

Could this work on humans? If scientists could someday locate the neurons that hold a specific memory within the human brain, it's possible that they could weaken the connection between these cells in order to destroy it — say, by stimulating them at a low frequency using electrical pulses or magnetic pulses. (This wouldn't require any genetic engineering, but it might require surgery.)

The big challenge would be finding the memory in the first place and then finding a way to target those particular cells precisely. This is certainly far beyond the capabilities of what scientists can do with a living human brain today.

How to change a bad memory into a good one
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The big downside of erasing memories altogether is that it's sort of creepy. Our memories, after all, make us who we are. So what if instead of deletion, we could modify memories slightly so that they didn't have as many negative connotations? This might be a huge help to people with PTSD, for instance.

This, too, has been done in rodents. In a study published in August 2014 in Nature, researchers took negative or positive memories in mice and switched them to have the opposite emotion. (The group, led by Susumu Tonegawa at MIT, has also created false memories in mice using similar techniques, but that's another story for another day.)

How did this work? First, they gave the mice a negative memory of a certain location by associating it with a mild electric shock. At the same time, they used genetic techniques to "label" the brain cells that were forming memory during this specific period of time.

Later on, the researchers modified the emotional feel of the memory by activating those specific brain cells while giving the mouse a positive experience (putting a female mouse nearby). That seems to have worked. Initially, the mouse had avoided the scary location in question — because of the association with electric shocks. But after the memory modification, the mouse seemed attracted to the place.

Why would people want to change their own memories?

There are lots of possible benefits of someday being able to delete or modify memories. For example, bad memories of traumatic experiences can haunt people, causing serious mental health problems and contributing to PTSD. And, even at a non-clinical level, bad memories can still create serious distress.

Conversely, turning good memories into bad ones (or deleting them altogether) might also be useful. Consider someone who's trying to fight a drug addiction. Many of these people form positive associations between locations, people, and objects associated with drug use. These things can then end up producing drug cravings all by themselves. Being able to transform some of those positive associations into distasteful ones might help fight addiction.

Therapists already try to retrain problematic associations through some cognitive-behavioral therapy techniques and other treatments. But PTSD and some addictions can still be quite difficult to treat in many people. So it's possible that memory modification may, one day, be able to help.

Further reading: Recently some researchers have been working to influence the human brain with non-invasive techniques such as transcranial magnetic stimulation, which doesn't require any surgery.

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