It’s the premise of every third sci-fi thriller. Man wakes up to his normal seeming life, but of course it isn’t. At first, just the little things are off – the dog won’t eat and the TV keeps looping some strange video – but whatever. A few cuts later, with only his granddad’s rusty brass knuckles and a steely-eyed contempt for authority, our hero reveals a conspiracy that kicks up straight to the top. There were deals. Some blackmailing. A probe or two. But in the end, what’s most important is that everything he thought he knew was wrong. Because the scientists (Noooo!!) got to him with one of those electrode caps and rewrote his memory. Everything – the job, the daughter, the free parking – is a lie.
The dramatic ploy works on us because memory seems inviolable, or at least, we desperately hope that it is. We allow that our memories may fade and fail a bit, but otherwise, we go on the sanity-preserving assumption that there is one reason why we remember a particular thing: because we were there, and it actually happened.
Now, a new set of experiments, led by MIT neuroscientists Steve Ramirez and Xu Liu in Susumu Tonegawa’s lab, shows that this needn’t be the case. Using a stunning set of molecular neuroscience techniques (no electrode caps involved), these scientists have captured specific memories in mice, altered them, and shown that the mice behave in accord with these new, false, implanted memories. The era of memory engineering is upon us, and naturally, there are big implications for basic science and, perhaps someday, human health and society.
Although the techniques these investigators used to manipulate memory involved a jaw-dropping sampling from modern neuroscience’s bag of tricks, the essential strategy is easy to understand. Basically, you need a way of labeling neurons that were active during a specific experience, and a switch to operate them.
Enter designer mice. The mice in Ramirez and Liu’s experiments had been genetically modified so that when their neurons were highly active (and therefore presumably encoding ongoing experiences) those same neurons would produce a molecular label, as well as a molecular ‘ON’ switch. The label caused the neurons to glow red, and the switch was the now famous, and likely-future-Nobel-landing molecule Channelrhodopsin, which renders neurons light-activated. In these mice, then, the scientists could quite literally see recent experiences that had been written to specific brain cells. Even more impressively, they could activate those very same neurons in behaving mice by shining light on them, re-awakening whatever fragments of experience those cells had presumably encoded.
A final, and key feature of Ramirez et al’s labeling system was that it could itself be switched on or off, under control of the common antibiotic doxycycline. If doxycyline was given to the mice in their diet, the labeling process was snuffed out. If doxycycline was removed though, labeling was unimpeded. This was critical for labeling memories formed only during specific, experimenter-defined time windows.
In their main experiment, the researchers removed doxycycline for a short spell as mice explored a novel arena, allowing the neurons representing that arena –especially those neurons in a brain area called the hippocampus – to become labeled and light-activatable. The mice were then given doxycycline again to stop the labeling process. In this way, the experimenters had given themselves a literal biological handle on something that seems hopelessly subjective: a mental representation of a particular experience, at a particular time.