Did that Actually Happen?: Shedding Light on False Memories

by Manisha Kintali

In 1994, Elizabeth Loftus, a cognitive psychologist, was able to implant into a quarter of her subjects a memory of being lost and in panic in a mall as a child and eventually being rescued by an elderly person who reunited them with their parent. This experiment was purely psychological, but is it possible to actually implant a memory of this nature physiologically? These types of experiments call to mind certain popular films like Inception, but a study conducted this past summer might be just as mind-bending and fascinating. In July of 2013, Steve Ramirez and Xu Liu from the MIT lab of Susumu Tonegawa, a 1987 Nobel Prize winner for Medicine or Physiology, were able to successfully create false memories in the hippocampus of mice. False memories are memories of events that never actually happened or distorted memories resulting from the influence of external events or the feeding of new, suggestive information.

“What if we can start off by going into the brain and finding a single memory to begin with? Can we jump start that memory back to life? Maybe even play with the contents of that memory?” asked Ramirez while giving a TEDx talk in Boston in June of 2013. So, that’s exactly what they did first—Ramirez and Liu found a way to target a single memory. In April of 2012, they published a paper in the journal, Nature describing their successful attempt to reactivate a fear memory in mice by using a new technology called optogenetic stimulation.

Optogenetics uses, as the name suggests, genetics and light to target and control the activity of specific cells under focus. In 2002, an opsin, or a light-sensitive membrane protein, by the name of channel rhodoposin (ChR2) was discovered. The gene of this opsin is installed into targeted neurons, which consequently express ChR2. Then, when blue visible light is applied to those cells, the protein channels open up creating a flux of ions resulting in activation. This gives the experimenters freedom to turn neurons “on” and “off ” with ChR2 essentially functioning like a switch in response to the presence of light. It provides scientists specificity, easy targeting, and less damage than using conventional electrical stimulation techniques.

Using this groundbreaking technique, ChR2 was packed into a genetically engineered virus and was injected into the hippocampus, the center for memory formation, of mice. More specifically, Ramirez and Liu were targeting a subpopulation of granule cells located in the dentate gyrus of the hippocampus where contextual aspects of memory can be traced. These cells are thus identified as contextual memory-engram cells. For the first five days, the mice were put in Box A to become habituated with light-stimulation and were on a doxycycline (Dox) diet. Dox was used to prevent the cells from being labeled with ChR2. So while in Box A, the cells that were encoding the contextual memory of A weren’t expressing ChR2. The mice were then taken off Dox for the next two days and were put in a different box, Box B, where they were fear-conditioned by receiving foot shocks. This time, the cells encoding the memory of the foot shock were now labeled with ChR2, making it easier to access and control those cells for testing. Mice were put back in Box A, to test for fear memory recall by shining blue light using an optic-fiber onto the labeled cells. When stimulated with light, the mice froze in Box A indicating Optogenetic stimulation Fear memory encoded ChR2- labelled mice are reactivated Mice freeze that the neurons that were active during fear memory encoding while in Box B were indeed reactivated.

But, during the summer of 2012, Ramirez and Liu delved further into a more manipulative task to answer their last question, “What if we reactivate a memory but tinker with it and possibly make into a false memory?” In this study, mice were once again injected with a virus carrying ChR2 into the dentate gyrus and were implanted with optic fibers. After recovering from the surgery, the mice were put in Box A and were off the Dox diet. They were allowed to encode the contextual memory of Box A and consequently these cells became labeled with ChR2. Following which they were put back on the Dox diet and were placed in a new environment called Box B. While in Box B, the mice received foot shocks (fear-conditioning) and the labeled cells from Box A, cells that were labeled with ChR2 while encoding the contextual memory of Box A, were reactivated by shining blue light through the optic fiber. Lastly, the mice were put back into Box A and observed the mice freezing in place expressing fear. 

What happened? Why did the mice become afraid of Box A when that wasn’t where they received the foot shock? When the ChR2 labeled cells from Box A were reactivated, the contextual memory of Box A became associated with the fear memory that was being encoded from the simultaneous foot shocks the mice were receiving. This led to the distortion of the contextual memory of Box A resulting in a new memory, a false memory. Subsequently, the mice froze when put back into Box A because they thought that was where they received the foot shock when in reality, this environment never posed a threat to them. This goes to show the vulnerability of memories and how easily modifiable they are. The implications of false memories are tremendous, having huge impact in many real-time situations such as when giving testimonials to the court.

In 1983, the McMartin Preschool, CA was charged with a sexual abuse case, prosecuting several McMartin family members and teachers of sexually abusing the children. The trial lasted seven years and cost $15 million making it the longest and most expensive criminal case in the US. In 1990, all the charges were dropped and no one ended up convicted. It was found that the abuse therapists interviewing the children fed them with suggestive information leading them to develop false memories of sexual abuse they never experienced. These videotaped interviews were crucial for the defense and influential in the jury’s refusal to convict. When asked about any advantages of memories being easily alterable, Dr. Germán Barrionuevo, a Neuroscience professor at the University of Pittsburgh, whose lab extensively studies the hippocampus, said, “The reconsolidation process of memories is useful when adapting to a new situation. ato fit the needs of the new environment.” Reconsolidation is a recently developed hypothesis on how memories are stored. Once memories are formed, they become labile and the engram (memory trace) can be reorganized through synaptic and system organization creating long-term memories and distributing them throughout the neo-cortex. However, when that consolidated memory is recalled, it once again becomes labile and can be modified. Once that memory is modified, it is then reconsolidated.

The reconsolidation hypothesis and the study’s findings may provide ways on how false memories can have clinical applications. Dr. Floh Thiels, a University of Pittsburgh associate professor of Neurobiology, said “We can use this to maybe treat PTSD for soldiers or people who have gone through a traumatic experience. It can also be used for memory-based anxiety disorders by pairing the activation pattern of those memories with something pleasurable to provide relief.” However this poses technical issues when trying to activate these memories of humans. Ramirez and Liu used optogenetic stimulation on mice but this technique hasn’t been tested on humans as of yet and will take a long time to get it approved for clinical use. But when it does, optogenetics with false memories can be an instrumental tool for treating psychiatric disorders or learning more about the brain circuitry and specifically to memory formation. “It’ll be interesting to see if the process of creating false memories recruits the same machinery that was used for creating the original memory,” said Dr. Thiels when asked about how she would take this research forward. Even without taking this research forward, however it will be a shame not to, this study provided the first direct experimental evidence that false memories can be created physiologically. The significance of the findings is extraordinary and, not to mention, could be a basis for another great Christopher Nolan movie.