We learn from our personal interactions with the world and memories of such experiences help guide our behavior. Experience and memory are inexorably connected, or at least they looked to be before a recent study reported the formation of completely artificial memories. In this pioneering study, investigators used laboratory animals to reverse engineer a specific natural memory by mapping the brain circuits underlying its formation. Then, they “trained” another animal by stimulating brain cells in the pattern similar to the natural memory. By doing so, they created an artificial memory that was retained and recalled in a manner that was identical to a natural one.
Memories are essential to upholding the identity that emerges from the narrative of personal experience. This extraordinary study demonstrates that by manipulating specific circuits in the brain, memories can be disconnected from that narrative and molded in the complete absence of real experience. Their work shows that brain circuits that typically respond to specific experiences can be artificially stimulated and can also be linked together in an artificial memory. Such memory can be produced by the appropriate sensory cues in the real environment. The research clearly provides a fundamental understanding of how memories are formed in the brain and are significant in a burgeoning science of memory manipulation that covers the transfer, prosthetic enhancement, and erasure of memory. These efforts could potentially have a tremendous impact on a wide range of individuals, ranging from those struggling with memory impairments to those suffering from traumatic memories. They can even have broad social and ethical implications.
The natural memory formed in this recent study was created by training mice to associate a specific odor of cherry blossoms with a foot shock and they learned to avoid by taking an alternative route in a rectangular test chamber to another end infused with a different odor of caraway. The researchers found that cherry blossom emitted by acetophenone activates a specific type of receptor on a discrete type of olfactory sensory nerve cell in the mice.
They then applied optogenetics, a sophisticated technique to activate these olfactory nerve cells. Optogenetics uses light-sensitive proteins to stimulate specific neurons in response to light brought to the brain through surgically implanted optic fibers. In their initial experiments, the researchers used transgenic animals that only produced the protein in acetophenone-sensitive olfactory nerves. After pairing the electrical foot shock with the optogenetic light stimulation of the acetophenone-sensitive olfactory nerves, the researchers taught the mice to associate the shock with the activity triggered by specific acetophenone-sensitive sensory nerves. When they later conducted trials, the mice avoided the cherry blossom odor.
These trials showed that the tested animals did not need to actually experience the odor to remember a connection between that smell and a harmful foot shock. But then again this was not a completely artificial memory as the shock was still quite real. To completely construct an entirely artificial memory, the scientists had to stimulate the brain in a manner that mimics the nerve activity caused by the foot shock as well.
Earlier studies have revealed that specific nerve pathways leading to the ventral tegmental area (VTA) were vital for the aversive nature of the foot shock. To generate a truly artificial memory, the researchers had to stimulate the VTA just like they stimulated the olfactory sensory nerves. But, these transgenic animals only produced the light-sensitive proteins in those nerves. To utilize optogenetic stimulation, the scientists stimulated the olfactory nerves in the same genetically engineered mice and used a virus to place light-sensitive proteins in the VTA. They triggered the olfactory receptors with light to simulate the odor related to cherry blossoms and then stimulated the VTA to mimic the aversive foot shock. The test mice recalled the artificial memory and responded to an odor they had never encountered by avoiding a shock they had never ever received.
For a long time, it has been a mystery how memories are formed in the brain—and what physical changes in the brain accompany their formation.
In this study, the electrical stimulation of specific brain regions that triggered a new memory also activated other brain regions known to be linked with memory formation, including the basolateral amygdala. As nerve cells communicate with one another through junctions termed synapses, it has been assumed that changes in synaptic activity cause the formation of memories. In other experiments, memories have been partially transferred in rodents with recordings of the electrical activity of a trained animal’s hippocampus i.e. memory center to stimulate similar patterns of nerve activity in a recipient animal. This process is similar to the one adopted by this study, in that stimulating the electrical activity of specific neural circuits is employed to elicit a memory. In the case of actual memory transfer, the pattern came from trained animals, whereas in the optogenetics trials, the pattern of electrical activity associated with the memory was built ‘de novo’ within the brain of the tested mouse. This report is the first-ever about a completely artificial memory, and it helps establish a fundamental understanding of how memories may be manipulated to some extent.
In recent years, research into memory and efforts to manipulate it have progressed at a rapid pace. A “memory prosthetic” was designed to enhance its formation and recall with the help of electrical stimulation of the memory center in the human brain with support from the Defense Advanced Research Projects Agency (DARPA). In contrast, a memory erasure using the so-called Eternal Sunshine drug (zeta inhibitory peptide or ZIP is being developed to treat recollections of chronic pain.
There are legitimate motives behind these efforts. Some people may try to recover lost or partially lost memories while others may seek relief from traumatic memories related to post-traumatic stress disorder or chronic pain, by trying to erase them.
The methods used in these trials to create artificial memories will not be employed in humans anytime soon as we are not transgenic like the test animals nor are, we likely to accept numerous implanted fiber-optic cables and viral injections. Yet, as technologies and strategies progress, the possibility of manipulating human memories will grow more realistic.
Creating artificial memories unravels the mystery of how memories form and could ultimately help us understand and treat diseases such as Alzheimer’s. At the same time, we need to be vigilant that any manipulations are approached ethically.