Doctor thinking about medical errors

We all have memories; some are pleasant, some less so, some have emotional content (my first date), some have none (I am not going to dip my hand in boiling water because I got scalded when I was young and didn’t listen to my mom). But did it ever occur to you that we really don’t know how we remember? Yes, I know, everybody knows that there is a special area in the brain called the hippocampus where memories reside. But that only tells us about the anatomical location of memories, not how they are made. A recent amazing experiment, using our distant cousin the fruit fly, took a first stab at this problem. The results of the Oxford University-led study are published in the journal Cell.

Scientists have used light to program the memories of fruit flies. Think about it: light to program memories! The research team genetically engineered the fruit flies so that a small set of nerve cells in the brains would “fire” in response to a flash of laser light. This showed which cells are involved in how a fruit fly learns and remembers what to avoid, and offers an exciting new opportunity to investigate how memories are formed.

Remote-controlling these cells and turning them on using light creates an illusion in the brain of the fly that it is experiencing something bad. The fly learns from the ‘mistake’ it never really made and improves its actions the next time,” explains Professor Gero Miesenböck of the Department of Physiology, Anatomy, and Genetics at Oxford University, who led the work.

The Oxford scientists, with colleagues at the University of Virginia, Charlottesville, demonstrated that they could use flashes of laser light to train flies to dislike a certain odor.

They tracked the flies using a video camera as they moved around a small chamber while two different odors were fed into the chamber from either end. They found that they could implant a lasting preference for one odor over the other by remotely activating a specific set of brain cells each time a fly strayed into a particular odor. Using this method, the researchers were able to pinpoint the precise nerve cells that are responsible for telling the flies that they’ve done wrong, narrowing down the search from the 100,000 cells in the brain of a fruit fly to a set of just 12 neurons.

This puts them in position to follow this up and start to characterize the process by which memories are formed and organized.

Surprisingly, the source of these signals is in a limited number of cells—just twelve. These cells send the signals that train the fly to associate the odor with something bad, so wherever their signals go must be the seat of memory. They can now follow this up and start to characterize the process by which memories are formed and organized.

While this work has been done in fruit flies, general lessons about how actions are learned and memories are stored should hold true for humans.

What is the relevance of fruit flies memories to our infinitely more complex brain? Biology teaches us that fundamental mechanisms tend to be conserved. Learning about the storage of memories from brain cells in flies should tell us a lot about how they are stored in humans. Professor Miesenböck has pioneered this method of genetic engineering to remote control the action of specific cells within tissues, or whole organisms like worms, fruit flies, fish, and mice, using light from the outside. These efforts have given rise to a new field sometimes called “optogenetics”, to indicate that sensitivity to light is encoded genetically.

As the ability to write memories directly to the brains of fruit flies demonstrates, optogenetic techniques have particular power in neuroscience. Why?

Because we are no longer just passive observers of processes in the brain. In the past, neuroscientists had to be content with recording the chatter of brain cells and trying to infer what it all meant. The ability to talk back and influence behavior directly is a game changer.

But do you get the vaguely discomforting feeling as I do, that such techniques in the wrong hands can be abused? After all, genetically engineering human beings is already in clinical trials as a way to treat certain diseases. Once we master the technique, what would prevent a rogue scientist or a malevolent government from using it to control thoughts and behavior by shining a laser light? Sounds like the stuff sci fi is made of. Am I becoming a paranoid conspiracy theorist? At the dawn of the molecular biology era, concerned scientists saw the potential for mischief in the misuse of DNA genetic engineering. They convened in Asilomar, a conference site in Northern California, and hammered out a code of scientific conduct that has served scientists and society exceedingly well. It is time for neuroscientists to do the same.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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