Memory: Your Most Mysterious Friend

The Tonegawa Lab, MIT
The Tonegawa Lab, MIT
The Tonegawa Lab, MIT

Credit: The Tonegawa Lab, MIT

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Throughout the history of mankind, human beings have been fascinated by memory—how do we form, store, and remember memories? How do we lose them? As Aldus Huxley said: “Every man’s memory is his private literature.” Bob Dylan warned: “Take care of all your memories, for you cannot relive them.”

The idea that memory is stored in the brain as “persistent physical changes” goes back at least to Plato, but modern formulation of this hypothesis had to wait until the turn of the 20th century, when Richard Semon coined the word “engram” for these persistent changes. We have now identified a population of brain cells that hold specific memory. Not only that, we can now engineer these cells so that an animal’s memories, thoughts, and emotions can be manipulated—Ideas that have existed only in the realm of science fiction, until just several years ago. The hypothesis has been that when you encounter an episode a small population of cells deep inside your brain called the hippocampus fires. This is followed by persistent physical changes in these cells. You will recall this memory only when external stimuli re-activate these engram cells. These hypotheses have now been proven to be correct by using a technology called optogenetics. The key molecule for optogenetics is a light-sensitive protein called channelrhodopsin, extracted from green algae. A scientist can insert channelrhodopsin into memory engram cells. Subsequently, a scientist can activate these cells with blue light delivered through an optic fiber. This results in retrieval of the specific memory without relying on natural recall cues.

We usually rely on our memory to make numerous decisions in day-to-day life. However, it is well known in psychology that we make an incredible insistence on the basis of a false memory. When DNA tests were introduced into legal scenes, it was discovered that an alarming proportion of people had been imprisoned on the basis of false testimony. Apparently, under certain conditions, ordinary people mix up memory with imagination. We can now artificially implant a false memory in the brain of experimental lab animals. We hope such experiments will help scientists to find out the condition under which a false memory is formed in humans.

We can also engineer memory engram cells to cure depression and early stage Alzheimer’s, at least with laboratory animal models.

So, optogenetics has now demonstrated proof of concept for therapies. Can we translate these discoveries into medicine?

 

SUSUMU TONEGAWA
Neuroscientist, Nobel Laureate
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