Going, going, gone: the where and why of memory erasure

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erase-memory

If you could erase your memories, which ones would you choose?

As a neuroscientist, one of my raisons d’etre is to achieve, in a way, some form of memory erasure, especially for individuals that suffer post-traumatic stress disorder, social anxiety or drug addiction. Each of these situations involves some form of persistent memory that interferes with everyday function.

So what can be done? The most obvious solution is to isolate the brain area that is storing the particular memory, and destroy it using electricity or chemicals. This is exactly how Michael Fanselow and his colleagues showed in 2007 that the amygdala is a likely candidate for the storage site of fear memories.

In Fanselow’s experiment, when rats were trained to fear a tone, they showed fear to the tone even 16 months after the training episode. Chemical lesioning of the amygdala, however, abolished any fear expression to that tone, erasing the fear memory.

Decay is the way

Another option is to accelerate the process of memory decay. According to the trace decay theory of forgetting, memories fade without rehearsals. Consistent with this idea, the neuroscientist Yadin Dudai hypothesised in 2007 that storage of a taste memory requires rehearsal in the form of ongoing chemical (namely, protein kinase M zeta – PKMζ) activity in the brain.

Without this activity, memories may slowly disappear beyond recovery. He attempted to accelerate this process in rats by a single injection of the PKMζ inhibitor “ZIP” in the insular cortex, an area of the brain believed to be responsible for our gustatory (taste) memories.

These rats showed an immediate deficit in recalling a taste memory, whereas rats that did not receive ZIP displayed eventual but significantly slower rate of forgetting. Such acceleration of forgetting was claimed to be erasure in this study because the memory couldn’t be recovered in subsequent tests.

Attempting memory erasure via acceleration of forgetting is a familiar concept to most us. In a previous article on forgetting, I mentioned how my colleagues and I had identified a neurotransmitter called gamma-amino butyric acid (GABA) that is at least partly responsible for forgetting.

Alcohol greatly increases GABA activity, hence it is possible that it accelerates forgetting and even causes erasure. We can assume James Bond’s alcoholism is aimed at erasing memories of a traumatic childhood event …

Pavlov’s dog

For those who want memory erasure but would rather not infuse chemicals into the brain or turn to alcoholism, there may be a cognitive-behavioural solution.

Famously, Russian physiologist Ian Pavlov, through an initial interest in the digestive system, noticed over time that his dogs salivated not to the food but to the bell that signaled food delivery minutes earlier.

He coined this reaction “conditioned reflexes”, and the process of pairing an initially neutral cue (the bell) with a biologically significant stimulus (the food) is now referred to as “Pavlovian” or “classical” conditioning. Significantly, Pavlov also observed that when he rang the bell repeatedly without any food, the dog’s salivation response to the bell disappeared.

He referred to such reduction in responding as “extinction”, and eventually won the Nobel Prize for his lifetime of work on associative learning.

Extinction is a very important concept because it forms the basis of cue exposure therapy for treatments of anxiety and addiction in humans. For instance, someone hit by a truck might show extreme nervousness on hearing any loud noise that resembles car honking; a therapist would then present loud noises in a safe setting until that person learns a loud noise does not mean collision with a truck is imminent, and is not afraid to go outside where there are loud noises everywhere.

Extinction

Unfortunately, it was later comprehensively shown that extinction does not cause erasure – rather it is a new learning that opposes the original learning. In animals and humans, changing the environment from the one in which extinction occurred was shown to bring back the original fear or addiction behaviour. This explains why an addict can do well in a rehab but relapse as soon as he/she is returned to the real world.

But there is still hope. My colleagues and I showed that when extinction is performed in juvenile rats, changing the environment or giving reminder fear cues does not bring back the fear. Fear is gone, in other words, for good: extinction is erasure in juvenile rats.

We are not saying that the juvenile rat is not even remembering the previous fearful experience – it may well be thinking: “hmm … yes this bad thing happened two days ago …” But the physiological reactions indicative of fear are absent in these animals due to extinction.

Further studies showed that extinction in adult rats relies on an array of chemicals in a variety of brain regions but extinction in juvenile rats do not. Extinction early in life only seems to require opioid activity.

We are now trying to understand better why extinction, a purely non-invasive behavioural treatment, causes erasure early in life. We would like to figure this out so we can reproduce such erasure in adult animals. Then maybe we can also erase some terrible and powerful emotions some people feel.

Maybe one day you will be able to erase memories of an ex-lover like Joel and Clementine in the movie Eternal Sunshine of the Spotless Mind. Dr Sheldon Cooper from the Big Bang Theory also may finally wipe his memory of Ben Affleck as Daredevil.

I would like to erase my own memories of the past wrongdoings so I can feel better about myself. But it will probably make me a worse person. Whether memory erasure is ethical or not is outside my scope.

Interestingly, a study published in Science last year showed that opioid injected into the spine, not the brain, erased memory trace of previous electrical stimulation present in the spine.

This made me think that perhaps to achieve memory erasure we need to go beyond the brain.

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One comment

Hotel Luang Prabang #permalink

Great article, I really enjoyed reading it!

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