Wednesday, April 8, 2009

The Incredible Erasable Mind

The idea of erasing one's memory has been around for a while. It plays a prominent role in science fiction literature and movies, like Men in Black and The Eternal Sunshine of the Spotless Mind. And until now, it has remained in the fictional realm. Recently, however, a team of scientists at the Department of Psychology and Gene Research Center in Brooklyn, New York discovered that the fiction that we read and watch is getting closer and closer to the truth.

What They Knew
The team of scientists - including those that were quoted in the NY Times article, Todd Sacktor and Andre Fenton - set out to determine several things, using previously gathered information. Firstly, they knew about the existence of protein kinase C (PKMzeta). PKMzeta is an autonomously active protein enzyme that is known to store unpleasant memories. This enzyme was discovered when a PKMzeta-inhibitor was injected in to a rat's brain, and the rat promptly forgot it's "unpleasant" memory.

How PKMzeta Works:
PKMzeta is necessary for the continuation of induced long-term potentiation in synaptic transmission. We already know how a synaptic transmission works. Long term potentiation is a state of increased sensitivity that's triggered when a synapse is stimulated. PKMzetas interfere by gathering themselves in to the receiving end of a synapse, which further increases sensitivity. 

The scientists used two PKMzeta-Inhibitors for the experiment: zeta inhibitory peptide (ZIP) and Chelerythrine.  Chelerythrine and ZIP are cell-permeable PKMzeta-inhibitors. They reverse synaptic potentiation in the hippocampus when applied up to 1 day after long term potentiation is induced, essentially stopping the long term potentiation.

What They're Asking
The scientists were curious about how selective PKMzeta was when storing memories. Were all forms of memory and information in the brain stored by PKMzeta?

The Experiment
Equipped with Chelerythrine, ZIP, a harmless saline solution, several rats, and platform at which one end a shock was received by the rats, they were ready to see how important PKMzeta was when it came to "place avoidance memory", or "spacial memory". 
On the first trial, rats ran to the shock zone within 2 seconds, but after a while, they learned to avoid it. Twenty-two hours later, Chelerythrine was injected in to the dorsal hippocampus of some rats, saline solution in to others, and their retention of the avoidance memory was tested 2 hours after the injection.  

The Result
The graph shows that the naive rats entered the shock zone rapidly, but had learned to avoid the location for several minutes by the 8th training trial. As soon as Chelerythrine was injected into the dorsal hippocampi, the retention of the place avoidance memory was essentially erased, causing avoidance of the shock zone to drop to the level of a naive rat. During the long term memory retention trial it was discovered that the rats still showed no signs of recognizing the shock zone. However, after a single training trial, they began to avoid the shock zone. The same trial was performed using ZIP, with almost identical results. 

This told the scientists that ZIP and Chelerythrine are interchangeable PKMzeta-inhibitors. They also learned that neither PKMzeta-inhibitor permanently disabled the rat's ability to store memories. Finally, they successfully determined that PKMzeta is directly involved in spatial memory.

The scientists conducted other experiments, testing the relationship between PKM-zeta and Classically Conditioned Fear Memory using shock tests and Instrumentally Conditioned Memory using a dark compartment. Having determined the similarity between Chelerythrine and ZIP, they continued their experiments using only ZIP, this time injecting it in to either the basolateral amygdala or the dorsal hippocampus. Through all their tests, they found that specific inhibition of PKMzeta impaired the retention of accurate associations in different brain regions, regardless of positive or negative reinforcement, essentially erasing specific memories. This revealed to them that PKMzeta is a general molecular mechanism for memory. They also determined that the PKMzeta-inhibitors that they used erased the memories without disrupting the function of the region in which it was injected. 

The Ethics Question
The team of scientists say that they are fairly confident that the PKMzeta-inhibitors will translate well from rats to humans. If we had the ability to successfully erase specific memories in a human being, how would we use it? Is it worth having in order to erase the memory of a traumatic event, even if it might end up in the wrong hands? The debate rages on, and I don't think there will ever be an end to it.

1. PKMzeta Maintains Spatial, Instrumental, and Classically Conditioned Long-Term Memories, research article, PloS Biology, Dec. 23, 2008
2. Brain Researchers Open Door to Editing Memory, NY Times, April 6, 2009, Benedict Carey

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