October 28, 2008

Unlearning Memories: You Have Been Erased!

In the movie 'Eraser', John Kruger, played by Arnold Schwarzenegger, removed the identities and all relevant information of persons-at-risk and gave them brand new identities, to save their lives. The title of this topic derives its name from the famous dialog: "You have been erased!”.

In reality, memories can be erased too, even long term ones! In humans, diseases like Alzheimer’s dementia, cause defects in short term memory limiting further memory acquisition; which finally progresses to erasure of previously stored memories. In experimental animals, long term memories can be prevented if they are subjected to electrical shock, anesthetics (possibly work by disrupting London forces operating in hydrophobic pockets in dendrites thereby causing 'unbinding' of memory elements), hypothermia and other insults within 5 minutes of learning a specific task.

There are guardians of memories keeping a constant vigil so that ‘memories are forever’. For example, we have seen masons at work standing on those makeshift scaffolds. In our bodies too, a protein called PKM zeta constantly ferries across the synapse, to give its healing touch. A protein called PSD-95, when phosphorylated, takes the role of the scaffold, in this analogy. Inhibitors of PKM zeta cause loss of memory, as demonstrated in rats, when their memories for tastes vanished after a single ‘shot’ in their taste cortex. So, LTP is not the only mechanism that fosters memory and neural plasticity. Long term memory also uses gene activation and expression, and protein synthesis. Any interruption in either of these mechanisms will have its own deleterious effect.

Genes have been identified which produce proteins that are necessary for memory formation and their maintenance. These genes act fast in the central nervous system and are known as IEGs (Immediate Early Genes). IEG Arc, one such gene codes for Arc protein, which is abundant in the hippocampal neurons. Obviously, the mRNA (messengerRNA can be thought of as ‘command’ from a gene, while proteins are like the results of this command) for that gene is formed in the nucleus by transcription, but once transcribed, it goes to the dendritic spines (especially those which are active) along the cytoskeletal rail road formed by microtubules. In the dendritic spines they (mRNA) translate themselves into proteins, Arc proteins, in this example.

Guzowski et al did an interesting experiment. They infused antisense oligodeoxynucleotide (for the inhibition of Arc protein synthesis) straight into the hippocampus of rats. Antisense oligodeoxynucleotides (antisense ODN) are short sequences of deoxynucleic acids which block the translation of mRNA into protein. The rats forgot the tasks they learned, while they could still form new memories. Their spatial memory was badly damaged. They concluded that antisense oligodeoxynucleotides interfered with the maintenance phase of LTP.

rat negotiating Morris water mazeRats can be challenged spatially using the Morris water maze. As we see in the picture, the water pool has two raised platforms, which rats can locate (and remember) spatially after some training. Even the rats already trained successfully, lost this spatial (co-ordinates in space) memory and had severe difficulty floating, when they were challenged with these chemicals. Looks like, You Have Been Erased!

Contradictory (against the motion) Link: Memories like diamonds may be forver

ResearchBlogging.orgC. K. McIntyre (2005). Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus Proceedings of the National Academy of Sciences, 102 (30), 10718-10723 DOI: 10.1073/pnas.0504436102
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