Imagine having a memory that haunts you, sneaks into your daily thoughts and turns over on itself in your dreams. Escape seems impossible. Now imagine you are injected with a virus that blocks the expression of a certain protein known to reactivate memories. With minimal side effects and the small chance of erasing or altering other memories, would you do it?

Molecular memory modification (MMM) works by disrupting the neural substrates that preserve long-term memory, rendering them malleable once more at the reconsolidation stage of the memory model. Although only tested in animals, the intervention has shown to enhance, alter and erase memories. One theory for long-term memory retention is the influx of calcium that leads to the production of a brain-specific persistent isoform of protein kinase C, protein kinase Mζ (PKMζ). This enzyme is thought to phosphorylate downstream activators that maintain memory beyond the initial triggered event. In other words, PKMζ continually cements your life events together.

Pharmacological interventions show that inhibiting PKMζ disrupts memory retention, thus the aim of MMM is determining if overexpression of this enzyme will cause memory enhancement. The experiment involved conditioning rats to associate a sweet taste with an unpleasant stimulus. The memory of the newly formed association is tested days later by the rat’s aversion to the saccharine taste. The rat brains were bathed in a viral vector expressing PKMζ either before the training or before the memory test. In both cases the memory of rats treated with the PKMζ was significantly better compared to the control viral vector.

What happens to the brain architecture when flooding the brain with this drug? MMM could create too many recall receptors, which could lead to network-level imbalances by eliminating meaningful differences between neurons. It would be like trying to find a well-traveled path after a large snowfall: complete disorientation. So, safety is a large concern when relaying this technology in humans. While inhibitionThe process by which a presynaptic neuron makes the postsyna... could potentially be useful in disorders such as post-traumatic stress disorder, enhancement could improve memory for those with amnesia or in cognitive decline.

However, disturbing ethical conundrums arise. Individuals with altered memories will fundamentally believe new memories are real. The past creates our sense of self and directs our behavior, dictating our future emotional reaction to stimuli. Could interfering with memory change self-perception? Enhancing or diminishing memories could alter self-narrative and, in turn, identity. Still, it could be argued that identity is made up of beliefs, intentions and preferences and – due to its multiple facets – the individual’s identity is preserved.

One last point to remember: memory is determined by emotional weight. Altering a memory might unbalance the scale, changing what a person deems important enough to remember. However, since MMM only functions with the individual’s permission, it will only affect memories already consciously selected thereby leaving identity unscathed. It might even be suggested that the individual is promoting rather than threatening personal identity.

Is it possible to exert any control over remembering? Studies suggest yes. A level of memory suppression is possible by activating the prefrontal cortex, which downregulates the hippocampal regions, thus inhibiting memory formation. Further, anxious individuals over-recruit the amygdala in response to threat, which further suppresses remembering. Indeed, researchers found individuals with high anxiety have difficulty exerting cognitive control over memories with a negative valence. In other words, it’s harder to manipulate memories that make us uncomfortable precisely due to safety locks.

While MMM poses a powerful tool for altering specific long-term memories, this research is in its early stages. Disentangling specific memories will pose a major challenge, while using this technology in a morally justifiable way will add yet another level of complexity.

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Written by Teodora Stoica.

Images by Jooyeun Lee.

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References:

Hui K. (2014). The ethics of molecular memory modification, Journal of Medical Ethics, DOI: http://dx.doi.org/10.1136/medethics-2013-101891

Anderson M.C. (2014). Neural mechanisms of motivated forgetting, Trends in Cognitive Sciences, 18 (6) 279-292. DOI: http://dx.doi.org/10.1016/j.tics.2014.03.002

Marzi T. & Stefania Righi (2014). Emotions shape memory suppression in trait anxiety, Frontiers in Psychology, 4 DOI: http://dx.doi.org/10.3389/fpsyg.2013.01001

Wu-Zhang A.X., S. Nabavi, R. Malinow & A. C. Newton (2012). Cellular Pharmacology of Protein Kinase Mζ (PKMζ) Contrasts with Its in Vitro Profile: IMPLICATIONS FOR PKMζ AS A MEDIATOR OF MEMORY, Journal of Biological Chemistry, 287 (16) 12879-12885. DOI: http://dx.doi.org/10.1074/jbc.m112.357244

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