Molecular Basis of Memory

Harvard biologists have identified a protein, called Armitage, which regulates the formation of long-term memories. By manipulating this protein, the researchers were able to both enhance and impair long-term memory formation in fruit flies, as measured by a classical conditioning paradigm using smells and electric shock.

Armitage - and other proteins comprising the RISC pathway - is also present in both mice and humans. It appears to play a regulatory role in memory formation such that destruction of the molecule is necessary for additional protein synthesis at the synapse, which ultimately results in behavior consistent with long-term memory formation.

While it is possible that this could lead to drugs that would enhance human memory, there are several complicating factors. First, Armitage is localized to the synapse, and so no one knows what its effects might be in other regions of the body and brain.

Second, what are the natural conditions that trigger the destruction of Armitage so as to consolidate a given memory? In other words, what "chooses" to remember? The authors propose that "an integrated sensory trigger" induces Armitage destruction, and that it "is triggered with neuronal specificity in order to produce memory-specific patterns of protein synthesis," but these are just descriptions, not mechanistic explanations of how this process occurs. We may indeed increase memory by interfering with this pathway, yet possibly with disastrous effects on memory selectivity: what would it be like to experience life without forgetting anything?

Jorge Luis Borges wrote about such a character, named Funes, who "remembered the shapes of the clouds in the south at dawn on the 30th of April of 1882, and he could compare them in his recollection with the marbled grain in the design of a leather bound book which he had seen only once, and with the lines in the spray which an oar raised in the Rio Negro on the eve of battle of the Quebracho ... These recollections were not simple; each visual image was linked to muscular sensations, thermal sensations. ... He told me, 'I have more memories in myself than all men have had since the world was a world..."

A related third point is that the study was limited to the olfactory bulb. Given that protein expression is stimulus-specific, the pathways involved in the formation of other kinds of memories could be different. The "neuronal specificity" and "sensory triggers" that cause formation of long term memories from specific experiences could also be drastically different depending on the type of stimulus.

Nonetheless, this is an interesting advancement in memory proteomics precisely because it allows us to ask questions about how memory selectivity is accomplished. This question is also of increasing interest to cognitive neuroscientists, given that "selection efficiency" appears to be one of the most important factors in individual differences working memory capacity.