Understanding how memory in the brain works remains one of the most difficult and insight-resistant issues in neuroscience. Also, like most things about the brain (human brains, any brains), the more we look, the more complex it becomes. The research by a team from Kansas and New York (USA) on prion-like proteins is a good example. They found that while prions (a form of protein that behaves like a virus) produce mis-folded proteins and fatal diseases such as mad-cow disease (BSE) in cattle and Creuzfeldt-Jacob Syndrome in humans, the folding of proteins in this way may be an important component of memory.

One of the characteristics of prions is their ability to ‘infect’ proteins, forcing them into a particular shape (conformation folding), which from then on becomes essentially permanent. These mis-folded proteins accumulate in the brain and eventually destroy brain function. However, researchers have also noticed that there are several normal proteins that have prion-like characteristics. One of these, a protein called CPEB (in case you wanted to know: Cytoplasmic Polyadenylation Element Binding), has the ability to force other proteins into an alternate conformation (shape change) and that conformation is heritable whenever that protein is reproduced by a cell. It is this persistence of the protein shape – after having been transformed by CPEB – that suggested to researchers that CPEB might play a role in the persistence of memory.

Of the many unknowns in brain memory function, one of the most intriguing is the question: How is it that given the instability of organic material, memories can be created that are persistent over a long term (in fact, decades)? In biology, when something needs to persist, it’s usually somehow incorporated into the cell reproduction cycle (mitosis), or for species reproduction (meiosis). Now memories do not persist from parent to offspring, but they might well persist in the memory cells of the brain through the reproduction cycle. If so, then something that ‘freezes’ the conformation (shape) of proteins, so that they reproduce in more or less the same way from generation to generation – that could be one of the key mechanisms of memory.

Kausik Si of Stowers Institute for Medical Research together with Nobelist Eric Kandel suggest in this research performed on the sea-slug Aplysia and published in the journal Cell, that CPEB is found at the brain cell sites where serotonin (a known memory stimulant) is administered. Moreover, other proteins at that same site are found to be in their folded, permanent conformation state, and clumped together as would be expected if a prion had affected them. This effect was prevented by administering an antibody (protein reactant) that blocked the protein clumping. As researcher Si put it:

“These results are consistent with the idea that ApCPEB [Ap=aplysia] can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time”. Si cautions, however, that they haven’t yet proven that blocking CPEB’s ability to self-perpetuate also blocks memory. For that, he says they would need to see whether a slug with a mutant version of the protein would learn but then quickly forget.

“Persistence of memory is a difficult problem,” Si said. The new evidence offers “at least an idea” for how this may happen and he suspects the prion-like protein’s apparent role in memory may turn out to be a more general phenomenon. His group is following up on their findings by investigating the role of the fly version of CPEB, and Si notes that humans do have a similar protein.

[Source: EurekAlert]

Yes, humans do have a similar CPEB protein, but this research is a long way from following the molecular chain from a sea-slug to the human memory. However, it does make a powerful suggestion: Memory is almost certainly going to be, at least in part, the function of a persistent cell-hereditable conformation of proteins. Looking at CPEB is a very good place to start.