Forget everything you know about memory

The exam is sitting in front of you, mocking you. The blank spaces under the questions are cavernous, the scantron bubbles are – unlike your understanding – crystal clear, and when you look at your Casio, all the screen displays is “666” because you can’t remember a damned thing. But why not? Isn’t memory just like a computer’s desktop? Files stored neatly, right where you put them when you listened in lecture? This is a common misconception of memory.

As with many other common ideas of complex functions, the impression of memory is largely flawed.

Researchers like Terje Lømo, Gary Lynch and most recently Dr. Todd Sacktor, professor of physiology, pharmacology and neurology at the State University of New York, are unveiling what actually makes our memories along with how they stick and how to strengthen, and erase, everything you’ve ever stored in your mind.

Reconsolidation

Many people imagine memory to be a storage space, almost like a file cabinet, where you can go, look at whatever you need at that particular time, and then put it back in its place and leave it as it always was. We’ll call this File Memory. Not to say this doesn’t happen sometimes, but File Memory isn’t a complete explanation of how we remember.

Reconsolidation, a distinct process that maintains, modifies or consolidates memories, was first observed as early as 1968, and in recent years is beginning to be more complexly understood.

During reconsolidation, memories are actually moved out of long-term memory while you’re using it, thinking about it, or talking about it. They are then resaved again.

To liken it to the file cabinet analogy: when the memory is recalled, the file cabinet is destroyed, and the file is sent up for use, so you can alter it, strengthen it, and update it before it goes back. Then, when the memory is stored again, another file cabinet is built to hold it. But, this file cabinet may not be made the exact same way. It could be stronger, more complex, larger, and will be somewhat a little different than the last one.

Todd Sacktor, professor at the State University of New York, says of reconsolidation, “the whole idea of reconsolidation is that it both strengthens old memories – because it gets used again – and it updates the memories with new information.”

That’s why reading your notes the same day you took them can be so useful: you have an initial memory – you remember taking the notes and in what context they were taken - that you take out, build on, and reinforce before storing it again, this time more complexly and permanently.

Protein kinase M zeta (PKMzeta)

Even though the “File Memory” concept is largely inaccurate, we can find some similarities human memory has to that of a computer’s. In a computer, memory is stored through combinations of 0s and 1s. Though the information it stores is complex, it is constructed by those two basic blocks. This can also be compared to human genetics: DNA codes our entire genetic structure while itself being made up by four distinct chemicals.

Memory too, for all its complexity, is stored by one very basic building block: protein kinase M zeta, also known as PKMzeta. PKMzeta is what builds and keeps all types of memories in long-term storage, all over the brain.

With the presence of more of the enzyme, the result is stronger memories. This being said, conversely less of this enzyme means weaker, or no, memories.

The most well-known and illustrative proof of this resulted from a study by Sacktor, in partnership with the Israel Weizmann Institute of Science. The experiment consisted of having rats associate the action of intaking sugar water with discomfort, and then breaking them into three groups: one where PKMzeta was inhibited, one where PKMzeta was made to overexpress, and one control group.

A drug called zeta inhibitory peptide – ZIP – was administered to wipe the rats’ memory in the first group. ZIP does not even require the memory to be in the process of reconsolidation for it to work. Dr. Sacktor says of this “inhibiting PKMζ is like dissembling all one’s file cabinets, regardless of whether they are opened or not. After the drug has worn off, the pieces do not reassemble.” This was definitely observed in the experiment, and the rats were no longer wary of the sugar water.

In the group where PKMzeta was made to overexpress itself, the rats were even more afraid of the sugar-water than the control group. This phenomenon surprised Dr. Sacktor: “If you had a computer hard-disk and the 1 is the PKMzeta and the absence of PKMzeta is the 0, and then you randomly throw in a whole bunch of 1s into the hard-disk,” which is effectively what adding PKMzeta would do, “you’re going to degrade the information, just as you would by throwing in a whole bunch of 0s. But somehow if you throw some in – not a huge amount of 1s – there’s some aspect of the memory in which the 1s tend to go where the other 1s are, and then that makes the memory stronger. But it’s still pretty mysterious.”

Applications

As with most major scientific developments, the ability to wield the newfound knowledge often emerges much later, after the discovery.

“Once you understand the storage of information - even though it may take a couple of decades for that to change things – everything gets changed,” says Dr. Sacktor. “For example, when they figured out in 1955 the structure of DNA and convinced everyone that that was the genetic information, you could ask the same question ‘what difference does it make that we know that DNA is why some people’s eyes are blue and some people’s eyes are brown? We kind of knew that from Mendelian genetics anyway!’ It took decades before it actually made much of a difference for medicine.

I can’t predict what the real implications [of PKMzeta] are going to be. But it’s going to be something big.”

Already there is recognition of how many major applications this discovery could yield. Mild reconsolidation blockades have already been tested on subjects suffering from Post Traumatic Stress Disorder, results showing promise for the future of this technology.

Other applications could include helping addicts successfully kick their habit, healing some pain caused by central neuropathic pain syndrome (pain that is still felt, even after physical healing) and perhaps slow or stop the progress of degenerative diseases like dementia and Alzheimer’s.

It is clear that this development will lead us in the future of understanding and manipulating memory.

Dr. Sacktor puts it plainly when he says “I suspect the 2000s - this 10-15 year period - are going to be a golden age for understanding long-term memory.”

We won’t soon forget this groundbreaking discovery.