Making a Long-Term Memory? Don’t Forget to Tag it!

I’m sure you all know that you have both a short-term and a long-term memory. Many people think of those as separate things, and to us, it may seem that way. But in fact, the formation of short and long term memories in the brain is very intertwined, and a short-term memory can become a long-term one. What we don’t really know is HOW this happens. What makes the difference between remembering a phone number for a few minutes and remembering it for months? Turns out, it’s a simple tag.
ResearchBlogging.org Ballarini et al. “Behavioral tagging is a general mechanism of long-term memory formation.” PNAS, 2009.


Short term memory (STM) and long term memory (LTM) are actually not just different in terms of time, they are different in mechanism, in how they form. LTM relies on actual synaptic changes in the brain over a period of time, meaning that new proteins have to be synthesized, while right now we think that STM relies more on increases or decreases in firing rates of neurons, without permanent changes at the cellular level.

So if LTM formation means that synapses are changed, it’s going to require the synthesis of a lot of new proteins, specifically in the area of the hippocampus, a brain area closely associated with learning and memory. The hippocampus is a little curly bit near the bottom of your brain, inside the temporal lobes, and the word means “sea horse” in Greek, probably because it’s nice and curly.
hippocampus1.png
What the scientists in this experiment wanted to do was to test what triggers a STM (changes in firing rate), to become LTM (actual changes in synapses). We know that, for LTM to form, plasticity-related proteins have to be synthesized. But what triggers the synthesis of these proteins? The scientists found that there was a behavioral “tag” that would cause formation of new protein and formation of LTM. And they had a beautiful way of doing it.
Take a bunch of rats. Give them weak training in a behavioral task, which will induce short-term memory (about 30 minutes), but not LTM (it was gone the next day). This task is known as the spatial object recognition task. Give the rat two things, say a blue block and a red ball, and put them in different areas of the cage. The rat will explore the new toys, and because they are both new, it will spend about 50% of its time at each toy. Take out the toys.
30 minutes later, put them back. But THIS time, put one of them (say, the red ball) in a different place in the cage, while the blue block remains in the same condition. If the rat has STM, it will spend far more time exploring the red ball in the new location, because it remembers that the blue block was there before.

Because the rats are only trained once on this, they are only good for a little while. But, if you shake them up a bit, something different happens. If you put them in an open field (an open box that is different from their cage) for 5 minutes an hour before or an hour after exposure to the toys for the first time, the rats developed LTM for the position of the toys, lasting well into the next day. Why? Well, previous studies had shown that exposing rats to something new before training makes them more likely to form LTM, and more likely to have the changes in protein expression that go along with LTM (whether this is due to stress, vigilance, or simply being more awake, Sci isn’t sure, she’ll have to read up on that and get back to you).
So then, the scientists did something interesting. They took these rats and went to train them with LTM, but before they did, they infused a drug into the brain (anisomycin), which blocks the transation of RNA into new protein. Thus, the rats would be unable to produce new proteins during training. And when they were unable to produce new proteins, the rats could not form the LTM during the training task. They tried this with two separate hippocampus-dependent tasks (spatial object, conditioned freezing, and one task that is hippocampus-independant (conditioned taste aversion), and all of them had the same result. Translation of new protein is clearly required for the formation of LTM.
Thus, is appears that a novel environment before training is a behavioral “tag” that induces protein synthesis, causing memories formed either immediately after or immediately before to become LTMs. A behavioral “tag” induces physical changes in the brain. And it turns out that this is not just hippocampus-dependant. The authors got similar results when they inactivated the hippocampus during training, meaning that the cortex or other areas may also be involved.
What I like about this study is that it’s a study done entirely in a behavioral model, with infusions to changes specific brain areas affecting the behavior. That way, it narrows the development of the behavior down to specific brain region in the rat (and presumably, in the human), showing a really nice link between protein synthesis in the hippocampus and cortex and development of LTM.
But what does this mean? It means that, if you want to store something in your LTM (anybody got a test coming up?), it might help to associate your learning it with something novel. Of course, you can’t go out and ride a roller coaster for each new fact, but sometimes writing a haiku or something silly about what you’re learning could be novel enough to help form that memory.

Forming LTM?
attempt some poetry for
behavioral tags.
Or perhaps…
There once was a sad undergrad
and her memory, oh it was BAD!
But she read this science note
and science poetry she wrote
and her orgo chem grades now are rad!
Ballarini, F., Moncada, D., Martinez, M., Alen, N., & Viola, H. (2009). Behavioral tagging is a general mechanism of long-term memory formation Proceedings of the National Academy of Sciences, 106 (34), 14599-14604 DOI: 10.1073/pnas.0907078106

9 Responses

  1. Very interesting to a lay person. It makes me wonder if the reason that I remember even trivial moments of LSD experiences ten years later is because the drug made everything appear strongly novel?
    It always had the sensation of two weeks travel in a foreign country compressed into eight hours.
    Sorry for introducing the whack job acid-freak element, it just struck me very strongly when reading this.

  2. Very interesting. I’m just wondering: how long can something be held in STM? I thought that it was more within the range of seconds than minutes (and that everything else is some form of LTM), but either I’m wrong (entirely possible), or this article is using some other definition of STM than I think I was taught. The reason I’m asking is that I’m kind of surprised that putting the rats in the open field an hour after the task also helped to form LTMs. Intuitively it seems to me that the memory would have faded from STM a long time before the open field.
    Also, when learning something, isn’t that something always more or less new/novel? If it wasn’t, then you wouldn’t need to learn, right?
    Lastly, is it also possible to develop drugs that would aid the rats in the production of the required proteins so that everything in STM is automatically converted to LTM when they receive the drug (or something like that)?

  3. Allan, I can remember such LSD moments from 45 years ago. You may be on to something. However, I wonder if our brains are simply wired to remember things that are accompanied by a state of emotional arousal. I have vivid recall of many emotional events from my past that did not occur in novel or unfamiliar environments. Is it possibly the emotional arousal of an unfamiliar (new) environment that enhances LTM formation and possibly enhances other mental processes as well. I know that my brain is most creative and I’ve had some of my best ideas when I’m on a long road trip. Everything in my field of awareness is constantly changing. LSD is certainly one of the most emotional experiences I have ever had.

  4. I wonder if LSD (and similar psychedelics) somehow disconnects the facility that identifies well-known stimuli as “not-novel”? This would explain the sense of “lots going on” often experienced in trips, along (perhaps) with the sense of “general interconnectedness”. (OTOH, the latter might be a result of over-stimulation, or under-repression, of one of the associative facilities that normally recognize connections via “chained associations”.)

    [I]s it also possible to develop drugs that would aid the rats in the production of the required proteins so that everything in STM is automatically converted to LTM when they receive the drug (or something like that)?

    I see two potential problems with this.
    First, drugs tend to have a “shotgun” effect with a very broad muzzle blast (metaphoric connotations on purpose). I doubt that you could find a drug to stimulate this process that doesn’t also stimulate many others, perhaps unwanted, perhaps undiscovered until a generation of students had been using it.
    Second, I seriously doubt that you would want everything in STM to go into LTM. Especially stuff you do every day; do you want to remember every breakfast you ever ate?
    IMO a better approach would be to go looking for some novel stimulus when you’ve laid down STM you want to remember. The Web might be a good place, or perhaps 1PS games that generate novel circumstances each time you play.
    Which brings up an interesting question: could somebody (or somerat) become habituated to novel situations such that their overall level of STM>LTM conversion became reduced? Adding in another likely source of conversion, I wonder if a combination of novelty and life-threatening circumstances (i.e. combat) could result in long-term changes to how the STM>LTM conversion works.

  5. In response to Jordi, yes, information in STM as defined by anyone I’ve ever read, only lasts a few seconds unless the info is rehearsed. That’s why we repeat a phone number over and over until we can write it down.
    The whole novelty thing does work for remembering info, but even better is finding ways to make the information meaningful to you and your knowledge set. That gets it connected to your network of knowledge. Two ways to better remember information, like when you’re studying, are to organize it in a way that’s meaningful for you and to elaborate on it by adding your own details.

  6. Short Term Memory is a term used differently by folks who study memory at the neuronal level and folks who study it at the behavioral (and sometimes the neuroimaging) level in humans. Actually, it looks like there may be several slightly different terms and not all of them have been reconciled within or between the fields. In cognitive science people talk about STM, WM, LTM, but also several variants, and sometimes these are tied to neural activity sometimes not.

  7. I doubt there’s any real dividing line in memory timings, at least until you get to the point of laying down long-term memories.
    The shortest-term “memories” would probably be actual firing loops (feedback, etc.) within or between cortical regions (and nuclei such as the thalamus, hippocampus, etc.) Next would be short term potentiation and depression, including desensitization. Let me blockquote from “From Molecules to Networks, Second Edition: An Introduction to Cellular and Molecular Neuroscience” edited by John H. Byrne and James L. Roberts:

    Desensitization is a very important process whereby cells can decrease their sensitivity to a particular stimulus to prevent saturation of the system. Desensitization involves a complex series of events ([refs]). For GPCRs ([G-Protein Coupled Receptors], desensitization is defined as an increase in the concentration of agonist required to produce half-maximal stimulation of, for example, adenylyl cyclase. In practical terms, desensitization of receptors produces less response for a constant amount of transmitter.

    There are two known mechanisms for desensitization. One mechanism is a decrease in response brought about by the covalent modifications produced by receptor phosphorylation and is quite rapid (seconds to minutes). The other mechanism is the physical removal of receptors from the plasma membrane (likely through a mechanism of receptor-mediated endocytosis) and tends to require greater periods (minutes to hours). The latter process can be either reversible (sequestration) or irreversible (down-regulation).

    (The link is to the first edition, but the quote is typed in from the second. I would have provided links to Wiki, but it would have gotten the comment shuffled to the moderation queue and put Sci to the trouble of freeing it up. Still, most of the technical terms are easily found there.)
    This process, along with others such as the short-term, temporary response to calcium brought into the cell by NDMA receptors, probably provides a seamless bridge between the sub-second firing loops of “traditional” STM and the hours-later processes that incorporate such memories into LTM.
    I should mention that the book I blockquoted is a pretty awesome text for those deep in the subject. While I couldn’t recommend it for those not interested in the technical details, I can strongly do so for anybody so interested. I’ve been reading it, and will probably do a (highly favorable) review in a week or so.

  8. Sounds beautifully simple, but “memory tagging” can be a lot harder than it sounds – especially if there’s some sort of injury other physiological imbalance. I now have to constantly “memory tag” after suffering traumatic brain injury in a bad car/bike accident 10 years ago. I’m much better now, but for about a month I had no short-term memory (like Memento or the 10-second guy in 50 First Dates). I remembered everything I learned up until the accident – even organic chemistry equations that I vowed to forget to they don’t take up RAM – but I couldn’t remember something I learned less than a minute before. In rehab they had me write things down in a “memory log” so I could refer to it if I had any questions (like “Um, why am I in the hospital?”). It took years to get back to “normal” – and after 10 years it looks like I’ll never regain my former aptitude – but I can certainly attest to neural plasticity (and bike helmets)!

  9. RE: LSD
    Norepinephrine is released by locus coeruleus neurons in response to salient stimuli (including novelty). The locus coeruleus projects to the hippocampus, where it promotes long-term potentiation (presumed neural correlate of memory traces).
    http://www.ncbi.nlm.nih.gov/pubmed/17765726
    Interestingly, LSD and mescaline suppress spontaneous activity of the locus coeruleus in anesthetized animals. They also increase the response of the locus coeruleus to noxious stimulation of the sciatic nerve and cause its cells to burst in response to innocuous stimuli such as stroking the fur on the animal’s back.
    http://www.ncbi.nlm.nih.gov/pubmed/7357465
    The 5-HT2A receptor, the main site of action of psychedelics, promotes memory in eyeblink conditioning in rabbits, and polymorphisms in the gene for this receptor have been associated with episodic memory in humans.
    http://www.ncbi.nlm.nih.gov/pubmed/14557608
    http://www.ncbi.nlm.nih.gov/pubmed/18602445

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