reconsolidation

A Trace of Memory: Researchers Watch Neurons in the Brain During Learning and Memory Recall

A team of neurobiologists led by Simon Rumpel at the Research Institute of Molecular Pathology (IMP) in Vienna succeeded in tracking single neurons in the brain of mice over extended periods of time. Advanced imaging techniques allowed them to establish the processes during memory formation and recall. The results of their observations are published this week in PNAS Early Edition.

Most of our behavior – and thus our personality – is shaped by previous experience. To store the memory of these experiences and to be able to retrieve the information at will is therefore considered one of the most basic and important functions of the brain. The current model in neuroscience poses that memory is stored as long-lasting anatomical changes in synapses, the specialized structures by which nerve cells connect and signal to each other.

At the Research Institute of Molecular Pathology (IMP) in Vienna, Simon Rumpel and Kaja Moczulska used mice to study the effects of learning and memorizing on the architecture of synapses. They employed an advanced microscopic technique called in vivo two-photon imaging that allows the analysis of structures as small as a thousandth of a millimetre in the living brain.

Using this technology, the neurobiologists tracked individual neurons over the course of several weeks and analysed them repeatedly. They focussed their attention on dendritic spines that decorate the neuronal processes and correspond to excitatory synapses. The analyses were combined with behavioral experiments in which the animals underwent classic auditory conditioning. The results showed that the learning experience triggered the formation of new synaptic connections in the auditory cortex. Several of these new structures persisted over time, suggesting a long-lasting trace of memory and confirming an important prediction of the current model.

Apart from the changes during memory formation, the IMP-scientists were interested in the act of remembering. Earlier studies had shown that memory recall is associated with molecular processes similar to the initial formation of memory. These similarities have been suggested to reflect remodelling of memory traces during recall.

To test this hypothesis, previously trained mice were exposed to the auditory cue a week after conditioning while tracking dendritic spines in the auditory cortex. The results showed that although some molecular processes indeed resembled those during memory formation, the anatomical structure of the synapses did not change. These findings suggest that memory retrieval does not lead to a modification of the memory trace per se. Instead, the molecular processes triggered by memory formation and recall could reflect the stabilization of previously altered or recently retrieved synaptic connections.

The primary goal of elucidating the processes during memory formation and recall is to increase our basic knowledge. Insights gained from these studies might however help us to understand diseases of the nervous system that affect memory. They may also, in the future, provide the basis for treatments that offer relief to traumatized patients.

Memory Reconsolidation

So yesterday I am reading about memory reconsolidation.

The theory goes like this, as far as my layman’s understanding goes:

When things initially happen that it is somehow determined that we will remember, they are stored in this ‘quick-write’ part of our brains called the hippocampus. This part of our brain can change quickly and easily, is more 'mutable’ than the rest.

But this part of the brain has a somewhat limited capacity. After/over about a week, the hippocampus (during sleep?) copies/'trains’ a part of the rest of the brain to remember this memory. So it’s copied into long-term memory, which is relatively fixed. This process is called consolidation. Memories are then retrieved from here when required.

This was how the theory went, until fairly recently. Recently a man called Nader did some research and proposed a second process. His idea was that the process of remembering actually loads the memory back into the hippocampus again, and it then gets re-remembered and then re-consolidated back into long-term memory in the rest of the brain.

Nothing really shocking so far.

Where it gets really crazy is this:

These memories, through the process of re-remembering and re-consolidation, are modified. The process of recollection actually changes the memory and then re-writes it over the previous memory. There’s evidence also to suggest that also the situations and conversations around this remembering 'leak’ sometimes into the memory and get remembered along with it. Perhaps you have experienced talking about something you remember with someone, and then they tell you a similar story, and you end up remembering parts of their story later mixed up with yours.

So the process of remembering renders memories mutable; leaky; mushy.

So memory is like magnetic tape: every time they are played the fidelity degrades slightly.

Or, like Alvin Lucier's I am Sitting in a Room, in which a recording is recorded and re-recorded over and over until you end up with a very different recording.

Or, like the dubiously named game Chinese Whispers.

Given that this is fairly recent science, and isn’t uncontroversial in its field, it seems amusing to note that Sartre already wrote about this. He talks in some depth about how the process of remembering leads him to use words, which then replace his memories of the intense sensations of the event, thereby dulling the memories. A brief excerpt:

For a hundred dead stories there still remain one or two living ones. I evoke these with caution, occasionally, not too often, for fear of wearing them out, I fish one out, again I see the scenery, the characters, the attitudes. I stop suddenly: there is a flaw, I have seen a word pierce through the web of sensations. I suppose that this word will soon take the place of several images I love. I must stop quickly and think of something else; I don’t want to tire my memories. In vain; the next time I evoke them a good part will be congealed.
– Sartre, Nausea.

Reading about all this seems to being about what feels like profound change in my sense of my own existence. I felt a sudden fear or dread upon reading it.

Memory suddenly becomes something that is used up or worn away. The pleasure of memory, of remembering things that have happened, neutral or even happy things, is haunted with loss and death. This way of keeping or saving preciousness, things of which everything else is lost and memories are all you have, now bound up with that process of loss itself… 

A smile, the sound of a laugh, a particular moment spent with someone.

It makes me scared to remember. I feel a memory rise up and then want to quash it immediately to avoid distorting it, save it for when I really want it, to savour it. 

But then, if an instant of it catches, I worry that if I don’t remember it as fully and intensely as I can, the re-remembering will be even more degraded, will be reduced to that scrap of memory I let through. So I shut my eyes, try to block all interference, noise, anything that could leak in, and remember everything I can about it, start to finish.

But maybe that even degrades it more… more surface area for inaccuracies, words over sensations, to sneak in.

The only way out of this seems to be to acknowledge that memories are never perfect copies of experience anyway, they’re already degraded and distorted. Needless to say, this is even less comforting.

Which reminds me of this, which has stayed with me forever:

“Death is always on the way, but the fact that you don’t know when it will arrive seems to take away from the finiteness of life. It’s that terrible precision that we hate so much. But because we don’t know, we get to think of life as an inexhaustible well. Yet everything happens a certain number of times, and a very small number, really. How many more times will you remember a certain afternoon of your childhood, some afternoon that’s so deeply a part of your being that you can’t even conceive of your life without it? Perhaps four or five times more. Perhaps not even. How many more times will you watch the full moon rise? Perhaps twenty. And yet it all seems  limitless.”
– Paul Bowles (The Sheltering Sky)

7. 1996-2001: A Great Time to be in That Great Lab in That Great City

By: Karim Nader, PhD

Dr. Karim Nader runs The Nader Lab at McGill University.

Cool music at that time was Coldplay, Linkin Park, Green Day, The Black Crowes and Radiohead. The cool movies were Trainspotting, Romeo & Juliet, The 5th Element, American History X and Fight Club. The most memorable color changes on the Empire State Building—Princess Diana and Mother Teresa. I was shocked when the Princess’ colors trumped the nun’s for a day. And on September 11, 2001, I watched the world trade centers falling from the roof of my apt with Stu Greenstein.

I spent five years as a postdoc in the LeDoux lab at NYU from 1996 to 2001. Joe’s lab was no less great than the city it inhabited.  At the beginning of the 90’s, the amygdala was known to be involved in Pavlovian aversive conditioning, but how information about the stimuli got to the amygdala had not been studied.  The only known sensory inputs to the amygdala were from cortical areas.    

In a series of killer experiments, now common knowledge to anyone who studies fear conditioning (or, at the time called “fear conditioning”), Joe’s lab reported something that no one had seen before: anatomical evidence for a direct projection from the auditory thalamus to the lateral amygdala. Physiological evidence for this direct projection soon followed. In 1992 Liz Romanski published another paper that made the evidence for an alternative subcortical pathway even stronger. In a stunning test of the functional contributions of these two pathways, Romanski showed that the default pathway for mediation of emotional, aversive conditioning in the brain was through the thalamus, but that in its absence, the cortex could compensate.

Joe had a vision, faith in anatomy and dedication to merging evidence from as many lines of investigation as possible. This way of working is what made his lab’s novel discoveries about the direct pathway in the 90’s so acceptable. Decades later, it would lead to his 2013 initiation into the National Academy of Sciences.

When I arrived at Joe’s lab I was pleasantly surprised to see someone who was incredibly excited about the science in his lab. Beyond that, he was super supportive of his people and allowed them to do what they wanted.  Shortly after I arrived, I asked Joe if I could get more conditioning boxes to test more rats at the same time. I also requested DVD recorders so I could have a digital record of their behavior. I gave him a quote for four boxes. Without hesitation he said, “No worries. Set it up.”  This interaction exemplified his supportive leadership then and now. 

My generation of scientists faced a number of questions when it came to aversive learning in the brain. What neuroanatomical pathways relayed the unconditioned signal to the lateral nucleus of the amygdala?  Did aversive learning in the direct and indirect pathways show long-term potentiation (LTP), and, if so, were the mechanisms similar or different to LTP in the hippocampus?

In the lab, these questions led us to address more specific issues. In 1997, Kilcross, Robbins and Everitt published a stunning paper suggesting that there was not one amygdala circuit for aversive Pavlovian conditioning, but two. We responded to this logically with a commentary in Trends in Cognitive Sciences and experimentally with Prin Amorapanth’s paper in Nature Neuroscience. We suggested a number of testable alternative interpretations, including compensation by the residual fear system and changes in response rates that may have caused changes on the reported suppression ratios. And then, as stated we performed the experiments with Prin.  To this day, I recall Joe’s constant mantra—“it is always better to respond with data than logical arguments.”

This mantra came in handy when it came time to address the backlash over our reconsolidation manuscript.  This finding brought out the worst in most people and the best in a few.  Joe was categorically for a number of reasons.  First, he was open to the new finding and concept.  Of course, I was. And we were both blind-sided by the dogmatic zeal of the backlash.

In 1998 Larry Cahill and Jim McGaugh called the effect pseudoscience in an article in Trends in Neurosciences. They began their piece with a George Santayana quote, “‘those who cannot remember the past are condemned to repeat it.’”  I told Joe the critics didn’t seem to have an alternative interpretation, simply double standards. All the alternative interpretations prosed against reconsolidation were also applicable to consolidation. What this logically meant is that if you believe in consolidation, you must logically believe in reconsolidation (see Nader & Hardt, 2009). 

We held a mini symposium at the SFN 2001 meeting.  Joe, Yadin Dudai, myself, Alcino Silva, Susan Sara, and Jim McGaugh spoke. The venue drew a full house.  McGaugh was not on board. At the end, however, Nobel laureate, Eric Kandel offered a wonderful, spontaneous and positive perspective on our findings from the floor.

When I said we should apply for the Human Frontier Science Program and Volkswagen grants, Joe was, again, open to my proposal. He got in touch with Yadin Dudai, Richard Morris, Tobias Bonheoffer, Randolf Menzel, who all agreed to be part of consortiums to test reconsolidation across species, systems and levels of analyses. Joe insisted I be Principal Investigator on those grants which consistently showed his faith in me and uniqueness as head of a lab. 

*****

My reconsolidation paper was my first paper on memory—Joe could have looked at the backlash and said he would not support the conclusion. He could have applied for grants to investigate the phenomena without me. He, like most other heads of big labs, could have taken the credit.  But he did none of those things. Today I feel very fortunate to have been in Joe’s lab.

To put it in an extreme way, if we are all rewriting our memories every time we recall an event, the memory exists not as a file in our brain but only as the most recent rewrite of a scenario. Every memoir is fabricated, and the past is nothing more than our last retelling of it. Archival memory data is mixed with whatever new information helps shape the way we think—and feel—about it. “My conclusion,” says Schiller, “is that memory is what you are now. Not in pictures, not in recordings. Your memory is who you are now.”

Her Moth/Story Collider Story narrated in her own voice, on the same subject can be found here

youtube

The vid is from 2012. This magazine article is from 2010:

Greg Miller on “Making Memories” (via How Our Brains Make Memories | Science & Nature | Smithsonian Magazine)

“Nader suggests that reconsolidation may be the brain’s mechanism for recasting old memories in the light of everything that has happened since. In other words, it just might be what keeps us from living in the past.”

Reconsolidation as how we remember seems spot on to me. …that we lay down a new memory every time we remember an event, rather than store that old memory pristinely for recall.  We can’t go back to before we knew everything that’s happened since. It’s more important to take the gist of what’s happened to us and distill it into something that we can draw on when we face a similar dilemma in the future.

Repairing Bad Memories

It was a Saturday night at the New York Psychoanalytic Institute, and the second-floor auditorium held an odd mix of gray-haired, cerebral Upper East Side types and young, scruffy downtown grad students in black denim. Up on the stage, neuroscientist Daniela Schiller, a riveting figure with her long, straight hair and impossibly erect posture, paused briefly from what she was doing to deliver a mini-lecture about memory.

She explained how recent research, including her own, has shown that memories are not unchanging physical traces in the brain. Instead, they are malleable constructs that may be rebuilt every time they are recalled. The research suggests, she said, that doctors (and psychotherapists) might be able to use this knowledge to help patients block the fearful emotions they experience when recalling a traumatic event, converting chronic sources of debilitating anxiety into benign trips down memory lane.

And then Schiller went back to what she had been doing, which was providing a slamming, rhythmic beat on drums and backup vocals for the Amygdaloids, a rock band composed of New York City neuroscientists. During their performance at the institute’s second annual “Heavy Mental Variety Show,” the band blasted out a selection of its greatest hits, including songs about cognition (“Theory of My Mind”), memory (“A Trace”), and psychopathology (“Brainstorm”).

“Just give me a pill,” Schiller crooned at one point, during the chorus of a song called “Memory Pill.” “Wash away my memories …”

The irony is that if research by Schiller and others holds up, you may not even need a pill to strip a memory of its power to frighten or oppress you.

Read more

Labile or stable? Opposing consequences for memory when reactivated during waking or sleep

A report published January 23 in Nature Neuroscience concludes that reactivating memories during slow-wave sleep does not involve the same destabilization of the memory as when they are reactivated during a waking state.

In other words, while retrieving memories when you’re awake will actually alter those memories, it seems that sleep has a stabilizing effect, and helps you resist interference in conserving an intact memory.

Here’s the abstract:

Memory consolidation is a dynamic process. Reconsolidation theory assumes that reactivation during wakefulness transiently destabilizes memories, requiring them to reconsolidate in order to persist. Memory reactivation also occurs during slow-wave sleep (SWS) and is assumed to underlie the consolidating effect of sleep. Here, we tested whether the same principle of transient destabilization applies to memory reactivation during SWS. We reactivated memories in humans by presenting associated odor cues either during SWS or wakefulness. Reactivation was followed by an interference task to probe memory stability. As we expected, reactivation during waking destabilized memories. In contrast, reactivation during SWS immediately stabilized memories, thereby directly increasing their resistance to interference. Functional magnetic resonance imaging revealed that reactivation during SWS mainly activated hippocampal and posterior cortical regions, whereas reactivation during wakefulness primarily activated prefrontal cortical areas. Our results show that reactivation of memory serves distinct functions depending on the brain state of wakefulness or sleep.

Read the article in Nature Neuroscience.

(Sources: Technoccult, Wired)

Google, The Memory Banker, Cont'd

Jonah Lehrer ties the Google study I wrote about here to “memory reconsolidation,” or the process by which “[e]very time we recall a memory we also remake it, subtly tweaking the neuronal details. A memory is only as real as the last time you remembered it.”

This notion of mutable, as opposed to static, memory has a lot to do with the type of transactive memory described by Sparrow and her colleagues. Memories are consolidated in response to current experiences through editing and pruning, a process that plausibly optimizes each memory and allows for new ones. But as Lehrer notes, the consequence of this consolidation process is that the frame of reference necessary to evaluate the accuracy of a memory is lost.

Lehrer writes:

“And this is where the internet comes in. One of the virtues of transactive memory is that it acts like a fact-check, helping ensure we don’t all descend into selfish solipsism. By sharing and comparing our memories, we can ensure that we still have some facts in common, that we all haven’t disappeared down the private rabbit hole of our own reconsolidations. In this sense, instinctually wanting to Google information – to not entrust trivia to the fallible brain – is a perfectly healthy impulse. (I’ve used Google to correct my errant memories thousands of times.) I don’t think it’s a sign that technology is rotting our cortex – I think it shows that we’re wise enough to outsource a skill we’re not very good at. Because while the web enables all sorts of other biases – it lets us filter news, for instance, to confirm what we already believe – the use of the web as a vessel of transactive memory is mostly virtuous. We save hard drive space for what matters, while at the same time improving the accuracy of recall.”

More reactions to the aforementioned study below:

Internet Use Affects Memory, Study FindsNew York Times

The Memory GameLapham’s Quarterly

The Extended Mind — How Google Affects Our MemoriesEd Yong, Not Exactly Rocket Science

- yael

My last tiny chunk of fics–copied OFF OF the damn kindle for library reconsolidation purposes in the first place–refuse to reupload to it via Calibre. I right-click, say Send To Device, they send, they briefly are Calibre-searchable as being on the device, then they reappear marked in the Library as not being on the device. I’ve tried converting them to different file formats and trying again and it doesn’t help, they won’t go back on there, they keep jumping back into my main library like fleas.

I’m super mad. >:(