Practice Makes Perfect: Crystallized Memory Formation Explored

Summary: A new study confirms the age-old adage “practice makes perfect.” Researchers used cutting-edge technology to observe 73,000 neurons in mice as they learned a task. They found that repetitive practice solidifies neural pathways, transforming unstable memory representations into stable ones, leading to improved performance and mastery.

Key Facts:

  • Repetitive practice strengthens and stabilizes neural pathways in the brain.
  • This “crystallization” of memory circuits improves accuracy and automaticity of learned skills.
  • The study used innovative light-beads microscopy to visualize neuronal activity in real time.pen_spark

Source: Rockefeller University

“Practice makes perfect” is no mere cliché, according to a new study from researchers at The Rockefeller University and UCLA. Instead, it’s the recipe for mastering a task, because repeating an activity over and over solidifies neural pathways in your brain.

As they describe in Nature, the scientists used a cutting-edge technology developed by Rockefeller’s Alipasha Vaziri to simultaneously observe 73,000 cortical neurons in mice as the animals learned and repeated a given task over two weeks.

This shows a brain.
They found that the working memory circuits transformed as the mice mastered the proper sequences. Initially, the circuits were unstable, but as the mice practiced the task repeatedly, the circuits began to stabilize and solidify. Credit: Neuroscience News

The study revealed that memory representations transform from unstable to solid in working memory circuits, giving insights into why performance becomes more accurate and automatic following repetitive practice.

“In this work we show how working memory—the brain’s ability to hold and process information—improves through practice,” says Vaziri, head of Rockefeller’s Laboratory of Neurology and Biophysics.

“We expect that these insights will not only advance our understanding of learning and memory but also have implications for addressing memory-related disorders.”

Imagining challenges

Working memory is essential to a variety of cognitive functions, and yet the mechanisms underlying memory formation, retention, and recall—which enable us to perform a task we’ve done before without having to learn it anew—remain unclear over long timescales.

For the current study, the researchers wanted to observe the stability of working memory representations over time, and what role these representations played in the ability to skillfully perform the task on cue.

To do so, they sought to record neuronal populations repeatedly in mice over a relatively long period while the animals learned and became experts in a given task.

But they faced a daunting challenge: technical limitations have hampered the ability to image the activity of large population of neurons across the brain in real time, over longer periods, and at any tissue depth in the cortex.

The UCLA researchers turned to Vaziri, who has developed brain imaging techniques that are among the only tools capable of capturing the majority of the mouse cortex in real time at a high resolution and speed.

Vaziri suggested they use light-beads microscopy (LBM), a high-speed volumetric imaging technology he developed that allows for cellular resolution in vivo recording of activity of neuronal populations up to 1 million neurons—a 100-fold increase in the number of neurons that can be simultaneously recorded.

Neural transformations

In the current study, the researchers used LBM to image the cellular activity of 73,000 neurons in mice simultaneously throughout various depths of the cortex and tracked the activity of the same neurons over two weeks as the animals identified, recalled, and repeated a sequence of odors.

They found that the working memory circuits transformed as the mice mastered the proper sequences. Initially, the circuits were unstable, but as the mice practiced the task repeatedly, the circuits began to stabilize and solidify.

“This is what we refer to as ‘crystallization,’” Vaziri says. “The findings essentially illustrate that repetitive training not only enhances skill proficiency but also leads to profound changes in the brain’s memory circuits, making performance more accurate and automatic.”

“If one imagines that each neuron in the brain is sounding a different note, the melody that the brain is generating when it is doing the task was changing from day to day, but then became more and more refined and similar as animals kept practicing the task,” adds corresponding author and UCLA Health neurologist Peyman Golshani.

Crucially, some aspects of these discoveries were uniquely enabled by the large-scale and deep tissue imaging capabilities of LBM. Initially, the researchers used standard two-photon imaging of smaller neuronal populations in upper cortical layers, but they failed to find evidence for memory stabilization.

But once they employed LBM to record from over 70,000 neurons in deeper cortical regions, they were able to observe the crystallization of working memory representations that accompanied the mice’s increasing mastery of the task.

“In the future, we may tackle the role of different neuronal cell types involved in mediating this mechanism, and in particular the interaction of different types of interneurons with excitatory cells,” Vaziri says.

“We’re also interested in understanding how learning is implemented and could be transferred into a new context—that is, how the brain could generalize from a learned task to some new unknown problems.”

About this memory research news

Author: Katherine Fenz
Source: Rockefeller University
Contact: Katherine Fenz – Rockefeller University
Image: The image is credited to Neuroscience News

Original Research: Open access.
Volatile working memory representations crystallize with practice” by Alipasha Vaziri et al. Nature


Volatile working memory representations crystallize with practice

Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions.

However, the mechanisms underlying the generation and evolution of working-memory neuronal representations at the population level over long timescales remain unclear.

Here, to identify these mechanisms, we trained head-fixed mice to perform an olfactory delayed-association task in which the mice made decisions depending on the sequential identity of two odours separated by a 5 s delay.

Optogenetic inhibition of secondary motor neurons during the late-delay and choice epochs strongly impaired the task performance of the mice.

Mesoscopic calcium imaging of large neuronal populations of the secondary motor cortex (M2), retrosplenial cortex (RSA) and primary motor cortex (M1) showed that many late-delay-epoch-selective neurons emerged in M2 as the mice learned the task.

Working-memory late-delay decoding accuracy substantially improved in the M2, but not in the M1 or RSA, as the mice became experts.

During the early expert phase, working-memory representations during the late-delay epoch drifted across days, while the stimulus and choice representations stabilized.

In contrast to single-plane layer 2/3 (L2/3) imaging, simultaneous volumetric calcium imaging of up to 73,307 M2 neurons, which included superficial L5 neurons, also revealed stabilization of late-delay working-memory representations with continued practice.

Thus, delay- and choice-related activities that are essential for working-memory performance drift during learning and stabilize only after several days of expert performance.

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  1. Speaking as someone who is both autistic and has ADHD, I am moved to write and tell the non-ADHD (that is to say, “neurotypical”) world that you have grossly misrepresented and underexplained “practice” to us, and as a result both we and you have probably been frustrated, more than a time or two, by the experience of an ADHD child, partner, or colleague, practicing a thing for a very long time without ever getting any better at it.

    Whether the thing being practiced is a paperwork procedure or the schoolyard act of hitting a ball with a stick, our experience, more often than not, is 10,000 repetitions of doing the thing without ever getting any better at it. This is so common that I recently saw a Facebook meme about it. It’s frustrating for us (at age 60 I still cannot hit a thrown ball with a stick) and for you (that one guy in the office who simply can’t master the job after working there for years). But as a scientist able to step outside the box and conjecture about what neurotypicals may be omitting, I may have a solution.

    What the neurotypical world has failed to realize is that the AuDHD brain interprets the word practice as mere repetition — mainly because that’s how you’ve explained it to us. “Just keep doing it over and over again until you get it.” However, our natural instinct, our natural priority, is to specifically constrain ourselves to do the thing exactly the same way every time, to a degree of hyperfocused uberprecision that apparently the neurotypical instructor can’t even conceive of. If we do it one particular completely wrong way the first time, we will continue to do it exactly that same particular completely wrong way each and every one of the 9,999 times after that, because that, we believe, is what we have been told to do: repeat what you are doing. So we repeat it, with no variation at all because THAT’S WHAT “REPEAT” MEANS.

    Except that it doesn’t. That’s not what repeat is supposed to mean in this context. In this specific context, repeat turns out to me, with slight variations – – in the case of hitting a ball, perhaps with slight fluctuations in arm tension, timing, stance, attention to ball versus stick, and God knows what all else — with the idea being that eventually we will magically and accidentally hit upon exactly the right combination of these thousands of variables that lets us accomplish the task better than we did it first — in my case, I might eventually actually hit the ball.

    But my point is that you, the neurotypical teacher or instructor, have to explain ALL THIS TO US. You have to tell us explicitly that we’re not supposed to “repeat it exactly and identically the same way forever,” because what doesn’t work on swing number one isn’t going to work any better on swing number 10,000. You have to tell us explicitly that we are supposed to vary what we’re doing, AND EXPLICITLY LAY OUT FOR US the thousand variables we should try varying. This might even need to come down to such fine-grained things as “try different sequences of muscle tensioning patterns in the course of moving our arms and upper body to swing at the ball.” Every single goddamn fine grained variation on the process you could possibly think of, including stuff you would swear nobody would ever think of or think about, because believe me, we do. If my wrist feels a little funny when I try to hit the ball a certain way, I am immediately going to be thinking of the entire intricacy of human arm anatomy, including the structure of my bones, attachment of my ligaments, the multitude of neuromuscular disorders that could be interfering with transmission of signals to my muscles, for the contraction of my muscles in response to those signals, and on and on and on ad ifinitum. How the hell do _I_ know why I can’t hit that ball? The reason could be ANYTHING, including 10,000 things you are not well-read enough to think about, but I am.

    That’s not even much of an exaggeration. I can’t flip the light switch without thinking about electrons and conductivity in the properties of materials that make some things insulators and others conductors. Trying to hit a ball is just more of the same, but in an arena where I know a lot less about things than I do about electrons and The conductivity of materials. That’s life inside my brain.

    What we need you neurotypicals to do for us is explain the scope of the situation and the scenario. How likely is it that a neuromuscular disorder is interfering with my ability to hit that ball? Is it more likely something else? What exactly does it mean to adjust my stance? At what precise angle, velocity, and timing am I supposed to move the stick in order to hit the ball? I don’t learn those things by watching other people do it, I need it explained in words, possibly in terms of the scientific terms of mechanics and physics. If you can’t put it in words, or in those words, maybe you’re the wrong instructor for me. The point is, you need the patience of a saint and the inside of a genius, to understand what’s going on inside of our neurotypical minds and spot where we are running off the rails based on the incompleteness of the explanations that suffice for normal people who understand how to fill in the gaps and what the implicit limits and expectations of the process are. Ordinary people would probably never expect, therefore would never try, to do the exact same thing when swinging that stick, because they simply have never been capable of doing it exactly precisely the same way 10,000 times in a row. They know, expect, and accept and assume, the variations will creep in and eventually lead to them hitting the ball, and that then I can try to figure out what was different about that particular try that made it successful when the other 9,998 times were not. For us it’s the other way around. You have to specify all the things to try doing differently, upfront, give us permission and encouragement and the understanding that we are supposed to ALLOW WHAT WE’RE DOING TO VARY a little bit, though not too much, around a sort of overall center point in the multi-dimensional space that describes the trajectory of a stick trying to hit a ball. Or whatever it is we are trying to do.

    Taking a little deeper, another idea occurs to me. It is well known that introducing visual noise to a blurry photograph makes it look sharper, because of error-correcting features in the human visual system. Perhaps something similar might help me learn to hit a ball. Perhaps what I need is for someone to grab my shoulders and shake me, while I’m trying to hit the ball, introducing a bit of variation I am unable to introduce on my own. I don’t know for a fact that that would help, but it wouldn’t surprise me at all if the results were very different in my case then they would be in the case of a neurotypical person.

    Anyway, to sum up, I think this is a special case of something neurotypicals often don’t understand about us AuDHD (or otherwise neurodivergent) folk: often, we need stuff spelled out that you neurotypicals take for granted without even realizing you’re doing so. So we’d appreciate it if you’d learn to think that way and try it.

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