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Electric 'Ripples' in the Resting Brain Tag Memories for Storage
Update: 2024-10-30
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New experiments reveal how the brain chooses which memories to save and add credence to advice about the importance of rest.
The post Electric ‘Ripples’ in the Resting Brain Tag Memories for Storage first appeared on Quanta Magazine
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Transcript
00:00:00
[Music]
00:00:05
Welcome to The Quanta Science Podcast.
00:00:08
Each episode we bring you stories about developments in science and mathematics.
00:00:12
I'm Susan Valette.
00:00:13
New experiments reveal how the brain tags which memories to save.
00:00:18
They add to evidence about the importance of getting sleep.
00:00:21
That's next.
00:00:22
[Music]
00:00:26
It's season three of The Joy of Y, and I still have a lot of questions.
00:00:31
Like, what is this thing we call time?
00:00:33
Why does altruism exist?
00:00:35
And where is Jan 11?
00:00:37
I'm here.
00:00:37
Astrophysicist and co-host.
00:00:39
Ready for anything.
00:00:40
That's right.
00:00:41
I'm bringing in the 18.
00:00:42
So brace yourselves.
00:00:44
Get ready to learn.
00:00:45
I'm Jan 11.
00:00:46
I'm Steve Strogaffs.
00:00:48
And this is Quantum Magazine's podcast The Joy of Y.
00:01:00
New episodes drop every other Thursday.
00:01:03
Yuri Buzaki first started tinkering with waves when he was in high school.
00:01:07
In his childhood home in Hungary, he built a radio receiver, tuned it to various electromagnetic frequencies, and used a radio transmitter to chat with people from around the world.
00:01:18
Most of the time you are talking to strangers, but the goal is to talk to strangers who are in a funny country, what interesting gutters like the Faroe Islands or Tasmania.
00:01:29
Buzaki remembers some of these conversations from his ham radio days better than others, just as you remember only some experiences from your past.
00:01:38
And later on in college, Buzaki found something with similar concepts to ham radio.
00:01:43
I had a very charismatic professor who was talking about the brain, and I realized many of these things are just like, you know, communication, frequencies,
00:01:54
frequency bands, oscillations and so on.
00:01:57
So the brain is like what I know.
00:01:59
So this is basically one day I decided that I wouldn't be a neuroscientist even though the term didn't exist.
00:02:05
Now as a professor of neuroscience at New York University, Buzaki asks questions like "How does the brain decide what to remember?"
00:02:14
By studying electrical patterns in the brain, Buzaki seeks to understand how our experiences are represented and saved as memories.
00:02:23
New studies from his lab and others have suggested that the brain tags experiences worth remembering by repeatedly sending out sudden and powerful high-frequency brainwaves known as sharp wave ripples.
00:02:37
This is what every animal does, when the animal explores the environment, but it's a spider away, rodent, or the tiger.
00:02:43
It's not continuous.
00:02:45
The animals walk and stop, walk and stop.
00:02:48
And the walk and stop is useful because the brain state changes.
00:02:52
And what the essence of it is that the state of the brain should change from one algorithm to an algorithm and that they are supplementing each other.
00:03:00
If you just run one algorithm, you will never learn any kick.
00:03:04
These waves are kicked up by the firing of many thousands of neurons within milliseconds of each other.
00:03:11
Winnie Yang is a doctoral student at Buzaki's lab who knows them well.
00:03:15
She led the new work, which was published in Science and March.
00:03:19
And sharp wave ripples is like a population burst of activity where many neurons, about 20 percent of the neurons in the hippocampus, would very synchronously altogether fire in a very high frequency.
00:03:33
You can think it's like a firework show in the brain where all the cells will just be active together.
00:03:39
They fire when the mammalian brain is at rest, whether during a break between tasks while you're awake or while you're asleep.
00:03:46
And the reason why we're very interested, that's kind of particular event, is like those sharp wave ripples are maybe they're like the electrophysiological container for memory.
00:04:01
And what I mean by that is that during those two states when a sharp wave occurs, they will find sequence of cell firing that is kind of a rehearsal of the previous awake experience.
00:04:15
Sharp wave ripples were already known to be involved in consolidating memories or storing them.
00:04:21
This new research shows that they're also involved in selecting them, pointing to the importance of these waves throughout the process of long-term memory formation.
00:04:31
It also provides neurological reasons why rest and sleep are important for retaining information.
00:04:37
Resting and waking brains seem to run different programs.
00:04:41
If you sleep all the time, you won't form memories.
00:04:44
If you're awake all the time, you won't form them either.
00:04:47
Or as Bijaki says, "This is the most secretive pattern in the mammalian break."
00:04:54
And that's the interesting thing because the hippocampus is telling something very loudly to the rest of the brain that listen to that I'm sending something very important to you.
00:05:02
During those interruptions is when the fireworks go off.
00:05:05
Bijaki will never forget the first time he heard a sharp wave ripple.
00:05:09
It was in 1981.
00:05:11
He was a postdoc at the University of Western Ontario listening to the brain activity of anesthetized rodents through a loud speaker.
00:05:20
After about nine years of research, he had become accustomed to the rhythmic melodic oscillations that sounded as the awake animals explored their environments as he told reporter Yasmin Sapkogu during a visit to his lab.
00:05:33
Everything was in a loud speaker, so I could hear things.
00:05:37
And I really learned before that he found me in the pyramidal area and that he was walking around.
00:05:40
That he could be this very nice later thing.
00:05:45
But then the animals were anesthetized and I hear this bone.
00:05:49
It's a big...
00:05:51
like that.
00:05:52
And they said, "Well, there was probably an artifact somewhere.
00:05:54
And then I hear the gain and the gain and I see what happens.
00:05:58
And I realize that this is a very powerful battle."
00:06:01
What was going on?
00:06:02
The rodents waking brains had generated electrical activity that oscillated at a constant rate.
00:06:08
But when they were anesthetized, their brains seemed to irregularly fire off much faster patterns.
00:06:16
Other researchers had observed the fast waves too.
00:06:19
Bijaki's postdoctoral advisor Cornelius Vanderwolf had described the irregular patterns in 1969.
00:06:27
Nobel Prize-winning neuroscientist John O'Keefe coined the term "ripples" to describe them in the 1970s.
00:06:34
But it wasn't until Bijaki heard them for himself that he became obsessed.
00:06:39
He spent much of his lab time over the next decade trying to characterize these electrical bursts.
00:06:45
In the late 1980s, researchers discovered that they could induce neurons to make stronger interconnections linked to learning a memory by artificially stimulating them to fire in rapid bursts.
00:06:57
To Bijaki, those bursts sounded a lot like his waves.
00:07:02
In 1989, he first hypothesized that sharp wave ripples might be part of the brain's mechanism for forming and consolidating memories.
00:07:12
Michal Zorago is a neuroscientist at the Kuley Shadefronts who worked as a postdoc in Bijaki's lab in 2002.
00:07:20
So he had the idea that this was not some noisy activity but it was relevant for the brain and that possibly this was related to previous weight behavior.
00:07:28
And that was a great anticipation of future discoveries because at the time very little was actually known but what happened during those high frequency oscillations.
00:07:38
In the 1990s and early 2000s, researchers took advantage of improved computing power and new tools that could record electrical activity from more than 100 neurons at once to better characterize sharp wave ripples.
00:07:52
Bijaki and other scientists discovered that the ripples seemed to replay brain activity from an animal's experience, such as running through a maze.
00:08:01
But these replay ripples oscillated 10 to 20 times faster than the original signals.
00:08:07
Here Rolaki Norimoto, a professor of neuroscience at Nagoya University in Japan, says one 2002 paper, which made sharp wave ripples very famous,
00:08:18
found that sharp wave ripples reactivate a sequence of neuronal activity.
00:08:23
In 2009 and 2010, two papers, including one led by Zorago, showed that sharp wave ripples were involved in consolidating memories to endure over a long term.
00:08:35
When researchers suppressed or disrupted the ripples, rats performed worse on memory tasks.
00:08:41
So that was caused by all the rest was coronational, but super important.
00:08:44
It's really important to see that all these patterns occur.
00:08:48
And then when you destroy them, the animal no longer remembers.
00:08:51
Later studies showed that elongating or creating more ripples improved rats' memory.
00:08:57
It became clear that the ripples were playing repeatedly to cement a memory.
00:09:01
Laila Davachi is a professor of psychology at Columbia University.
00:09:05
It's like the brain is rehearsing.
00:09:07
Davachi says even in these moments of wakeful rest, your brain continues to rehearse and replay the past.
00:09:14
Daniel Bindor is a professor of behavioral neuroscience at University College London.
00:09:19
You can think of it as like a melody on the piano.
00:09:21
So you practice the melody and then your brain is another state where it sort of can do random things and all of a sudden you hear that melody.
00:09:30
It can be like when you're pausing after the behavior or it can be when you're sleeping and presumably there's just random activity happening.
00:09:38
So basically a specific sequence of neurons fires to record and experience.
00:09:43
Just as a pianist taps out a specific sequence of keys.
00:09:47
Then during sleep, the hippocampus replays that sequence but faster and potentially hundreds or thousands of times.
00:09:55
The frenetic sharp wave ripples propagate out from the hippocampus, a way station in the brain for episodic memories of particular experiences toward the cortex,
00:10:06
which is involved in long-term memory storage.
00:10:09
However, no one could explain why the ripples propagated while an animal was awake and resting.
00:10:14
Here's Bindor.
00:10:15
And that's where it gets a bit confusing what this could be for.
00:10:18
It's thought maybe it's not memory consolidation because you need to be asleep for that.
00:10:23
So must serve some other purpose.
00:10:25
Scientists said many ideas.
00:10:27
First, those thought it was like planning, decision-making.
00:10:30
They could be taking how the memory is stored and modifying it in some way, reallocating the memory.
00:10:37
Another idea, which several groups proposed, was that the replay while an animal was awake and replayed during sleep were intimately tied.
00:10:46
There's a relationship between which memories have the wake replay, and which memories have the sleep replay.
00:10:55
So the more you have the wake replay, the more you have the sleep replay.
00:10:58
Bujaki had another idea that the ripples could be the mechanism by which the brain chooses what experiences to remember.
00:11:07
At NYU, boxes of resting and sleeping mice sat in an infrared lit room.
00:11:13
In the room next door were handcrafted mazes, constructed from plastic and tape.
00:11:18
One at a time, the mice were placed in the mazes.
00:11:21
They ran around, wearing electrodes that recorded the activity of around 500 hippocampal neurons.
00:11:28
They learned that certain routes would earn them a reward of water.
00:11:32
As they explored the maze, the mice took small breaks to rest or groom themselves.
00:11:38
And after the trials were over, they were returned to their home cage for a snooze.
00:11:43
The researchers continued to record their brain activity as they slept.
00:11:47
Yang analyzed the data by mapping which neurons fired during different trials.
00:11:52
She saw a lot of variation.
00:11:54
Some neurons fired during early trials and others fired during later ones.
00:11:59
Sometimes they fired at different rates.
00:12:01
That told her that the brain recorded an animal's experience of individual trials differently.
00:12:07
Notably, some trials were followed by bursts of sharp-wave ripples while others weren't.
00:12:13
Then she compared the brain activity recorded during the mice's maze experiences to the related ripples that appeared later.
00:12:20
The trials that replayed more frequently as the mice rested were the same trials that replayed as they slept.
00:12:27
And the trials that were not replayed when the mice were awake weren't replayed during sleep either.
00:12:34
The team concluded that the resting ripples might be a mechanism by which the brain prioritizes experiences to remember.
00:12:41
Here's Yang.
00:12:42
The beautiful correlation between awake and sleep ripples really made us think that, okay, maybe awake ripples are those memory tags, such that the memories that are tagged by the awake ripples are special.
00:12:56
And those tagged are going to be selectively replayed many, many more times during sleep and get consolidated.
00:13:05
Meaning consolidated for long-term storage.
00:13:08
On the contrary, those that are not tagged are not replayed during sleep and they will be forgotten.
00:13:17
Or as neuroscientist Mikhail Zorago says, which are the interesting things to remember, because you don't remember everything from your daily life.
00:13:24
There has to be some kind of a triage to remember what is relevant and forget the rest.
00:13:31
Many groups have contributed to outlining all these different mechanisms, but understanding how specific memories were selected for storage was still lacking.
00:13:43
Now we have a good clue.
00:13:45
Last December, a research team led by Bindor at University College London published related results in nature communications that anticipated those of Yang and Bujaki.
00:13:56
They too found that sharp wave ripples that fired when rats were awake and asleep seemed to tag experiences for memory.
00:14:04
However, their analysis averaged a number of different trials together and approached less precise than what Yang and Bujaki accomplished.
00:14:12
The NYU team's key innovation was to bring the element of time into their analysis.
00:14:18
Time distinguishes similar memories from one another.
00:14:22
The mice were running around in the same maze patterns, and yet these researchers could distinguish between blocks of trials at the neuronal level, a resolution never reached before.
00:14:32
Lauren Frank is a neuroscientist at the University of California, San Francisco who wasn't involved in the research.
00:14:39
This idea that there might be greater specificity in these patterns that might actually mark something a little bit closer to an event and a little bit less like a general knowledge of how the environment is connected.
00:14:51
That strikes me as a really interesting finding.
00:14:53
For your all-love starter is a neuroscientist at Ratboud University who also wasn't involved with the work.
00:15:00
Their spin on it really is that it allows the brain to kind of create, let's say, somewhat distinguishable memories for events that happen in the same place,
00:15:11
but at different times, right?
00:15:13
Like you can probably, in your mind, identify multiple times you went to your parents' place, let's say, to visit.
00:15:19
And even though you're in the same place and many of the kind of sensory features of those experiences are kind of overlapping a lot, you can probably also kind of pick apart, like, oh, no, but,
00:15:29
you know, I went there, we were talking about my job or something like that.
00:15:33
And I remember going there another time and my aunt was visiting or something like that.
00:15:37
They're showing that the brain is maybe kind of creating some kind of temporal code, you could say, to distinguish between different memories occurring in the same place.
00:15:48
Shantanu Jadov, a neuroscientist at Brandeis University, praises the study.
00:15:53
I think we still need to do a lot of work, especially in the behavioral domain, but this is a good start to say that, you know, this is one of the possible putative mechanisms.
00:16:02
Jadov hopes to see a follow-up experiment that includes a behavioral test.
00:16:07
In this particular case, we actually do not know that the animals remember those particular trials, right?
00:16:13
So what would be the real proof that this is a tagging mechanism that they are memory of those particular trial blocks and not, and this didn't have a behavioral test, of course.
00:16:21
It's only a physiology test, because if you're saying that, in sleep, you reactivate on this specific episode, so specific trials, then it would be nice if we can,
00:16:31
then test that post-talk, right?
00:16:34
After that process to see, okay, do the animals only remember those trials, it's the experience, but there was nothing unique about any of these trials to do a behavioral test like that, right?
00:16:43
So we have to design different experiments for this.
00:16:45
The research leaves a burning question unanswered.
00:16:48
Why is one experience chosen over another?
00:16:52
The new work suggests how the brain tags a certain experience to remember, but it can't tell us how the brain decides what's worth remembering.
00:17:01
Sometimes the things we remember seem random or irrelevant, and surely different from what we'd select have given the choice.
00:17:08
Neuroscientist Lauren Frank says there's a sense that the brain prioritizes based on importance.
00:17:15
Studies have suggested that emotional or novel experiences tend to be remembered better.
00:17:21
So Frank suggests it's possible that internal fluctuations in arousal, or the levels of neuro modulators, such as dopamine or adrenaline and other chemicals that affect neurons,
00:17:32
end up selecting experiences.
00:17:34
Jodov echoes that thought, saying that the internal state of the organism can bias experiences to be encoded and stored more effectively.
00:17:43
But Jodov says, it's not known what makes one experience more prone to being stored than others.
00:17:49
And in the case of Yang and Bujaki's study, it's not clear why a mouse would remember one trial better than another.
00:17:57
Bujaki remains committed to exploring the rules that sharp wave ripples play in the hippocampus.
00:18:02
Although he and his team are also interested in potential applications that might arise from these observations.
00:18:09
For example, he says it's possible that scientists could disrupt the ripples as part of a treatment for conditions like post-traumatic stress disorder, in which people remember certain experiences too vividly.
00:18:20
The low-hanging crude here is to erase sharp waves and forget what you experienced.
00:18:25
But for the time being, Bujaki will continue to tune in to these powerful brain waves to uncover more about why we remember what we do.
00:18:33
Arlene Santana helped with this episode.
00:18:40
I'm Susan Valette.
00:18:42
For more on this story, read Yasman's "Sapplicot Lose Full" article, electric ripples in the resting brain, tagged memories for storage on our website, quantamagazine.org.
00:18:53
Be sure to tell your friends about the Quanta Science podcast and give us a positive review or follow where you listen.
00:18:59
It helps people find this podcast.
00:19:01
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