The lipids are removed with using a solution of a hydrogel monomer and formaldehyde solution as the first step. Heat is then added to the mix so that the hydrogel monomers are able to polymerize therefore keeping the integrity of the structure to the brain. Then, SDS (sodium dodecyl sulfate) is added to break the lipids apart and remove them from the brain. ETC (Electrophoretic Tissue Clearing) is then used t separate the lipids from the rest of the tissue based on charge/mass.
@@bomchoi2536 perhaps it’s because, to make them visible (soma and axon), they used specific radioactive tracer techniques (in this case the color of the substance used was green), I suppose.
We have the capacity to generate prescient ideas, we have the hypothesis, we have the theorems, but we don't have the means to test, observe or quantify many of them..... until now. Techniques like this allow us to blow apart ambiguity, expose fact and tap in to rich, glorious knowledge.
Thank you Karl Deisseroth for this huge leap in neuroscience!! You are simply a genius and everyone at the University of Toronto neuroscience program is going nuts about the new paper/video. CLARITY is breathtaking
It is a see-through brain, watch again (at 1:33) for the mouse's brain that had been treated. All the fat had been removed and all that was left was grey matter suspended in hydrogel. You could actually look through to read the printed text on the sheet underneath the brain. The colourful graphics just illustrate the markers used to see the three dimensional structures of the brain.
My youngest son (4) has autism. It is my hope that science such as this will help us to one day better understand why autism develops, and perhaps how it can be avoided, or even shed light on how to help these individuals learn in their own unique ways to live independent lives.
This is stellar. I am 34, what we had 20 years ago to now is absolutely staggering. This is so amazing to be able to see the brain. How flipantly they just kind of point out "Oh this may be one of the major symptoms of Autism" is amazing. Imagine; for a second, where this will be when combined with other mapping and man/machine interfaces in say 20 years. I am just blown away at the casualness of these discoveries now. Wow. Just wow
you can get the paper on the website of Karl Deisseroth one of the authors of Stanford University. I can not put here because youtube will not let me put Internet sites.
If you're a college student then your library almost certainly has a subscription to Nature. Just ask your librarian how to access it, a portion of you tuition goes towards paying for such subscriptions. You probably can do it through your library website without even leaving your chair.
While it's not possible to do this in living tissues, what you can do is study the components of the organ, trying to understand "what went wrong" there. What the technique will do is revolutionize the way we study brain pathways related pathology
If you can replace the fat with a different insulating but see-through material without disrupting connections... Highly unlikely. However, this technique used in conjunction with optogenetics (i.e. after optogenetics experiments performed, use clarity to acquire detailed map) has very exciting possibilities!
AuSands1 Absolutely impossible on live subjects. This technique replaces the cell's membrane with a gel. Removal of the membrane completely destroys any chance for the cell's survival.
What bad? No need to apologize! My response intent was to just gave you some factual information! No judgement intended, at all. I did not vote your comment out by the way! That is inappropriate.
That day will come, I'm sure. Today the systems that can generate images of a whole body cannot give you this level of detail. This is the best human technology can do right now. Second important step will be the computers: the scans shown are probably in the TB (1000 GB) range when being acquired: for this you already need the best computers and software available to create the images. For a whole body you might need computers that can handle a million times more data a million times faster!
"The brain is a world consisting of a number of unexplored continents and great stretches of unknown territory." Santiago Ramón y Cajal a.k.a. neuroscience legend/ bawse
Well not really. These brains are almost certainly fixed before the lipid bilayers are stripped. When you want to remove the lipid bilayers in vivo (in the case of optogenetics) you'd disrupt the functionality of the cells.
But looking at the structure is a first big step into discovering this issues. Some might not have structural causes, but we are only capable to tell, if we can rule it out by observation. Until now we had no chance to see it that way.
This is beautyful! If it can be extended to living and operating organisms not only the structure but also the processing synapsis could be observed in the whole system.
Fascinating! this makes me think of the work that's being done isolating the collagen structure of organs and re-growing tissues over them - they look similarly transparent in the 'scaffolding' stage. But this - I never dreamed this was possible! Truly amazing work.
I just voted it up... I guess somebody took issue with the wording "kill the patient" when what you meant to say is "person should be dead first". The question is totally valid though and I was wondering it myself, I read and confirmed it requires a dead brain.
Unfortunately, this hydrogel process can only be done ex vivo, so not much use for the living and optogenetically inclined :/. Great for neuroanatomy though!
Here is the paper: Structural and molecular interrogation of intact biological systems Kwanghun Chung, et al Nature (2013) doi:10.1038/nature12107 it is not free access.
Yes, definitely - it's very invasive. To image a living brain, one needs a scanner of some type, like an MRI or PET scanner. MRI has better resolution than PET, but neither has the type of resolution this technique can achieve.
Why not? This could be the way we figuring out what goes wrong in a brain, ...the missing piece to trace back and use diagnostic techniques to find out what to look for in the living. Imagine being able to literally look straight into a tumor (which could be removed from a living person), or a brain with Alzheimers. Non-invasive Computer imaging goes very far, in particular MRIs.. however the human eye or a high definition camera can see much clearer. This is just incredible...
Unfortunately it doesn't work like that. Synaptic dynamics between each human is different and is affected by a whole slew of environmental factors that can also be traced to optogenetics. Mapping sections of the brain has already been done in terms of showing which part of the brain is responsible for what, but being able to map microcircuits isn't that easy.
wonderful technology! I wonder how they manage to keep the structure of the brain and neural connections from destruction, incl. from decomposition And how well do you manage to keep the structure?
and where do they us these tools? What if I have a very complex neurological illness that all current tests fail to detect. Where would I find someone with this?
The lipids are removed with using a solution of a hydrogel monomer and formaldehyde solution as the first step. Heat is then added to the mix so that the hydrogel monomers are able to polymerize therefore keeping the integrity of the structure to the brain. Then, SDS (sodium dodecyl sulfate) is added to break the lipids apart and remove them from the brain. ETC (Electrophoretic Tissue Clearing) is then used t separate the lipids from the rest of the tissue based on charge/mass.
Paul B Why are the neurons projected green? Arent they supposed to be transparent as well??
@@bomchoi2536 perhaps it’s because, to make them visible (soma and axon), they used specific radioactive tracer techniques (in this case the color of the substance used was green), I suppose.
@@TheClakki oh thanks!! Are you studying this field?? I forgot about this comment!
@@bomchoi2536 Yeah, in some way.
I’m studying neuroscience and psychobiology, that’s why I know a little on this field and techniques.
Nice
This is by far one of the coolest things science has accomplished!
We have the capacity to generate prescient ideas, we have the hypothesis, we have the theorems, but we don't have the means to test, observe or quantify many of them..... until now.
Techniques like this allow us to blow apart ambiguity, expose fact and tap in to rich, glorious knowledge.
I don't understand why did three people dislike this?? please explain!! As for me I give it a "SUPERLIKE"
Thank you Karl Deisseroth for this huge leap in neuroscience!! You are simply a genius and everyone at the University of Toronto neuroscience program is going nuts about the new paper/video. CLARITY is breathtaking
Nice
It is a see-through brain, watch again (at 1:33) for the mouse's brain that had been treated. All the fat had been removed and all that was left was grey matter suspended in hydrogel. You could actually look through to read the printed text on the sheet underneath the brain. The colourful graphics just illustrate the markers used to see the three dimensional structures of the brain.
Clarity deserves nobel prize in 2014
I agree.
Agreed
Amazing research. We are living in an exciting time.
this definitely shows a much more detailed look into the mystery of our own bodies.
My youngest son (4) has autism. It is my hope that science such as this will help us to one day better understand why autism develops, and perhaps how it can be avoided, or even shed light on how to help these individuals learn in their own unique ways to live independent lives.
excellent. Some clearing agents have been going around these past years, but the clearing speed and resolution are superior. congratulations.
This is stellar. I am 34, what we had 20 years ago to now is absolutely staggering.
This is so amazing to be able to see the brain. How flipantly they just kind of point out "Oh this may be one of the major symptoms of Autism" is amazing.
Imagine; for a second, where this will be when combined with other mapping and man/machine interfaces in say 20 years.
I am just blown away at the casualness of these discoveries now.
Wow. Just wow
you can get the paper on the website of Karl Deisseroth one of the authors of Stanford University. I can not put here because youtube will not let me put Internet sites.
This is absolutely incredible.
If you're a college student then your library almost certainly has a subscription to Nature. Just ask your librarian how to access it, a portion of you tuition goes towards paying for such subscriptions. You probably can do it through your library website without even leaving your chair.
While it's not possible to do this in living tissues, what you can do is study the components of the organ, trying to understand "what went wrong" there. What the technique will do is revolutionize the way we study brain pathways related pathology
Definitely needed to see this in the middle of grueling exam week- reminds me that it's all gonna be worth it at the end :)
what are you now?
Beautiful. Simply beautiful.
This is the sexiest thing I've ever seen on youtube.
wow, extremely impressive! one easily recognizes the frame and scale bar of the imaris software, rendering so fast and smoothly.
Deisseroth has done it again! Kudos!
Amazing work...The brain visualisation in this video were created using 'Imaris' software from Bitplane.
That was absolutely awesome and beautiful to watch. Well Done Ladies and Gentlemen. Well done.
If you can replace the fat with a different insulating but see-through material without disrupting connections... Highly unlikely. However, this technique used in conjunction with optogenetics (i.e. after optogenetics experiments performed, use clarity to acquire detailed map) has very exciting possibilities!
From what I've heard this can be accomplished on live subjects as well enabling them to see thoughts and brain activity as it happens.
AuSands1 Absolutely impossible on live subjects. This technique replaces the cell's membrane with a gel. Removal of the membrane completely destroys any chance for the cell's survival.
Alyss Flynn
Thanks!!!
This is a gamechanger.
It's spectacular neuroscience. I am very fascinated!
optogenetics works in vivo. This technique would not work in live animals. I think misconstrued the two.
Thanks Hilda cerdeira:)
This will get us to the next level for sure!
Absolutely amazing. Although It's a shame we can't get this sort of visualisation on brain tissue that is alive. Well maybe one day...
I guess you could say...
*puts on black sunglasses*
They were reading his mind.
YEAAAAAAAAAAAAAAAAAAAAAAAAH
This is a great tool for research.
Best visualization sofar, along with flash and freeze electron microscopy.
What bad? No need to apologize! My response intent was to just gave you some factual information! No judgement intended, at all. I did not vote your comment out by the way! That is inappropriate.
That day will come, I'm sure. Today the systems that can generate images of a whole body cannot give you this level of detail. This is the best human technology can do right now. Second important step will be the computers: the scans shown are probably in the TB (1000 GB) range when being acquired: for this you already need the best computers and software available to create the images. For a whole body you might need computers that can handle a million times more data a million times faster!
I totally agree with you on the 'in vivo' issue. But I am also optimistic that the technique will drastically improve 10 years down the line.
did it?
"The brain is a world consisting of a number of unexplored continents and great stretches of unknown territory."
Santiago Ramón y Cajal a.k.a. neuroscience legend/ bawse
Well not really. These brains are almost certainly fixed before the lipid bilayers are stripped. When you want to remove the lipid bilayers in vivo (in the case of optogenetics) you'd disrupt the functionality of the cells.
I can see clearly now....the brain has gone ;0)
ok that was funny!
i love the reference...my wife is just rolling her eyes over my stupid humor...
Haha
But looking at the structure is a first big step into discovering this issues. Some might not have structural causes, but we are only capable to tell, if we can rule it out by observation. Until now we had no chance to see it that way.
I can see clearly now, the brain has "gone", it's gonna be a bright, bright sunshiny day
Yes, Mitch, only on dead brains, but you can probably use this technique on other tissues too, you are not limited to the brain.
This isn't a see-through brain - this is how to see through a brain (using clever imaging techniques). Very different things.
That was astonishing.
Inspiring and fascinating!
If you can peer into my mind with that technology you'll never quit me
Future implications for such a technology are grand.
Best visualization of the brain I have seen!!!
This is beautyful! If it can be extended to living and operating organisms not only the structure but also the processing synapsis could be observed in the whole system.
Your college library. Most large public libraries will also have a subscription to Nature.
It is really amazing how we visualize the miracle of nature
Fascinating! this makes me think of the work that's being done isolating the collagen structure of organs and re-growing tissues over them - they look similarly transparent in the 'scaffolding' stage. But this - I never dreamed this was possible! Truly amazing work.
This is simply... Amazing!
cool cool cool, can't wait to see this being used on other organs, and in combo with organ printing.
Can this be used to create a complete map of the human brain? Let's map all the connections and simulate it.
AMAZING!!!
but still remain structure↔function correlation problems
and emergent properties of the MIND...
So freaking Amazing! I had dreams that this would eventually happen. I just want to go back to school and focus on neuroscience.
Hence the word 'potentially'!
Increíble. Me encanta haber nacido en esta época.
So mapping the brain slice by slice was a waste of time?
That's a relief.
so if our cells didn't have membranes made of fat we would be transparent?
I just voted it up... I guess somebody took issue with the wording "kill the patient" when what you meant to say is "person should be dead first". The question is totally valid though and I was wondering it myself, I read and confirmed it requires a dead brain.
One step closer to understanding the human brain :)
Unfortunately, this hydrogel process can only be done ex vivo, so not much use for the living and optogenetically inclined :/. Great for neuroanatomy though!
Here is the paper:
Structural and molecular interrogation of intact biological systems
Kwanghun Chung, et al
Nature
(2013)
doi:10.1038/nature12107
it is not free access.
This is fascinating, and exciting, this is science, and art, and that's why I love it so much. Thanks a lot for sharing this!
I feel if you couldn't use this with optogenetics because I don't know if you could make the brain transparent in-vivo.
FANTASTIC Science rocks
Yes, definitely - it's very invasive. To image a living brain, one needs a scanner of some type, like an MRI or PET scanner. MRI has better resolution than PET, but neither has the type of resolution this technique can achieve.
Why not? This could be the way we figuring out what goes wrong in a brain, ...the missing piece to trace back and use diagnostic techniques to find out what to look for in the living. Imagine being able to literally look straight into a tumor (which could be removed from a living person), or a brain with Alzheimers. Non-invasive Computer imaging goes very far, in particular MRIs.. however the human eye or a high definition camera can see much clearer. This is just incredible...
Unfortunately it doesn't work like that. Synaptic dynamics between each human is different and is affected by a whole slew of environmental factors that can also be traced to optogenetics. Mapping sections of the brain has already been done in terms of showing which part of the brain is responsible for what, but being able to map microcircuits isn't that easy.
HOLY COW! I mean, MOUSE! And I missed this by... 9 years?? How come all the newer brain videos don't show clarity such as this? (pun intended)
When I go, I might leave my brain so that scientists and doctors might be able to do the same thing with mine.
this soundtrack is so lit I can't even pay attention
What music is this? Amazing science btw.
See end of video
Duh. Thank you.
This makes me happy
While this looks really neat, most of the things mentioned in this video have been possible decades ago with simple histological smears.
Cómo? CLARITY usa células muertas.... Se fijan con acrilamida y se disuelven las grasas con SDS, ¿Cómo aplicas optogenética en eso?
Mind blowing (literally)
Does anyone know what music is playing in the background?
I am looking for the paper where it is being published with the supplementary material, Can someone help me here?
Can't believe only 30 poeple recently had a paper rejected in Nature!
how the sweet flying fuck can someone dislike this video?
one of the most exciting videos i've seen in years!
GO SCIENCE!
ok science, there is no limit with human beings
Exciting result!
wonderful technology!
I wonder how they manage to keep the structure of the brain and neural connections from destruction, incl. from decomposition
And how well do you manage to keep the structure?
it is awesome what this world is reaching in technology
That's awesome imagery of the #humanbrain and a rat brain - impressive resolution, clarity, and quality. #BrainResearch .
well done! amazing idea
This is a huge step.
The first step towards the positronic brain.
Pretty kewl,,,,,as long as it's used for good.
There are exhibitions of plastinated human bodies all over the world. It would pretty much looks the same.
who else got goosebumps watching the brainstem like never before..?
This reminds me of the book Invisible Man by H.G Wells. The idea is entertaining.
and where do they us these tools? What if I have a very complex neurological illness that all current tests fail to detect. Where would I find someone with this?
So, the fat is dissolved while the rest of the brain is held in "Hydrogel". Imagine the uses in forensics! :D
Yeah, I should get back to reading my copy of "Neuroscience: Exploring the Brain" It's one thing to mean to study and another to get round to it :/
Absolutely amazing. E-brains here we come!
I love science