A map of the brain: Allan Jones at TEDxCaltech
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0:09 - 0:11Complexity.
-
0:11 - 0:15Nothing quite embodies this word
like the human brain. -
0:15 - 0:20So for centuries we've studied
the complexity of the human brain -
0:20 - 0:23using the tools and technology of the day,
-
0:23 - 0:27if that's pen and paper
from the age of da Vinci, -
0:27 - 0:30through advents in microscopy
-
0:30 - 0:33to be able to look more deeply
into the brain, -
0:33 - 0:36to a lot of the new technologies
that you've heard about today -
0:36 - 0:39through imaging,
magnetic resonance imaging, -
0:39 - 0:42able to look at the details of the brain.
-
0:42 - 0:44Now one of the first things
you notice when you look -
0:44 - 0:49at a fresh human brain
is the amount of vasculature -
0:49 - 0:51that's completely covering this.
-
0:51 - 0:56The brain is this metabolically
voracious organ. -
0:56 - 1:01Approximately a quarter
of the oxygen in your blood, -
1:01 - 1:05approximately a fifth
of the glucose in your blood -
1:05 - 1:07is being used by this organ.
-
1:07 - 1:10It's so metabolically active,
there's a waste stream -
1:10 - 1:13which comes out
into your cerebral spinal fluid. -
1:13 - 1:18You generate 0.5 liter of CSF every day.
-
1:18 - 1:22So, as you know, researchers
have taken advantage -
1:22 - 1:25of this massive amount of blood flow
and metabolic activity -
1:25 - 1:30to begin to map regions of the brain,
to functionally annotate the brain -
1:30 - 1:31in very meaningful ways.
-
1:31 - 1:34You'll hear a lot more
about those kinds of studies, -
1:34 - 1:38but basically taking advantage of the fact
that there's active metabolism -
1:38 - 1:40with certain tasks going on.
-
1:40 - 1:42You can put a living human in a machine
-
1:42 - 1:44and you can see various areas
that are lighting up. -
1:44 - 1:48For example, going around right now
is the temporal cortex, -
1:48 - 1:51auditory processing going on there,
you're listening to my words, -
1:51 - 1:53you're processing what I'm saying.
-
1:53 - 1:57Moving to the front of this brain
is your prefrontal cortex, -
1:57 - 1:59your executive decision-making,
-
1:59 - 2:02your higher-thinking areas of the brain.
-
2:02 - 2:08And so the thing that
we're very much interested in -
2:08 - 2:11from the perspective
of the Allen Institute -
2:11 - 2:14is to go deeper,
to get down to the cellular level. -
2:14 - 2:18So when you look at this slice, it doesn't
really look like gray matter, does it? -
2:18 - 2:21It's more tan matter, or beige matter.
-
2:21 - 2:26And scientists about, I guess
around the late 1800's, -
2:26 - 2:29discovered that they could
stain tissue in various ways, -
2:29 - 2:33and this sort of came along
with various microscopy techniques. -
2:33 - 2:37And so this is a stain, it's called Nissl,
and it stains cell bodies, -
2:37 - 2:41it stains the cell bodies purple.
-
2:41 - 2:44And so you can see
a lot more structure and texture -
2:44 - 2:46when you look at something like this.
-
2:46 - 2:50You can see the outer layers of the brain
and the neocortex, -
2:50 - 2:55there's a six-layer structure, arguably
what makes us most uniquely human. -
2:55 - 2:59As you've heard before about
there's on average in a human, -
2:59 - 3:04there's about 86 billion neurons,
and those 86 billion neurons -
3:04 - 3:06you can see are not evenly distributed,
-
3:06 - 3:09they're very focused
in specific structures. -
3:09 - 3:12And each of them
has their own sort of function, -
3:12 - 3:15both on an anatomic level
and at a cellular level. -
3:15 - 3:20So if we zoom in on these cells,
what you can see is large cells -
3:20 - 3:23and small support cells
that are glials and astrocytes -
3:23 - 3:28and these cells are as we know
connected in a variety of different ways. -
3:28 - 3:32And we like to think about,
although there's 86 billion cells, -
3:32 - 3:36each cell might be considered a snowflake,
they're actually able to be binned -
3:36 - 3:40into a large number
of cell types or classes. -
3:40 - 3:44What flavor of activity
that particular cell class has -
3:44 - 3:49is driven by the underlying genes
that are turned on in that cell, -
3:49 - 3:53those drive protein expression
which guide the function of those cells, -
3:53 - 3:56who they're connected to,
what their morphology is, -
3:56 - 4:00and we're very much interested
in understanding these cell classes. -
4:00 - 4:02So how do we do that?
-
4:02 - 4:06Well, we look inside the cell
at the nucleus, -
4:06 - 4:08-- and it will get to the nucleus --
-
4:08 - 4:11and so inside we've got
23 pairs of chromosomes, -
4:11 - 4:13got a pair from mom, a pair from dad,
-
4:13 - 4:18on those chromosomes about 25,000 genes
and we're very much again interested in -
4:18 - 4:22understanding which
of these 25,000 genes are turned on -
4:22 - 4:24at what levels they're turned on.
-
4:24 - 4:28Those are going to, of course, drive
the underlying biochemistry of the cells -
4:28 - 4:33they're turned on in and again every cell
in our bodies more or less has these -
4:33 - 4:35and we want to understand better
-
4:35 - 4:42what the driving biochemistry
driven by our genome is. -
4:42 - 4:45So how do we do that?
-
4:48 - 4:51We're going to deconstruct a brain
in several easy steps. -
4:51 - 4:54So we start
at a medical examiner's office. -
4:54 - 4:57This is a place
where the dead are brought in -
4:57 - 4:59and obviously as you saw before
-
4:59 - 5:03for the kind of work we do,
[it] is not non-invasive, -
5:03 - 5:09we actually need
to obtain fresh brain tissue -
5:09 - 5:13and we need to obtain it within 24 hours
because the tissues start to degrade. -
5:13 - 5:16We also wanted for our projects
to have normal tissue, -
5:16 - 5:19as much normal as we could possibly get.
-
5:19 - 5:25So over the course of a two-
or three-year collection time window -
5:25 - 5:31we collected 6 very high-quality brains,
5 of them were male, 1 was female. -
5:31 - 5:36That's only because males
tend to die untimely deaths -
5:36 - 5:40more frequently than females,
and then to add to that, -
5:40 - 5:43females are much more likely
to give consent -
5:43 - 5:46for us to take the brain than vice versa.
-
5:46 - 5:49We have to figure that one out.
-
5:49 - 5:53We've heard people say,
"He wasn't using it anyway!" -
5:53 - 5:55(Laughter)
-
5:57 - 6:01So, once the brain comes in
we have to move very, very quickly. -
6:01 - 6:06So first we capture
a magnetic resonance image. -
6:06 - 6:09This, of course,
will look very familiar to you, -
6:09 - 6:12but this is going to be the structure
in which we hang all this information, -
6:12 - 6:16it's also a common coordinate framework
by which the many, many researchers -
6:16 - 6:17who do imaging studies can map
-
6:17 - 6:20into our ultimate database,
an Atlas framework. -
6:20 - 6:23We also collect diffusion tensor images,
-
6:23 - 6:25so we get some of the wiring
from these brains. -
6:25 - 6:28And then the brain
is removed from the skull. -
6:28 - 6:33It's slabbed and frozen solid,
and then it's shipped to Seattle -
6:33 - 6:35where we have
the Allen Institute for Brain Science. -
6:35 - 6:37We have great technicians
who've worked out -
6:37 - 6:39a lot of great techniques
for further processing. -
6:40 - 6:46So first, we take a very thin section,
this is a 25 micron thin section, -
6:46 - 6:48which is about a baby's hair width.
-
6:48 - 6:52That's transferred to a microscope slide
and then that is stained -
6:52 - 6:56with one of those histological stains
that I talked about before. -
6:56 - 6:59And this is going to give us more contrast
as our team of anatomists -
6:59 - 7:03start to make assignments of anatomy.
-
7:05 - 7:07So we digitize these images,
-
7:07 - 7:11everything goes from being
wet lab to being dry lab. -
7:11 - 7:16And then combined with anatomy
that we get from the MR, -
7:16 - 7:18we further fragment the brain.
-
7:18 - 7:24This is to get it into a smaller framework
for which we can do this. -
7:24 - 7:27So here's a technician
who's doing additional cutting. -
7:27 - 7:30This is again a 25 micron thin section.
-
7:30 - 7:33You'll see da Vinci's tools,
the paintbrush, -
7:33 - 7:35being used here to smooth this out.
-
7:35 - 7:39This is fresh frozen brain tissue.
-
7:39 - 7:43And it can be very carefully
melted to a microscope slide. -
7:43 - 7:45You'll note that there's a barcode
on the slide. -
7:45 - 7:47We process 1000's and 1000's of samples,
-
7:47 - 7:51we track all of it in a backend
information management system. -
7:51 - 7:54Those are stained.
-
7:54 - 7:57And then we get
more detailed anatomic information. -
7:57 - 7:58That information...
-
8:02 - 8:08This is a laser capture microscope.
-
8:08 - 8:13The lab technician is actually describing
an area on that slide. -
8:13 - 8:15And a laser, you see the blue light
cutting around there, -
8:15 - 8:19very James Bond-like,
cutting out part of that. -
8:19 - 8:22And underneath there,
you can see the blue light again, -
8:22 - 8:24from the microscope in real-time,
-
8:24 - 8:29it's collecting,
in a microscope tube, that tissue. -
8:29 - 8:31We extract RNA,
-
8:31 - 8:35RNA is the product of the genes
that are being turned on, -
8:35 - 8:38and we label it,
we put a fluorescent tag on it. -
8:38 - 8:40Now what you are looking at here
-
8:40 - 8:43is a constellation
of the entire human genome -
8:43 - 8:45spread out over a glass slide.
-
8:45 - 8:49Those little bits are representing
the 25,000 genes. -
8:49 - 8:53There's about 60,000 of these spots
and that fluorescently labeled RNA -
8:53 - 8:57is put onto this microscope slide
and then we read out quantitatively -
8:57 - 9:01what genes are turned on at what levels.
-
9:01 - 9:05So we do this over and over and over again
for brains that we've collected; -
9:05 - 9:07as I mentioned we've collected
6 brains in total. -
9:07 - 9:11We collect samples
from about 1000 structures in every brain -
9:11 - 9:15that we've looked at,
so it's a massive amount of data. -
9:15 - 9:19And we pull all of this together,
back into a common framework, -
9:19 - 9:23that is a free and open resource
for scientists around the world to use. -
9:23 - 9:25So at the Allen Institute
for Brain Science, -
9:25 - 9:29we've been generating these kinds
of data resources for almost a decade. -
9:29 - 9:32They're free to use for anybody,
they're online tools, -
9:32 - 9:38just for example today a given workday,
there'll be about 1000 unique visitors -
9:38 - 9:44that come in from labs around the world,
to come use our resources and data. -
9:44 - 9:48They get access to tools like this,
which allows them to see -
9:48 - 9:51all of that anatomy and the structure
that we created before -
9:51 - 9:56and to start mapping in then the things
that they're particularly interested in. -
9:56 - 9:58So in this case you're looking
at the structure -
9:58 - 10:00and they're going to look
at these color balls -
10:00 - 10:03are representing a particular gene
they're interested in -
10:03 - 10:05that's either being turned up or down
-
10:05 - 10:12in those various areas depending upon
the heat color that's specified there. -
10:12 - 10:15So what are people doing
when they start using these resources? -
10:15 - 10:17Well, one of the things
that you might hear lots about -
10:17 - 10:20is human genetic studies.
-
10:20 - 10:23Obviously, if you're very interested
in understanding disease -
10:23 - 10:26there's a genetic underpinning
to many of them. -
10:26 - 10:28So you'd like more information,
you do a large-scale study -
10:28 - 10:31and you get out of those studies
collections of genes -
10:31 - 10:35and one of the first things you're going
to want to know is more information. -
10:35 - 10:41Is there something I can learn
about the location of these genes -
10:41 - 10:44that gives me additional clues
as to their function, -
10:44 - 10:49ways in which I might intervene
in the disease process. -
10:49 - 10:52They're also very interested
in understanding human genetic diversity. -
10:52 - 10:55We've only looked at 6 brains,
-
10:55 - 10:59but, as we know,
every human is very unique. -
10:59 - 11:01We celebrate our differences;
-
11:01 - 11:05this is a snapshot of the great workforce
at the Allen Institute for Brain Science -
11:05 - 11:09who does all the great work
that I'm talking about today. -
11:09 - 11:15But remarkably when we look at this level
at the underlying data, -
11:15 - 11:20and this is a lot of data from
2 completely unrelated individuals, -
11:20 - 11:24there's a very high degree
of correlation, correspondence. -
11:24 - 11:27So this is looking at thousands
of different measurements -
11:27 - 11:30of gene expression across
many, many different areas of the brain; -
11:30 - 11:32and there's a very high degree
of correspondence. -
11:32 - 11:34This was very reassuring to us.
-
11:34 - 11:37First, because when you generate
data on this scale, -
11:37 - 11:39you want to make sure it's high quality,
-
11:39 - 11:41so reproducibility is obviously important,
-
11:41 - 11:44but it was also important
because we feel that it's given us -
11:44 - 11:47a great snapshot into the human brain.
-
11:47 - 11:51And the people using the data,
even with our low N, have confidence -
11:51 - 11:54that what they're seeing
has some relevance. -
11:54 - 11:58Now, not everything is correlated here,
you can see some outliers, -
11:58 - 12:01and, of course, those outliers
are going to be interesting -
12:01 - 12:03related to human differences.
-
12:03 - 12:05We did a study a couple of years ago,
-
12:05 - 12:09in which we tried to understand
a little better about those differences, -
12:09 - 12:12and looked at multiple individuals
and different gene products, -
12:12 - 12:16and what we find, as a tendency
and as a rule, -
12:16 - 12:20is that those differences tend to be
in very specific cell populations -
12:20 - 12:24or cell types, cell classes,
as I mentioned before. -
12:24 - 12:27So, this is an example
of 2 different genes that are turned on -
12:27 - 12:30in very specific layers of the neocortex
-
12:30 - 12:33only in one individual
and not found in another. -
12:33 - 12:36Now we have no idea
if that's due to environmental changes, -
12:36 - 12:39environmental influences
or if it's just genetics, -
12:39 - 12:43but we did do a study in which we looked
at the mouse several years ago -
12:43 - 12:48and we were looking at genes
that encode for, in this case a DRD2, -
12:48 - 12:52the gene listed on the top
is a dopamine receptor. -
12:52 - 12:59Tyrosine hydroxylase, TH, is a gene
involved in dopamine biosynthesis -
12:59 - 13:03and those 2 gene products
are very different in the cell types -
13:03 - 13:06in these individual mouse brains.
-
13:06 - 13:12So, over on the left is "C57 Black 6"
which is a commonly used mouse strain, -
13:12 - 13:15and then spread at the other end
is a wild type strain. -
13:15 - 13:20And so the further you go
the more genetically unrelated you are. -
13:20 - 13:24And when we looked in total across,
sort of evolution if you will, -
13:24 - 13:26across genetic relatedness,
-
13:26 - 13:28the further you were
genetically unrelated, -
13:28 - 13:30the more of these
very specific cell types, -
13:30 - 13:33specific changes, you could see.
-
13:34 - 13:36So at the Allen Institute
for the next decade -
13:36 - 13:39we're embarking
on a pretty ambitious program -
13:39 - 13:43to start to understand the cell types,
understand the cell differences -
13:43 - 13:47and how they ultimately relate
to the functional properties of the brain. -
13:47 - 13:51This is, I think, critical information
for the entire field, -
13:51 - 13:54to start linking up all
of these fundamental parts -
13:54 - 13:57which are the cells,
to how they're connected, -
13:57 - 14:01the underlying molecules
that drive those connections, -
14:01 - 14:04the underlying molecules driving
the electrophysiological properties, -
14:04 - 14:07the electrochemical properties
-
14:07 - 14:10and then ultimately
the functional properties of those cells. -
14:10 - 14:14So we're doing this
in 3 different areas of research. -
14:14 - 14:17First, we're focusing on the mouse,
the mouse visual system, -
14:17 - 14:21to look at, in real-time,
in the living animal, -
14:21 - 14:26the functions of a variety
of different cells. -
14:26 - 14:29We're linking these in this concept
in the middle of cell types, -
14:29 - 14:34trying to really understand
the underlying molecules -
14:34 - 14:37in all the properties
as they relate to those functions -
14:37 - 14:40and then we're looking at the human.
-
14:40 - 14:44In the human we're doing this both
in the middle and cell types -
14:44 - 14:47using the tissue driven work
that I talked about before, -
14:47 - 14:52but also we're doing it in vitro
using stem cell technology. -
14:52 - 14:55We're learning how to make
very specific cell types within the dish -
14:55 - 14:58and then being able to test
those functional properties -
14:58 - 15:05and go back and forth between
what we learn in the mouse to the human. -
15:05 - 15:09So, with that I will finish
and just say that it's an exciting time -
15:09 - 15:11to be in biology and an exciting time
to be in neuroscience. -
15:11 - 15:15I think the technology of the day
has come well beyond the pen and paper -
15:15 - 15:21and it's really time for a renaissance in
our understanding of this complex organ. -
15:21 - 15:22Thanks.
-
15:22 - 15:24(Applause)
- Title:
- A map of the brain: Allan Jones at TEDxCaltech
- Description:
-
The talk covers some of the more recent research going on in understanding the function of the brain.
- Video Language:
- English
- Team:
- closed TED
- Project:
- TEDxTalks
- Duration:
- 15:31
Ariana Bleau Lugo commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Robert Tucker commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Ariana Bleau Lugo commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Robert Tucker commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Krystian Aparta edited English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Madina Juarez commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Madina Juarez commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech | ||
Robert Tucker commented on English subtitles for A map of the brain: Allan Jones at TEDxCaltech |
Ariana Bleau Lugo
It's intimidating how perfect your work is, Robert :)
Krystian Aparta
Good job on the transcript. I fixed the reading speed of some subtitles where it went over 21 characters per second.
Madina Juarez
Per 1:10 - 1:13 which comes out
into your cervical spinal fluid.
Should be cerebral spinal fluid, not cervical spinal fluid.
Regards,
Madina Juarez
Madina Juarez
Per 3:20 - 3:23
and small support cells
that are glias and astrocytes
Should read glials (as in glial cells).
Madina Juarez
Per 4:57 - 4:59 and obviously it's useful => and obviously, as you saw it before
Per 14:01 - 14:04 the underlying molecules that drive the physiological properties, => the underlying molecules that drive the electrophysiological properties,
Robert Tucker
4:57 - 4:59 and 14:01 - 14:04 Yes, you're right. Thank you. Hopefully, someone can correct it.
1:10 - 1:13 I think he actually says cervical spinal fluid. I think he could equally have said cerebrospinal fluid (CSF) but cervical here relates to the neck region of the spine, not a part of female anatomy.
3:20 - 3:23 Glial cells, sometimes called neuroglia or simply glia (http://en.wikipedia.org/wiki/Neuroglia)
Madina Juarez
Robert, with all due respect, (1) there is no such thing as a "cervical spinal fluid". What Dr. Jones is referring to, and you can see it in the following subtitle line, is CSF. CSF is a part of central nervous system, and stands for cerebral spinal fluid, or cerebrospinal fluid (http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm). (2) As far as glia/neuroglia goes, it's a plural form, you are right. However, if you want to be linguistically accurate, you would either call it glia, or glials, not "glias" as you worded it (http://www.ncbi.nlm.nih.gov/books/NBK10869/). Regards, Madina
Madina Juarez
Yes, I also hope, these get corrected. :-) Thank you!
Robert Tucker
Yes, OK, thank you for the corrections Madina and Krystian. Apparently though "glias" is a valid Scrabble word and does better in English dictionaries than "glials". As for *no such thing* as "cervical spinal fluid" ... ?
Ariana Bleau Lugo
Robert, Madina is right about CSF. It's the fluid that fills the space between the arachnoid membrane and the pia mater, in both brain and spine, not just the cervical area. It's a well-known medical term.
Robert Tucker
Yes, I realize that Ariana. My last comment was just to point out that it also exists in the neck region. My error, my mishearing, may well have been my physicist brain thinking that things tend to drain downwards.
Ariana Bleau Lugo
While passing through C1-C7 vertebrae, CSF is not changing it's name. We are not yet Doctor Universalis to know it all, are we? I think we can settle for being exceptional without being perfect :)