A map of the brain: Allan Jones at TEDxCaltech
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0:01 - 0:02Complexity.
-
0:02 - 0:05Nothing quite embodies the word
like the human brain. -
0:05 - 0:10So for centuries we've studied
the complexity of the human brain -
0:10 - 0:13using the tools and technology of the day.
-
0:13 - 0:16If that's pen and paper
from the age of da Vinci -
0:16 - 0:18through advents in microscopy
-
0:18 - 0:21to be able to look more deeply
into the brain -
0:21 - 0:25to a lot of the new technologies
that you've heard about today -
0:25 - 0:28through imaging,
magnetic resonance imaging, -
0:28 - 0:31able to look a the details
of the brain. -
0:31 - 0:35Now one of the first things
you notice when you look -
0:35 - 0:38at a fresh human brain
is the amount of vasculatur -
0:38 - 0:40that's completely covering this.
-
0:40 - 0:44The brain is this metabolically
voracious organ. -
0:44 - 0:47Approximately a quarter of the oxygen
in your blood, -
0:47 - 0:51approximately a fifth of the glucose
in your blood -
0:51 - 0:53is being used by this organ.
-
0:53 - 0:57It's so metabolically active
there's a waste stream which comes out -
0:57 - 1:02into your cervical spinal fluid.
You generate 0.5 liter of CSF every day. -
1:02 - 1:06So, as you know, researchers
have taken advantage -
1:06 - 1:10of this massive amount of blood flow
and metabolic activity -
1:10 - 1:15to begin to map regions of the brain,
to functionally annotate the brain -
1:15 - 1:16in very meaningful ways.
-
1:16 - 1:20You'll hear a lot more
about those kinds of studies, -
1:20 - 1:25but basically taking advantage of the fact
that there's active metabolism -
1:25 - 1:27with certain tasks going on.
-
1:27 - 1:31You can put a living human in a machine
and you can see various areas -
1:31 - 1:33that are lighting up.
-
1:33 - 1:37For example, going around right now
is the temporal cortex auditory -
1:37 - 1:41processing going on there,
you're listening to my words, -
1:41 - 1:44you're processing what I'm saying.
-
1:44 - 1:48Moving to the front of this brain
is your prefontal cortex, -
1:48 - 1:50your executive decision-making,
-
1:50 - 1:53your higher-thinking areas
of the brain. -
1:53 - 1:56And so the thing that
we're very much interested in -
1:56 - 1:59from the perspective
of the Allen Institute -
1:59 - 2:03is to go deeper,
to get down to the cellular level. -
2:03 - 2:08So when you look at this slice, it doesn't
really look like gray matter, does it? -
2:08 - 2:11It's more tan matter, or beige matter.
-
2:11 - 2:14And scientists about, I guess,
around the late 1800's -
2:14 - 2:18discovered that they could stain tissue
in various ways, -
2:18 - 2:23and this sort of came along
with various microscopy techniques. -
2:23 - 2:27And so this is a stain, it's called Nissl,
and it stains cell bodies, -
2:27 - 2:30it stains the cell bodies purple.
-
2:30 - 2:33And so you can see
a lot more structure and texture -
2:33 - 2:36when you look at something like this.
-
2:36 - 2:40You can see the outer layers of the brain
and the neocortex, -
2:40 - 2:45there's a six-layer structure,
arguably what makes us most uniquely human. -
2:45 - 2:49As you've heard before about
there's on average in a human -
2:49 - 2:53there's about 86 billion neurons
and those 86 billion neurons -
2:53 - 2:59you can see are not evenly distributed,
they're very focused and specific structures. -
2:59 - 3:02And each of them
has their own specific function -
3:02 - 3:06both on an anatomic level
and at a cellular level. -
3:06 - 3:10So if we zoom in on these cells,
what you can see is large cells -
3:10 - 3:14and small support cells
that are glias and astrocytes -
3:14 - 3:19and these cells are as we know
connected in a variety of different ways. -
3:22 - 3:26And we like to think about
although there's 86 billion cells, -
3:26 - 3:31each cell might be considered a snowflake,
they're actually able to be binned -
3:31 - 3:34into a large number
of cell types or classes. -
3:34 - 3:38What flavor of activity
that particular cell class has -
3:38 - 3:42is driven by the underlying genes
that are turned on in that cell, -
3:42 - 3:47those drive protein expression
which guide the function of those cells, -
3:47 - 3:51who they're connected to,
what their morphology is -
3:51 - 3:55and we're very much interested
in understanding these cell classes. -
3:55 - 3:57So how do we do that?
-
3:57 - 4:00Well, we look inside the cell
at the nucleus, -
4:00 - 4:02and it will get to the nucleus,
-
4:02 - 4:05and so inside we've got
23 pairs of chromosomes, -
4:05 - 4:08we've got a pair from mom,
a pair from dad, -
4:11 - 4:17on those chromosomes about 25000 genes
and we're very much again interested in -
4:17 - 4:19understanding which of these 25000 genes
-
4:19 - 4:23are turned on and
at what levels they're turned on. -
4:23 - 4:28Those are going of course to 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 - 4:39what the driving biochemistry
driven by our genome is. -
4:39 - 4:41So how do we do that?
-
4:41 - 4:44We're going to deconstruct a brain
in several easy steps. -
4:44 - 4:47So we start at a medical examiner's office.
-
4:47 - 4:51This is a place
where the dead are brought in -
4:51 - 4:52and obviously it's useful,
-
4:52 - 4:56for the kind of work we do
is not non-invasive, -
4:56 - 4:59we actually need
to obtain fresh brain tissue -
4:59 - 5:04and we need to obtain it within 24 hours
because the tissues start to degrade. -
5:04 - 5:06We also wanted for our projects304306.1
-
5:06 - 5:10to have normal tissue
as much normal as we could possibly get. -
5:10 - 5:15So over the course of a two-
or three-year collection time window -
5:15 - 5:20we collected 6 very high-quality brains,
5 of them were male, one was female, -
5:20 - 5:24That's only because males
tend to die untimely deaths -
5:24 - 5:28more frequently than females
and then to add to that females -
5:28 - 5:33are much more likely to give consent
for us to take the brain than vice versa. -
5:33 - 5:35We have to figure that one out.
-
5:35 - 5:39We've heard people say,
“He wasn't using it anyway!” -
5:39 - 5:43So, once the brain comes in
we have to move very, very quickly. -
5:43 - 5:47So first we capture
a magnetic resonance image. -
5:47 - 5:50This, of course,
will look very familiar to you, -
5:50 - 5:55but this is going to be the structure
in which we hang all of this information, -
5:55 - 6:00it's also a common coordinate framework
by which the many, many researchers -
6:00 - 6:02who do imaging studies can map
-
6:02 - 6:06into our ultimate database,
an Atlas framework. -
6:06 - 6:08We also collect diffusion tensor images
-
6:08 - 6:12so we get some of the wiring
from these brains -
6:12 - 6:16and then the brain is removed
from the skull. It's slabbed and frozen, -
6:16 - 6:20frozen solid,
and then it's shipped to Seattle -
6:20 - 6:23where we have
the Allen Institute for Brain Science. -
6:23 - 6:26We have great technicians
who've worked out -
6:26 - 6:29a lot of great techniques
for further processing. -
6:29 - 6:34So first, we take a very thin section,
this is 25µm thin section, -
6:34 - 6:36which is about a baby's hair width.
-
6:36 - 6:41That's transferred to a microscope slide
and then that is stained -
6:41 - 6:45with one of those histological stains
that I talked about before. -
6:45 - 6:50And this is going to give us more contrast
as our team of anatomists -
6:50 - 6:52start to make assignments of anatomy.
-
6:52 - 6:54So we digitize these images,
-
6:54 - 6:58everything goes from being wet lab
to being dry lab. -
6:58 - 7:04And then combined with anatomy that we get
from the MR we further fragment the brain. -
7:04 - 7:08This is to get it into a smaller framework
for which we can do this. -
7:08 - 7:12So here's a technician
who's doing additional cutting. -
7:12 - 7:14This is again a 25µm thin section.
-
7:14 - 7:20You'll see da Vinci's tools, the paintbrush,
being use here to smooth this out. -
7:20 - 7:22This is fresh frozen brain tissue.
-
7:22 - 7:26And it can be very carefully
melted to a microscope slide. -
7:26 - 7:29You'll note
that there's a barcode on the slide. -
7:29 - 7:32We process 1000's and 1000's of samples,
-
7:32 - 7:36we track all of it
in a backend information management system. -
7:36 - 7:38Those are stained.
-
7:38 - 7:41And then we get
more detailed anatomic information. -
7:41 - 7:46That information is, playing here,
this is a laser capture microscope, -
7:46 - 7:50the lab technician is actually describing
an area on that slide. -
7:50 - 7:54And a laser,
you see the blue light cutting around there, -
7:54 - 7:56very James Bond like.
-
7:56 - 7:59Cutting out part of that,
and underneath there, -
7:59 - 8:04you can see the blue light again,
from the microscope in real-time. -
8:04 - 8:07It's collecting in a microscope tube that tissue.
-
8:07 - 8:08We extract RNA,
-
8:08 - 8:12RNA is the product of the genes
that are being turned on, -
8:12 - 8:15and we label it,
we put a fluorescent tag on it. -
8:15 - 8:21Now what you are looking at here
is a constellation of the entire human genome -
8:21 - 8:23spread out over a glass slide.
-
8:23 - 8:26Those little bits are representing
the 25000 genes. -
8:26 - 8:31There's about 60000 of these spots
and that fluorescently labeled RNA -
8:31 - 8:36is put onto this microscope slide
and then we read out quantitatively -
8:36 - 8:38what genes are turned on at what levels.
-
8:38 - 8:44So we do this over and over and over again
for brains that we've collected. -
8:44 - 8:47As I mentioned we've collected
6 brains in total. -
8:47 - 8:51We collect samples
from about 1000 structures in every brain -
8:51 - 8:55that we've looked at,
so it's a massive amount of data. -
8:55 - 8:59And we pull all of this together,
back into a common framework, -
8:59 - 9:04that is a free and open resource
for scientists around the world to use. -
9:04 - 9:09So at the Allen Institute for Brain Science,
we've been generating -
9:09 - 9:12these kinds of data resources
for almost a decade. -
9:12 - 9:16They're free to use for anybody,
they're online tools, -
9:16 - 9:21just for example today a given workday,
there'll be about 1000 unique visitors -
9:21 - 9:26that come in from labs around the world
to come use our resources and data. -
9:26 - 9:30They get access to tools like this,
which allows them -
9:30 - 9:34to see all that anatomy
and the structure that we created before -
9:34 - 9:40and to start mapping in then the things
that they're particularly interested in. -
9:40 - 9:43So in this case you're looking
at the structure -
9:43 - 9:46and they're going to look
at these color balls -
9:46 - 9:49are representing a particular gene
-
9:49 - 9:53they're interested in that's
either being turned up or down -
9:53 - 9:58in those various areas depending
on the heat color that's specified there. -
9:58 - 10:02So what are people doing when they come in
and using these resources? -
10:02 - 10:06Well, one of the things
that you might hear lots about -
10:06 - 10:08is human genetic studies.
-
10:08 - 10:12Obviously if you're very interested
in understanding disease -
10:12 - 10:15there's a genetic underpinning
to many of them. -
10:15 - 10:17So you'd like more information,
-
10:17 - 10:21you do a large-scale study
and you get out of those studies -
10:21 - 10:25collections of genes
and one of the first things -
10:25 - 10:28you're going to want to know
is more information. -
10:28 - 10:33Is there something I can learn
about the location of these genes -
10:33 - 10:36that gives me additional clues
as to their function, -
10:36 - 10:40ways in which I might intervene
in the disease process. -
10:40 - 10:45They're also very interested
in understanding human genetic diversity. -
10:45 - 10:50Now we've already looked at 6 brains
but as we know, every human is very unique. -
10:50 - 10:52We celebrate our differences;
-
10:52 - 10:58this is a snapshot of the great workforce
at the Allen Institute for Brain Science -
10:58 - 11:02who does all the great work
that I'm talking about today. -
11:02 - 11:06But remarkably when we look at this level
at the underlying data -
11:06 - 11:11and this is a lot of data from 2 completely
unrelated individuals -
11:11 - 11:15there's a very high degree
of correlation, correspondence. -
11:15 - 11:20So this is looking at 1000's
of different measurements of gene expressions -
11:20 - 11:23across many, many different
areas of the brain. -
11:23 - 11:26And there's
a very high degree of correspondence. -
11:26 - 11:28This was very reassuring to us.
-
11:28 - 11:32First because when you generate data
on this scale -
11:32 - 11:38you want to make sure that it's high quality,
so reproducibility is obviously important, -
11:38 - 11:42but it was also important
because we feel that it's given us -
11:42 - 11:45a great snapshot into the human brain.
-
11:45 - 11:49And the people using the data,
even with our low n have confidence -
11:49 - 11:52that what they're seeing has some relevance.
-
11:52 - 11:57Now not everything is correlated here,
you can see some outliers, -
11:57 - 12:00and of course those outliers
are going to be interesting -
12:00 - 12:02related to human differences.
-
12:02 - 12:05We did study a couple of years ago
-
12:05 - 12:10in which we tried to understand
a little better about those differences -
12:10 - 12:14and looked at multiple individuals
and different gene products -
12:14 - 12:19and what we find is that a tendency
and as a rule is that those differences -
12:19 - 12:23tend to be in very specific
cell populations or cell types, -
12:23 - 12:25cell classes as I mentioned before.
-
12:25 - 12:30So, this is an example
of 2 different genes that are turned on -
12:30 - 12:34in a very specific layers
of the neocortex only in one individual -
12:34 - 12:36nd not found in another.
-
12:36 - 12:40Now we have no idea
if that's due to environmental changes, -
12:40 - 12:43environmental influences
or if it's just genetics. -
12:43 - 12:48But we did do a study in which we looked
at the mouse several years ago -
12:48 - 12:53and we were looking at genes
that encode for, in this case a DRD2, -
12:53 - 12:56the gene listed on the top
is a dopamine receptor. -
12:56 - 13:01Tyrosine hydroxylase (TH)
is a gene involved in dopamine biosynthesis -
13:01 - 13:05and those 2 gene products
are very different in the cell types -
13:05 - 13:08in these individual mouse brains.
-
13:08 - 13:13So, over on the left is “C57 black 6”
which is a commonly used mouse strain, -
13:13 - 13:17and then spread at the other end
is a wild type strain. -
13:17 - 13:21And so the further you go
the more genetically unrelated you are. -
13:21 - 13:26And when we looked in total across,
sort of evolution if you will, -
13:26 - 13:30across genetic relatedness,
the further you were genetically unrelated, -
13:30 - 13:33the more of these very specific cell types,
-
13:33 - 13:36specific changes, you could see.
-
13:36 - 13:39So at the Allen Institute
for the next decade -
13:39 - 13:42we're embarking
on a pretty ambitious program -
13:42 - 13:47to start to understand the cell types,
understand the cell differences -
13:47 - 13:52and how they ultimately relate
to the functional properties of the brain. -
13:52 - 13:56This is, I think, critical information
for the entire field, -
13:56 - 14:00to start linking up all
of these fundamental parts which are cells, -
14:00 - 14:02to how they're connected,
-
14:02 - 14:06the underlying molecules
that drive those connections, -
14:06 - 14:10the underlying molecules
that drive the physiological properties, -
14:10 - 14:14the electric chemical properties
and then ultimately -
14:14 - 14:17the functional properties of those cells.
-
14:17 - 14:20So we're doing this
in 3 different areas of research. -
14:20 - 14:24First we're focusing on the mouse,
the mouse visual system, -
14:24 - 14:27to look at, in real-time,
in the living animal -
14:27 - 14:31the functions of a variety
of different cells. -
14:31 - 14:35We're linking these in this concept
in the middle of cell types, -
14:35 - 14:38trying really understand
the underlying molecules -
14:38 - 14:42in all the properties
as they relate to those functions -
14:42 - 14:45and then we're looking at the human.
-
14:45 - 14:49In the human we're doing this both
in the middle and cell types -
14:49 - 14:53using the tissue driven work
that I talked about before -
14:53 - 14:57but also we're doing it in vitro
using stem cell technology. -
14:57 - 15:01We're learning
how to make very specific cell types -
15:01 - 15:03within the dish
and then being able to test -
15:03 - 15:07those functional properties
and go back and forth -
15:07 - 15:10between what we learn in the mouse
to the human. -
15:10 - 15:15So, with that I will finish
and just say that it's an exciting time -
15:15 - 15:16to be in biology
-
15:16 - 15:19and an exciting time
to be in neuroscience. -
15:19 - 15:24I think the technology of the day
has come well beyond the pen and paper -
15:24 - 15:29and it's really time for a renaissance in
our understanding of this complex organ. -
15:29 - 15:30Thanks.
- Title:
- A map of the brain: Allan Jones at TEDxCaltech
- Description:
-
Allan Jones joined the Allen Institute in 2003 to help start up the organization as one of its first employees. Bringing extensive expertise in project leadership and high-throughput genomics operations from prior management positions at Merck and Co., Rosetta Inpharmatics and Avitech Diagnostics, Allan was instrumental in recruiting an integrated interdisciplinary team, building the Institute's scientific operations from the ground up and successfully driving the Allen Mouse Brain Atlas to completion in 2006. He provided strategic leadership and vision through the expansion of the Institute's portfolio of large-scale, high-impact initiatives from the mouse brain atlas through to work on the human brain. Allan has broad scientific experience in genetics, molecular biology and development. He holds a B.S. degree in biology from Duke University and a Ph.D. in genetics and developmental biology from Washington University School of Medicine in St. Louis.
In the spirit of ideas worth spreading, TEDx is a program of local, self-organized events that bring people together to share a TED-like experience. At a TEDx event, TEDTalks video and live speakers combine to spark deep discussion and connection in a small group. These local, self-organized events are branded TEDx, where x = independently organized TED event. The TED Conference provides general guidance for the TEDx program, but individual TEDx events are self-organized.* (*Subject to certain rules and regulations)
On January 18, 2013, Caltech hosted TEDxCaltech: The Brain, a forward-looking celebration of humankind's quest to understand the brain, by exploring the past, present and future of neuroscience. Visit TEDxCaltech.com for more details.
- 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 :)