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- [Narrator] We are the paradoxical ape.
Bipedal, naked, large brain.
Lone the master of fire, tools, and language,
but still trying to understand ourselves.
Aware that death is inevitable
yet filled with optimism.
We grow up slowly.
We hand down knowledge.
We empathize and deceive.
We shape the future from our shared understanding
of the past.
Carta brings together experts from diverse disciplines
to exchange insights on who we are
and how we got here.
An exploration made possible by the generosity
of humans like you.
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(applause)
- [Katerina] So, it's great to be here.
My colleague Jon Kass cannot be here today,
but he shared a few slides with me
and I'm going to share them with you.
It's the four first slides in my presentation.
Primate brains vary a lot in terms of overall size.
So we have here a couple of examples:
one is a human brain and one is a microcebus brain,
huge differences in absolute brain size.
What we know is that we can have mammalian brains
that have similar brain sizes as a whole,
but many large differences in terms
of the number of cells that they contain.
And here we have an example of an owl monkey to the left
and an agouti mammalian brain to the right.
Early mammals, Jon suggests,
may have had about 20 cortical areas
and this reconstruction is based on fossil records
and also in comparison with extant species.
What you have here up left is a drawing that represents
an early mammal and from fossils, of course,
we get information about shape, overall size,
and some patterns of convolutions.
Recently, imaging studies have reconstructed
a couple of brains in the context
of the number of cortical areas that they have.
So here we have an example of a macaque cortex
that is estimated to have about 140 areas,
according to this study.
While the human cortex, according to another study,
has probably around 183.
So the question that Jon poses is:
how many cortical areas do the rest
of the primate species have, including the great apes?
That's an answer that is not there in place yet.
What is fascinating in the line of research
of mammalian evolution is that things change
not by just increasing in overall size,
but also by actually subdividing and multiplying.
So what we have here is we have an example
of a squirrel mammal and a tree shrew.
That if you see to the right of the image,
the histological section,
it's clear that these two animals have single nucleus
that is a posterior pulvinar.
But if we look farther down to the Galago,
which is a prosimian,
a primate prosimian.
What we have is actually we have a split
of that same nucleus into two.
And a similar situation happens in other
anthropoid primates and so forth.
So the question is, how do we get these new areas?
What is the mechanism that brings these areas
and subdivisions about?
Jon wants to remind us that in primates we have eight,
not three or four, parietal frontal networks
like we have in other mammals.
So actions like looking, reaching, grasping,
body or head protection, aggressive face,
hand-to-mouth, running,
are really controlled by these neural networks
in the parietal and frontal lobe.
And the cortical areas that are involved in this networks
are actually multiple, they're not just one.
So he poses the questions,
how are these networks organized in humans
and do they differ between humans
and our closest relatives, the great apes?
So this is what brings us to my part of the lecture today.
How do we pursue human ape neuroanatomical comparisons?
So work on chimpanzees, gorillas, orangutans, gibbons,
and humans are for some of us,
and have been for pretty much everybody
for the last few decades, out of reach.
So the idea is study of the great apes and humans
involved only noninvasive techniques
and of course also brain tissue.
Right?
We need to have the brain tissue to be able to study
noninvasively the nervous system.
The techniques that exploded in the 60s and 70s
and later in the field of neurosciences
were very promising and very productive
in terms of experimental invasive studies
in animal models.
We learned a lot and we still learn a lot from that.
But what about the human ape comparisons?
So in the 90s,
the question of brain evolution
after the last common ancestor
was really out of reach.
But, if there is a will, there is a way.
So there was an obvious solution to that problem
and that was reaching out to zoos across the country
and asking for brain tissue that results
from natural deaths of the animals.
So that can be put together with human tissue
from the nations from the families of individuals who died.
So that early effort, collecting ape brain tissue
and then also applying those very,
very new noninvasive techniques
that started to become available for human studies.
The structure MRIs got applied to these postmortem scans
and the brains that were, back then, put in these buckets
and scanned in scanners meant to be for human scanning.
And then eventually that project gave rise
to living animals and living great apes.
And those early seeds of the work really moved
to an organized large-scale set of projects
that gave us a lot of studies,
literally hundred of studies, since the 90s
that involved structural imaging,
functional imaging of the great apes and humans
and also a lot of valuable tissue.
What have we learned?
So we have learned a lot of things
and it's daunting of a task to try to summarize,
but I want to bring up some, really quickly,
points that we learned that in some respects
humans scale or exhibit features just as expected
for a primate or an ape,
including the white matter and the corpus callosum size,
the gila to neuron rations,
the proportion of inhibitory GABAergic interneurons,
the size and neuron of the frontal lobe
and the frontal cortex.
Yes, the frontal cortex is three times larger in humans
but sure is the rest of the brain
when compared to the great apes.
We have macrostructural, microstructural,
and behavioral asymmetries that are widespread
and that they are not uniquely human,
as we used to think in the past.
Dendritic branching gets large in humans
but overall follows primate trends.
Axonal myelination also is expected for humans.
Humans not expected,
so we have reduction of the primary visual cortext,
increase of the temporal lobe.
We have increased size of neuropil space
and many other things.
And I want to focus on some of them in the time that I have.
So number and size of cortical areas,
well, how many do we have
and how do we differ from other primates?
Well, it depends on what we compare ourselves to.
So if we compare humans to macaques,
we have a picture up there to the left,
we have certain areas that are much,
much, larger in humans
but if we compare ourselves to the chimpanzees,
and the picture changes.
One area that seems to stand out is the frontal pole
of the prefrontal cortex and yes,
even though the frontal lobe has not
enlarged disproportionately in human evolution,
some cortical areas in that frontal lobe
actually have changed.
And the argument I want to make here with you today,
is sort of in line with what Evan and Dan
brought up earlier today,
the meeting in that those areas
that have changed in human evolution,
may seem to be more vulnerable to disorders,
including neurodevelopmental disorders.
The questions for the future are:
well, what happens to the other cortical areas
and how large are they?
We still have not had a chance to address that.
Density and number of neurons.
Evolution.
We have bigger brains have more neurons.
We have decrease in cell density
and there is a lot of variation
and that depends on where exactly we are in the brain.
It's not homogeneous.
In neurodevelopmental disorders,
interestingly, the prefrontal cortex
is one of the areas that seems to be extremely
vulnerable to disease.
And what I have here is an example
from a study on autism
and controls where we have an overproduction
of neurons in the prefrontal cortex
in autism
and we have also the prefrontal cortex
been affected in other disorders
like Williams Syndrome, for example.
Cortical minicolums.
So the density in the brain, in the cortex,
does not just vary homogeneously across cortical areas
but it's specific to where we are in the brain,
what layer we're in the brain, and so forth.
So early in development, in the cortex
what we have is the cells align in columns very closely,
cluster together, and as individual grows older,
those minicolumns tend to go farther apart.
If we compare monkeys to chimpanzees and to humans,
so very big difference in terms of size,
humans have the wider space between their minicolumns.
What we found is that actually
after the last common ancestor with the great apes,
this size of the minicolumns
again is very specific to where in the brain we look at,
and one of the areas that has changed the most
seems to be, again, the frontal pole.
So it is that area that has really
seen some dramatic changes in the course of evolution.
And on the right, you see an example
of minicolumns in autism and controls.
In autism, the minicolumns are actually collapsing.
We have many, many, more cells
than we have in controls.
Dendritic branching.
I did not pay Evan to introduce that for me
but that's what we see in the phenotype, in the brains.
Dendritic branching is very important
so this is how neurons communicate to each other.
They determine the number of spines
and then their connections that the cells have.
So what you have here in the big drawing on the left
is typical cortical neurons in layer three
in various parts of the cortex.
And it just so happens that areas
that have high degration, like area 10
and other parts of the prefrontal cortex,
tend to have larger branched neurons
than the lower integration areas in the cortex.
In the chimpanzees, we have a similar pattern
but the overall tree is smaller
across the brain.
Interestingly, neurodevelopmental disorders
exhibit a lot of problems in the way
that the cells branch and develop.
And what you have at the bottom here
is an example of how area ten
has been compromised in Williams Syndrome.
A fascinating story has to do with the amygdala.
So we think a lot about the cortex
when we talk about brain evolution,
but the reality is that everything in the brain
works in terms of systems and circuits.
So a very important finding replicated
by different lines of work and different laboratories,
has shown that the lateral nucleus of the amygdala
is actually much larger in humans than in great apes
and is also affected differentially in Williams Syndrome
and autism in exactly opposite directions.
Of course, that becomes even more interesting
when we think about the fact that temporal lobe in humans
is actually larger than expected
and like the frontal lobe,
temporal is larger than expected
and it just so happens that the lateral nucleus
is highly interconnected with the temporal lobe.
Of course, neural systems
it is very important to bring up
this very elegant line of work by Leah Krubitzer here
because nothing in evolution of humans and apes
in terms of the brain makes sense
outside the light of mammalian evolution.
And the example here shows you
a blind mole rat that still has visual cortex in its brain
and also, an entire neural system is still in place,
it has not really disappeared in this animal.
But guess what?
It has been co-opted by other senses
so it functions in a different way,
co-opted by the auditory system.
Now, experimental work in her lab
has shown that if you bilaterally enucleate
the normal opossum what you have is not only difference
in the cortical areas in that animal,
but also a substantial change
in how projections from the thalamus
go to the visual cortex.
So it's not only the cortex that changes,
it's also the subthalamic nuclei
and also the other nuclei,
whatever neural system we are thinking about.
So I'm gonna skip this slides in the interest of time
although we have very interesting findings
on this striatum and the mylination of axons.
The questions now becomes
how can we blend the work on animal models
with non-invasive studies on humans and the great apes?
What is homologous in terms of function?
Because that's really what matters, right?
What does it mean to have a structure in place
that no longer performs its evolutionary function
but is co-opted by another one?
How do we tell them apart in humans and apes?
We have this new line of work,
this new technology to induced pluripotent stem cells,
which is going to be discussion probably
the next 10 years celebration of Carta,
but this gives us the power to describe
and experiment on developmental differences
in humans and the great apes in the dish.
And I brought up a couple of examples
on control and Williams Syndrome
and then apes and humans
that show the power that putting together
classical neuroanatomy techniques
with these invasive experimental techniques in the dish
can give us.
So can we put the phenotype and the mechanism together?
That's a question for the future.
The way I envision the next 10 years of Carta
is putting together the information from the genome
to that of live neurons in the dish,
the tissue in the brains, the imaging,
and then put that together
with the bones and the fossil record
and of course, all of that,
in the context of the whole organism and the social context
because we are social primates after all.
And I would like to leave you with these three questions
that I think are very important.
Not specific to my field,
but are very important for our future.
We are faced today with unprecedented
technological advances.
Should our future be driven by technology
or by our questions?
What about the impact of our science?
Who will be in charge?
Who is responsible?
The STEM, so the sciences, engineering, technology,
needs to work together with social sciences
and the humanities.
And I think that this combination
is what makes Carta training unique
and that's the way of the future.
So thank you very much.
(applause)
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