Come on. Okay. So we're going to talk about serotonin.
Serotonin is kind of an underrated unknown role
maybe even through pregnancy. People often know
about serotonin later in life as a neuromodulator
for being responsible for things like mood and
appreciating and liking what you have type of
things like that but It does a lot more. It does,
um, especially in this timeframe here through
the different trimesters and through, we'll basically
get up to the, like the critical period here,
but we'll start with neuralation because we'll
have to, because we're developing the living
organism. One thing to know about serotonin is,
um, it comes from tryptophan, which is an aromatic
amino acid. The human body has 20 amino acids
and You can see these broken down into different
kind of subtypes. The aromatic type, tryptophan,
tyrosine, and phenylalanine are very diverse.
Tryptophan is similar to methionine because it
only has one codon. They're building block proteins.
So it makes sense that this building block protein
will be responsible for developing the living
organism. from the get go. Dr. Hannah Stevens
from the University of Iowa. She is an MD, PhD.
She studies kind of this timeframe. She's also
a clinical doctor and she's a neuroscientist.
What led me to her is the dorsal striatum because
of the basal ganglia. We have a lot of episodes
on the basal ganglia, but she studies this timeframe.
And you know, she's just fantastic. She has such
fantastic roles and research with autism. So
basically, what we're going to mainly talk about
is developing the sensory map. That's our end
goal. We're going to talk about the somatosensory
cortex, which is right about here, the visual
cortex, and then audition the auditory cortex
v1 and x1 are not as dominant here with the serotonin's
role as s1 map but let's get there the first
trimester remember this is uh remember the episodes
about neuralation just real quick here also about
tryptophan is there's two different distinct
pathways of tryptophan and At this time frame,
that's not so much the case because the fetus
has nothing. It's just helping develop. So, T
synthesizes tryptophan in the peripheral and
enteric nervous system. Tryptophan hydroxylase
-1. Remember, anytime you hear ACE or C -ACE,
A -S -C, it's an enzyme. Then the brain is T
-P -H -2. These don't cross over. in the developing
organism. But at this time, now this is kind
of drawn out and developed, but we're in the
first trimester here, before neurolation and
everything. Serotonin and tryptophan's role here
is just kind of providing neurogenesis and later
on a little bit of synaptogenesis because remember
the The neuralation. Remember we have neuroepithelial
cells. There's four of them that make the central
nervous system. And that's what we're gonna have
to talk about here. But we're gonna get there.
Remember the four neuroepithelial cells. Proencephalon.
Proencephalon, no, mesencephalon. mesencephalon
the one that doesn't subdivide and then the rhombencephalon
and then this will later develop this will later
subdivide into telencephalon for the cortex showing
up not bad diencephalon for the subcortical areas
and the eyes will extend out from the diencephalon
the mesencephalon here in the midbrain remember
from yeah we have a lot of episodes about the
mesencephalon because it doesn't subdivide and
it has three main roles that is trying to achieve
one is sensory integration two is motor movements
and three is kind of orienting the attention
of the living organism to the outside world so
that is why The mesencephalon is very fascinating
to me because all three of those are autism.
And then the ROM encephalon subdivides into the
MET and the MY encephalon. So things like the
pons cerebellum and then the MY encephalon for
the medulla and then the spine. Why this is going
to be important here is because where serotonin
is later made in the brain remember because it
doesn't cross over it's going to be important
here right here with the brain stem but we have
to first develop it let's see what else is important
here we've talked about things like sonic hedgehog
and p10 and then this phosphorus phosphorus and
with the mTOR rapamycin and then this right here
is like kind of a metabolic regulator of it and
sonic hedgehog and things because we're developing
the cells we have there's massive amounts of
cells dividing here and they're just explotential
there's so many cells happening serotonin is
kind of regulating that So we're getting to Neuralation
here not much is happening here as far as Developing
the organs and so forth the tissues of the brain
the central nervous system But okay, so Yeah,
the fetus here. Let's just touch on this real
fast because I think we'll just draw this out
about the sources of the serotonin the first
trimester this neurolation obviously there's
nothing there that the baby can make the fetus
can make so it gets all of it from the maternal
maternal tph1 the peripheral and her enteric
people would be maybe shocked to know that 95
or so of our serotonin is in the gut so the gut
serotonin tryptophan of the maternal here is
vastly important because now she has to supply
materials kind of building block materials here
for the placenta the umbilical cord and then
to the fetus remember what um the tryptophan's
role here with the placenta is if we were going
to we're not really subordinating or breaking
these out but As far as the molecule building
block for the placenta, tryptophan might be number
one. Remember, it's a building block with that
one codon and methionine. So it's vastly important
to hear the maternal's tryptophan and serotonin
levels. It's very delicate because of the roles
with the neurogenesis and so forth. So all of
it from the first trimester, it's coming from
the maternal nothing from the fetus it can't
we just drew out what looks like little peas
nothing's happening then however we get to the
second trimester and things start to kind of
shape all these tissues and brain regions what
we're going to get to begin taking shape okay
so something that we've talked a lot about is
the many columns because that's what it's going
to make these sensory maps or the many columns
again and the thalamus we talked a lot about
the thalamus remember it's a sensory relay station
and it's vastly important here and the serotonin
and the sensory map is that tissue the thalamus
and these sensory cortexes s1 v1 and a1 but remember
more s1 So serotonin's role here, let's just
draw this out. Let's just draw this out in a
way that kind of makes sense to us. Something
that we've seen before in the other videos, the
thalamus. Yeah, so we have the medial geniculate
right here, the relay station for audition, the
lateral geniculate, the relay station for vision.
And then the rest of the tissue that makes up
the thalamus. Okay. Remember it has the shell
over it too. That's going to be involved here.
But we're going to kind of go before that shell
somewhat. So let's just think about this as a
thalamus. This is the view from like overhead
and from the back because these are in the posterior
and inferior parts. Remember The midbrain is
just below here. And these things can just reach
out and high five each other because of they're
organizing for fast. First order sensory processing.
That's the whole thing we're talking about. So
the second trimester and so forth, these things
began taking shape. They're being structured.
And serotonin here is kind of regulating the
building block of this. So the fetus will begin
supplying its own, remember, because all of the
cell dividing and we've now mapped out the central
nervous system with that neurolation. So the
second trimester, the fetus begins to making
its own and it's kind of helping regulate the
nutrients and so forth, the physiology of the
umbilical cord, and then the placenta. If I didn't
mention, I don't remember if I did or not, but
remember the episode where Dr. Eric Weiss, he's
a surgeon, I believe an orthopedic surgeon, and
he's now shifting his role as an MD to more stem
cell research. umbilical cord stem cells to treat
autism. And he did it on his son, Marston. You
can see their story. I'm not pushing it, but
he happened to kind of naturally get into the
stem cell research because of his, he went to
Duke School of Medicine and they do some of that
stuff there. And at his residencies, he met other
doctors and research programs that do this for
other conditions. He's like, well, why not do
it for autism? He done it with his son Marston.
You can see their story but anyway the second
trimester The fetus in orange begins to make
more Maternals is still going to be pretty high
though, but not as much. It's not as required
So if this is the thalamus we have to get to
the cortex especially S1. Now, I'm not so sure
how we're gonna map this out, to be honest. Because
I really want to, I think I'll draw a lateral
view of it too. Something that we've, we know
is, you got the eyes and then the thalamus here,
basically in the middle, deep inside. And then
we have things like the brain stem, Cerebellum.
And the occipital. Up to the parietal. The sensory
motor area, which is where we're gonna spend
a lot of time. Getting up into the prefrontal
cortex. And then just to make sense of where
we are, the temporal lobe. so we're kind of looking
like this okay and then if we just want to kind
of make sense of the s1 area and also m1 because
we're going to kind of map out the homunculus
the homunculus is going to be mentioned and we're
going to I think maybe I'll draw it out. So S1
is back through here. Kind of slanted. So somatosensory
1 is like right there. And then the motor cortex
M1 is just in front of it. Remember this area
right here is sensory motor. Remember we have
the frontal eye fields up here and there's the
supplemental motor area SMA up here. All of our
reflexes and habits kind of go here. Remember
it conserves energy and the brain number one
goal is to conserve and allocate energy. Based
off of the sensations coming in it's going to
determine what do I need to activate and inactivate
while conserving energy. That's why habits are
So powerful So at this second trimester So this
is the thalamus here and we're going to start
building up cells and connections because serotonin
is main role here is the connections the so -called
wiring that Will provide these things to communicate
remember these are kind of distal areas here
So these distal connections things like white
matter tracks and so forth are important. Remember
the many columns too. So let's just draw out
some of the many columns because we're going
to talk about the differences between a properly
structured many column and remember the neuro
feel. So let's just get into this. Remember these
are layers of the cortex. We have six layers
in the cortex. They basically stack upon each
other like this, like crepes. They're basically
just like six crepes stacked together. We're
going to talk about two that we've already talked
a lot about. So this is good that we have this
background information and videos about this.
Remember, let me draw this out here. So let's
look at this mini column here, okay? So we have
a mini column here, and then we have another
mini column here. Remember, as we build mini
columns, they're macro columns. Then we have
this space in between, not Dave Matthews, but
this kind of space in between here is called
neurofeel. Okay, remember, with the autistic
phenotype, these are smaller roughly 40 50 60
microns versus a typical just 80 to 90 100 microns
or so so the difference of a thickness of the
sheet of paper is about 90 to 100 microns the
autistic phenotypes is half a thickness of a
sheet of paper we're going to get to why serotonin
is important for this creation and some of the
regions of the thalamus But first to recap we've
already talked about it probably a lot this Connections
come from the thalamus and enter layer 4 This
is called Thalamocortex This is thalamocortex
thalamus to the cortex landing spot is L4 layer
4 Layer 2 and 3 we'll get next right we've talked
about this so i won't spend a whole lot of time
here because that's where our experiences and
our intelligence everything we know our skill
sets and everything live kind of layer two and
three so sensory information is coming up then
recruits l two three four kind of what do i do
and then they're sending instructions back down
Two layer five and six, four. A big layer about,
I should just say it then, I guess. Five and
six have two different kind of layers. Five A,
five B, six A, six B. The one with six is speaking
back down to the thalamus. So corticothalamic.
Right, we've talked about this, but I think we're
gonna have to map this out so that we know Remember
below six is a bunch of white matter tracks.
Okay, so the second trimester and and beyond
serotonin is kind of providing wire diagrams
because these connections must communicate and
the way that they communicate or things like
axons and these so -called connections and so
forth so what is happening at this second trimester
because there's not a lot of sensory input for
the child and so forth it's just kind of building
these structures here just putting them in the
right place remember the differences between
proliferation differentiation and migration so
the second trimester here is a lot of neurogenesis
and then migration serotonin is responsible for
the areas of the thalamus in this s1 the relay
stations like for sensory v1 back here a1 up
here so it's very important that these things
are being built it's almost like i like st peter's
basilica i won't rant but i like st peter's basilica
and Serotonin here is like Michelangelo or Bernini.
It's like the architecture. It's determining
what goes where. So whenever this is kind of
abnormal, things start to become complicated
already. And this is very, this is, this is challenging.
This is because we're going to talk a lot about
the sensory overload and just it's chaotic and
so forth. There's a thing called diffusion. and
at this time point right here whenever these
things are being built and these connections
are being made as we're heading especially into
the third trimester there's a little crossover
here about how much the sources are from where
so the child will start to kind of supply its
own because it's you know it's getting bigger
and bigger What we're doing here is building
this foundation to get us towards perinatal birth
and the critical period. There's a lot of sensory
integration and processing, a lot of physical
phenomena just smothering these sensory processes.
So at this point though, there's a thing called
diffusion and then refinement. serotonin kind
of is modulating this so we can do this on the
seesaw because that's a good thing it's always
good to see things like this so diffusion refinement
when serotonin is off either high or low at this
point because of this tph1 tph2 type thing and
remember that the living organism, the fetus,
is developing its own so we've definitely developed
the central nervous system now. Serotonin for
the brain is made in right here in the brain
stem the mesencephalon and down into kind of
the pons area mostly the posterior side of the
mesencephalon remember we drew this out we kind
of drew this out the mesencephalon if we would
just splice the brain stem and kind of look at
the top of it because that's how you have to
look at the brain stem and spine we have this
para -aqueductal gray it's kind of like right
here and then serotonin So we can move vertically,
or if we're just looking at it overhead, it's
basically like right through here. And then it
will just come up and just sprinkle the brain,
essentially. There's a lot of connections. Serotonin
has a lot of receptors versus the other neuromodulators.
We haven't quite crossed over into the neuromodulator
yet. So it's still a building block. the third
trimester and then like perinatal there's a big
shift here because of growth is one and being
able to prepare the living organism the child
to receive the actual physical phenomena of sensation
sensation perception and whenever the serotonin
is bad remember the snorifil When serotonin is
bad, this neurofil will be smaller and there's
no real good edges anymore. So there's just a
lot going on here. Serotonin's role here is to
determine what is important versus what is not.
What stays versus what is pruned out. So these
connections remember we drew we extracted a specific
cell when we talked about OCD and the basal ganglia
a specific cell here If we just draw out a specific
cell however, we want it to look like it doesn't
It's not that important here, but then if we
zoom in this is zoom into here And we have these
spines here. Every time this spine receives a
connection, it will mean essentially the same
thing. This spine right here doesn't receive
different connections with different meanings.
So whenever these things are not pruned, there's
a lot of confusion. There's a lot of mismatched
and a lack of direction, a lack of kind of clear
-cut structure here of how to process sensations.
And that is diffusion. Diffusion doesn't have
clear edges with these many columns, which is
why the neurofil is smaller. Serotonin here has
to stamp, has to say, cut these connections out.
versus refinement. Refinement has clear -cut
edges. They have clear connections. They don't
have any competing kind of sensations and processes
to determine what should I pay attention to.
Diffusion is a lot of different weak connections
because the more connections you have, the more
competition there is. So there is very poor spatial
boundaries and remember we've also drew throughout
the signal to noise What are you going to pay
attention to? What is signal to pay attention
to versus what is noise? so In the autistic phenotype
a lot of time it looks like this to the environment
Not inside. Inside the living organism, inside
the autistic, it's different. There's a lot of
signal inward. Autism means self. Now this could
be very much a reason why because the outside
world is chaotic. So whenever you think about
this sensory processing. Just to finish up, so
we have the S1, we don't need little guy anymore,
so we have S1 somatosensory, which is processed
here, this connection right here. These mini
columns are essentially, could be, they're they're
pretty plug and play if you will except for there's
a little bit of different changes especially
with layer four with the mini columns so this
one for s1 or the v1 the a1 which is up here
but laterally very lateral and then visual cortex
back through here obviously in the occipital
lobe tomato sensory there's a VP and VL row here
little brain region that's responsible for speaking
up to the S1 because remember each connection
means the same thing and then V1 and A1 are Serotonin
here is involved in here very much with kind
of mapping out this diagram, but not as much
as S1 So this is huge here. So if we look at
S1 and we look at the so -called homunculus,
you've probably have seen it. Now I have to reverse
it. It's going to be complicated. It's not bad.
It's not bad. So if we just splice this out,
if we just splice this out and then just looked
at it like this, and you can see these all over
the internet. They're actually not bad. And then
for the sensory motor area here, you can see
it like side by side. So S1, what color we got?
Blue. And then S1 will receive the information
about the sensation, place, space and time, spatial
awareness and things like that. And then right
next to it is M1, because remember this other
layer six cortex is cortico -cortex, cortico
-cortex. So it's speaking across the cortex.
We receive information about the environment,
the space, and then we can have these motor movements
right here. So M1 will help modulate and control
motor movements. Each one of these sections,
this is what I'm getting to, each one of these
sections right here is responsible for different
areas of the body. Same for the somatosensory.
You can see great pictures of these. These are
basic pictures here. So whenever the sensory
map is abnormal and there are many different
connections and so forth, The autistic phenotype
will receive a lot of information here and not
know what to do with it. It cannot determine
signal to noise because there's no refinement.
Remember, refinement is like manicured yard.
People love doing yard work. Refinement is like
that. They have nice edges on their bushes and
nice landscaping and so forth. Diffusion is like
ivy. If you've ever had ivy, it just grows massively.
and it's just everywhere. That's diffusion. So
as we're getting to perinatal and birth, obviously
there's nothing from the maternal anymore because
they are separated. We're building up now to
the critical period and there is a lot of massive
sensations going on. So a fascinating question
about autism is of course how it's built but
is there something to do with the critical period
that makes it just a learned kind of characteristic,
a learned phenotype, a learned trait to stay
inward at this moment? Is there something to
do with early intervention before the critical
period? That's why I talk about the things like
the UCLA paper on the salience network. The salience
network is how do you modulate your attention?
And that's why that paper from 2024 UCLA that
found abnormal connections with the autistic
phenotype at six weeks old ought to be followed
up on. There's no nothing ever comes out of it.
And it's irritating because what if you could
catch autism With that altered connection, remember
the salience network has the insula, which is
right in here, very lateral, and then the anterior
cingulate cortex, which is part of the medial
prefrontal cortex. It's medial, so it's not as
lateral. But these are the major hubs for the
salience network. That paper found that connections
to here were stronger. That's because of the
diffusion, I think. I don't know if the paper
highlighted that but whenever there's diffusion,
there's just chaos versus the normal, the typical
developed that didn't have these stronger connections
to this sensory motor area. What if you could
catch that and then provide some sort of intervention
to help the living organism, the autistic phenyl
child, to not bias so much to the inside? That's
a conflict though, because how much the autistic
phenotype gets out of being comfortable within
is massive for learning. It's just the social
norms kind of make this more complicated than
what they are, what they should be. The autistic
phenotype can learn at such accelerated rates
because of how much these neural connections,
these wires, biases us to the inside which is
fine so serotonin's role with the sensory map
we'll also do before we wrap up we'll also do
an episode about serotonin's role versus t3 thyroxine
t3 during this same epoch here has massive rows
with specific cells It's underrated and unknown
as well. This is all very fascinating because
they're both from aromatic amino acids that absorb
specific wavelengths of light. So, serotonin
development in the sensory map. Diffusion versus
refinement. Pruning.