okay we're going to cover the basal ganglia because
last winter we covered it in quite detail in
several different episodes and this is where
movements happen so there's a lot of humans are
constantly doing movements and actions this is
action so the episodes we covered with the basal
ganglia is episode 48 autism and the basal ganglia
motivations movements from learning and habits
episode 49 autism in Parkinson's Parkinson's
is a hot spot right here especially here here
and here we probably won't cover much on Parkinson's
in this whiteboard but we will later I promise
you episode 50 autism in the basal ganglia repetition
sameness and habits and Also, episode 47. We
could include episode 47 here. The autistic phenotype
and how internal calculators shape our preference.
We talk about internal calculators a lot. And
they should. They should be talked about. So
these two specifically, basal ganglia, we're
going to talk about the basal ganglia. This is
one side of the basal ganglia. They're just spots
right now. But we're going to get through it.
Okay? The base of ganglia is essentially five
subcortical areas. Okay? There's input areas
and this is called the dorsal striatum. Input
areas. Markers going out already. The dorsal
striatum is two areas. The cadet nucleus and
the pertainment. Putamen sometimes. So these
two areas receive the inputs. And then there
are also relays. Relays are Globus pallidus external
and subthalamic nucleus. Globus pallidus are
these two. They almost make a triangle. But the
external, because this is going to be center,
and then we'll draw out the contralateral here
in a minute. So this is Globus Pallidus external
and this is the subthalamic nucleus. This is
the thalamus. The subthalamic nucleus is just
basically another assistant for the thalamus.
The thalamus is a workhorse and it needs help.
And then the output areas in blue. Globus Pallidus
internal and Substantia nigra pars fritikulata.
These two nuclei are very identical. Globus pallidus
internal here because it's internal medial and
the substantia nigra pars reticulata. This is
the substantia nigra. This is in the midbrain
the mesencephalon. So if we were to look at it
it would look more like this flat looking at
it from this posterior end but I had to rotate
it up so we can see the reticulata which is here
and then the pars compacta which is so reticulata
pars compacta they have different roles we're
going to get through it these five subcortical
areas orchestrate our movements every movement
besides those funky reflexes that we have if
we hit an elbow or a knee when the doctor hits
taps our knee with a little spike hammer like
thing and it goes every movement is orchestrated
here. So this is why it's important. So we have
the input areas and I'll just go ahead and draw
out contralateral because we're gonna do the
go side. That's a good point here. This is go
no go. This is go no go. This is orchestrating
movements and suppressing movements. So I'll
just draw this out contralateral. Remember, ipsilateral
is one side. Contralateral is both sides. So
we have the cadet nucleus here, and the butamen,
putamen. These are the inputs. We're gonna get,
we're gonna make sense of what the inputs mean.
And then we have the globus pallidus external
on one side. A little relay station. It has hidden
rules. We're going to dissect these hidden rules
for sure because it's missed. It's new. Textbooks
don't teach it. And then the subthalamic nucleus,
just a little flat spot right below the thalamus.
And we have the thalamus. The thalamus is the
target. Remember, it's a workhorse. And the pars
reticulata, the globus pallidus internal. So
why is the thalamus blue? The same as the outputs.
This is the target. This orchestrates everything.
It's a sensory relay station. It receives all
sensations and then it's also on that feed forward
feedback loop. Remember the mini columns. Everything
is orchestrated through the thalamus and then
the substantia nigra pars compacta is also involved.
We're gonna, we're gonna, we're gonna understand
why. This is a modulator. So we can add modulator.
Biggest one, Substantia nigra, pars compact.
SNC, you can see that abbreviated as SNC, and
reticulata is SNR. Lowercase, the C and R are
lowercase. This is the basal ganglia. So what
does it mean? Just real general We'll map out
the ghost side here and the no ghost side here
because these have distinct names direct pathway
equals go Okay, so inputs excitatories projections
come in to the chidot nucleus and The containment
and these orchestrate our movements. These are
conductors They're recruiting, activating, and
turning off and activating downstream regions.
For the goal side, simple. Projections come in
excitatory from the cortex. We're going to map
these out because this is going to sound too
simple. The dorsal striatum of the cardiac amputation
will send inhibition. Everything coming out of
the dorsal striatum is inhibitory. you know about
autism and the lack of inhibitory or a problem
with the inhibitory so it will inhibit the globus
pallidus internal and the porous reticulata that
will in turn while shutting these off allow them
to it will feed up to the thalamus and and that
frees up the thalamus to send projections back
up remember layer four of the many columns if
we have these many columns right remember we
can just map these out like this we have the
the cells the collection of different cells here
and then we have the stellette cells in layer
four and then we have more cells down through
layers five and six remember five is about firing
five a is tonic five b is burst firing then layer
6 has A and B as well. It's a cortical thalamus
so it speaks back to the thalamus and 6B is cortical
to cortical speaking throughout the cortex. So
there's a 5A and 5B based off of the firing and
6. Where is it going? Remember down below 6 is
a lot of white matter tracks. Okay so remember
you have these cells here And also this is where
the spindle neurons are in some of the areas.
Spindle neurons are a little flat and funky looking,
but these are loaded with cells through here.
Whenever the thalamus is freed up, so let's just
go back. Excitatory inputs hit the caudate amputamen.
We'll just discriminate those in a minute. And
that will inhibit the globus pallidus internal.
and the pars reticulata substantial nigra pars
reticulata and that frees up the thalamus inhibit
the thalamus anymore so the thalamus will speak
back up to you know where layer four this is
where the inputs come in on the many columns
then it goes to layer two and three Because this
is where we live. This is where our intelligence
lives, our memory, our experiences, our ability,
and so forth. And then two to three will speak
back down to five and six. How much intensity
does it want to send? And then where is it going?
That's the mini column. This is pretty much the
function here. Every movement, every movement
that we're making is orchestrated through that.
Sounds simple. This is the indirect. pathway
no go stop stop so excitatory inputs come in
to the cadet and to the putamen okay and here
there's a little bit more going on the cadet
and putamen will send signals to the globus pallidus
external and then this will kind of do a lot
of different things but we'll parse out what
this is doing in detail And this will also speak
over to the subthalamic nucleus. The subthalamic
nucleus will shut off. Nope, excite. Will excite
these. And then that allows these output areas,
the globus pallidus internal and the substantia
nigra pars reticulata, to go back to the thalamus.
It will instruct the thalamus to stop. So you
can see there's a little bit more coordination.
for the for the stop for the suppression and
there's timing involved here that we're going
to get into and essentially that's the direct
pathway and the indirect pathway it seems simple
that's a simplistic way of looking at it so let's
talk about the input areas because this is going
to be huge what are these what are those so the
input areas yeah That's a good way of thinking
about it. Because these are input areas of what's
coming in. So the biggest thing here is the cortex.
This is the biggest thing that sends signals
excitatory, they're always excitatory, to these
areas. The second one is the thalamus. The thalamus
will send inputs, projections back to the dorsal
striatum. And a lot of this is This is all excitatory
as well, but this is the thalamus is telling
it to pay attention Something important is or
unexpected is about to happen. So Help be on
alert here because remember the thalamus is always
asking and needing help okay, this will also
help provide a little bit of arousal and context
to what is happening because It's a workhorse
the thalamus is a workhorse The second thing
or the third thing is Substantia Nigra Pars Compacta.
Here, this is a big input area because we're
going to talk about the specific cell types,
medium spiny neurons here and make sense of like
so -called typicals versus autistics. So, Substantia
Nigra Pars Compacta is dopamine. D1 and D2 dopamine.
This is excitatory and D2 are inhibitory. So
it's modulating. It's modulating the attention,
the intensity and so forth. These use DR1 and
DR5 receptors. Dopamine receptor 1, dopamine
receptor 5. Dopamine only has five receptors.
R2, 3, and 4. Substantia nigra pars compacta.
It's major projection, major target. is the dorsal
striatum. This is dopamine. We also have the
ventral tegmental area for dopamine. So dopamine
is very important. This is telling the dorsal
striatum that this is good or this is bad. It's
providing some value and intensity. It will amplify
it if needed. Okay, it's teaching it what is
worth doing. Do I want to do this? And so forth.
Also, as modulators to Alessero, these are the
three biggest input areas to the caudate and
the putamen. But also, there are modulators like
serotonin. So the dorsal graph A for serotonin.
This is providing some information here to say,
have patience. Just give it a moment type of
thing. Okay? That's serotonin. That's what it's
doing. So, you also know about like the mood
thing. So, I'm okay right now. In this situation,
you're okay. Or, no. And then, choline. Not...
So, it's acetylcholine, essentially, but it's
not from the forebrain. The nucleus basalis of
Minert does not really project to these areas
for the choline. We've talked about in the mesencephalon
episode that There's also little regions down
in the brain stem, the mesencephalon, that releases
choline. Remember the Edinger -Westphal nuclei
that's heavily involved with cranial nerve 3
as well. There's little subdivisions down here
that also release choline. And this is one of
them. It's the very long and complicated nomenclature.
But PPG... L, T, D, and so forth. This is helping
shift between focus and attention. It's helping
provide a little bit of flexibility. Pay attention
to this type of thing. You know, that's what
a stable choline does. And then even less than
these two are things like from the limbic areas,
like the amygdala and hippocampi. So most of
these are excitatory but there's an unknown role
with the globus pallidus external that's speaking
back up to the dorsal striatum we're going to
get there in a minute but for now we need to
understand the the signals coming in from the
cortex because that's that determines everything
so let's just map this out from a side view and
I will use just one color for all the subcortical
areas if we're looking at this from the side
let's say the thalamus is here now there's a
reason I'm not going to color all of this in
because the thalamus is very midline it's very
medial so we're going to have to work out this
way we're going to have to work out this way
and you can see there's a lot of overlap so it's
going to be hard to map this out laterally if
we're looking at it like this this way These
are lateral. So yeah, it's gonna be hard now
for me to draw this out But the cadet is long.
It has a tail it even wraps around and connects
kind of to the to the amygdala So this is it's
like a shrimp. It reminds me of a shrimp So this
is here now. It just depends on how deep you
want to go if you're looking at it from behind
is how much this is going to show up and which
part because if you're looking at it from this
way you'll be able to see different parts of
it different it's going to look bigger but the
putamen is right here and these are connected
just briefly so cadet nucleus putamen thalamus
right here so if you notice the putamen is going
to block the globus pallidus so the globus pallidus
would sit just right here okay this isn't as
important so this is the thalamus septalemic
would sit about right here and then the reticulata
and compacta would be down here remember we drew
out we drew out the brainstem if you're looking
at the brainstem like this if you just want to
slice it open that way you can see the pars reticulata
and compacta are in the kind of anterior part
of the mesencephalon so if it's like this if
the brain stem remember if we have the pons a
little football shape and then the brain stem
goes down so mesencephalon it would be like here
superior colliculus inferior colliculus so substantia
nigra compacta and reticulata here and then we
would have the cerebellum like this cerebellum
is going to have a role you know motor movements
fine tuning it's going to have a role we might
get into it so the cortex here would be all of
this area all right so the occipital lobe parietal
the sensory motor which is here parietal is back
through here and then the frontal cortex the
prefrontal cortex okay so the major part coming
into here is the sensory motor area which is
essentially here. Remember we have things like
the somatosensory cortex here and then the sensory
motor here we have the frontal eye fields are
up here frontal eye fields um sensory motor there's
a lot of habits living up through here okay and
then we have the somatosensory This is a large
part. This is probably the second most inputs
coming in. This is probably the most inputs.
Remember, we love to build habits and store them
up through here. We love repetition and habits.
This is who we are. This is why we're covering
this. And then some prefrontal areas. Remember
the dorsal striatum? No, the dorsal lateral prefrontal
cortex up through here. This area of the prefrontal
cortex right through here. Okay. and then the
orbital frontal cortex right through here right
here this is providing this is good with working
memory and providing a plan so it will project
down through here to kind of give it some instructions
on what to do based off of this what we're encountering
the orbital prefrontal cortex here remember it's
mostly sensory it has a a lot of specificity
of what the living organism wants and kind of
desires in real time is providing value and reward.
Is this worth it or not? With the specificity,
if you want, let's say, if you're thinking that
you need caffeine, the orbital frontal cortex
is going to tell you exactly the source of the
caffeine that you want. Maybe I want coffee.
Maybe I don't want coffee. Maybe I want tea or
whatever. That's going to help this out. And
then the medial prefrontal cortex is in through
here. Remember, the ACC is here. And then the
insula would live right through here, the anterior
insula. Not involved though. This is involved.
This is involved because this is a big calculator.
This is conflict monitoring and evaluating risk
reward. So it's providing constant updates. This
isn't just a one -time thing and you're done.
This is constant. These two networks are dancing
around constant. There are so many. This is a
lot of electrical activity and projections right
here. And it will also allow it to update because
you're evaluating reward and the environment.
Okay, that action didn't give me what I wanted.
I have to do something else. The ACC will help
conduct that, adjust your behavior. It's also
doing the conflict monitoring and so forth. And
then the parietal lobe is back here, remember?
So if this is the occipital, and then the parietal,
see we're just building the brain here. And the
temporal lobe will run through here, so we're
just mapping out the brain here. The parietal
lobe will also send some inputs through here.
And it's going to be, because the parietal is
sensory integration a lot, it's providing some
context dependent cues. Okay, look here or don't
look here. What was that noise type of thing?
That noise got loud and so forth. So it will
help orchestrate movements here. So these are
the biggest cortex inputs coming in. So. What
does that mean? We are all different. This conversation
today is based off of who we are, what we are,
what we do, what we like and so forth. This is
why we're so different. So let's just really
zoom in here because this is getting way too
long. Let's just zoom in here, okay? Let's just
extract a single cell from one of these two areas,
okay? First thing I want to say though is, the
more medial you are in these subcortical areas,
and even in the cortex, more likely it is something
new, novel, or goal -directed. And then habits
will live outward, lateral. So the putamen is
more about habits. So it receives a lot more
inputs from that sensory motor area because we
love to send our information and our abilities
to this area. So more goal directed through here,
habits go lateral. If you think about the evolution
of the living organism and humanity, it makes
sense because we had to have motivation to do
and get what we want first. And then we can shift
those over. We can shift those over. And I think
that frees up space for the goal -directed behavior.
We can all understand that change is hard. Because
we're going to talk about morphology and these
synaptic connections. So let's just extract a
single cell. I'm just picking one. It's just
a general example. Because these are medium spiny
neurons. So we have the cell body, the nucleus,
okay? So let's just say this is a cell. Be it
good or bad drawing, I don't know. The cells
in the dorsal striatum are very special. They're
called medium spiny neurons MSN and that's why
the dopamine is a big part of this with the D1
D2. So if you think about this, these are like
branches or limbs off of a tree and then these
are dendrites, okay, and then they have little
spines on them. Okay, all of these spines are
little parking spots. The projections coming
in from those other areas that we drew out in
the cortex, or wherever it might be, will land
on a specific spine. Okay, now with the medium
spiny neurons, spines are bigger. They're just
a little bit larger than normal cells. So they
will look more, if you look at a tree. okay this
is an easy example some trees are loaded with
leaves and some are not okay these medium spiny
ones are like a nice oak tree nice oak tree in
the summer okay now let's really zoom in again
so let's look at let's look at this one let's
look at this branch this dendrite and then this
spine right here let's just say this is the spine
okay This specific spine will receive a specific
projection coming in, and it will mean the same
thing every time. The thing that connects to
this, that sends a projection to this spine,
will be the same. Okay, so we have the pre -synaptic,
the clef, and the post -synaptic. Okay, this
Connection here will mean the exact same thing
every time. So it's providing a little bit of
update information. So that's what we're talking
about. These neural correlates. So let's just
say this came in from the sensory motor area
and it projected down to the putamen because
we're building a habit and it's hitting this
cell with that specific spine. So this information
will come in, signal to this spine and this cell
will know what to do with it and how to help
conduct these downstream actions or inactions
which is still inaction because you're suppressing
the target. You're suppressing movement. It's
what the living organism is doing. This is why
things like motivation or do you define motivation
or your central nervous system does because as
these are firing with repetition these grow so
post -synaptic or pre -synaptic and post -synaptic
okay and there's like little parking spots here
remember like an mda and amp a amp a is going
to be huge here it's huge with learning because
this is what we're talking about as You build
repetition and habits, these things get bigger.
This is called morphology. It's synaptic plasticity.
So let's compare this size. Remember, let's just
say the inside diameter here versus something
that you don't do very much. You're not very
good at so forth. Maybe you want to be good at
it. Maybe you want to. but you just don't have
the skill set yet. This in the central nervous
system is going to be preferred. The brain does
not like to work. The central nervous system
does not like to work. It just likes to respond.
So when things are larger, like this, that is
going to get the privilege. So this cell that
is in this nuclei, that means this information
will connect and carry out the movement with
the autistic phenotype these cells are different
these medium spiny neurons are different okay
so dendrites are a little bit larger and the
spines have a unique specificity and special
privilege so this information coming in from
the cortex will sure fire over anything else
Because all of these different flexibilities,
you can call these different spines flexibility,
that the living organism might have, is not there
with the autistic phenotype cell. So this certain
spine, let's say, is larger like this and just
limits flexibility and causes sameness or habits
will always win. This is a big part of the autistic
phenotype. This is why, autistic or not, you
don't necessarily define motivation. These neural
correlates and connections do. This is why change
is hard. The central nervous system is going
to determine what you do. Now I'm not saying
that you can't reverse this I can't say that
I'm not saying you can't change and build better
connections through here maybe more connections
maybe strengthen this one up because it's more
preferred and these receptors will hit I'm not
saying that at all but with the autistic phenotype
the dorsal striatum and these sensory input areas
and the lack of the prefrontal areas coming in
to the dorsal striatum are limited Remember the
ACC. We talk a lot about the ACC. It's action
selection. Next episode is about the basal ganglia.
We'll parse out this area right here. The globus
palate is external because this is sending updated
feedback to the dorsal striatum and is not well
known. And also the subthalamic neculus. This
little thalamus helper. It's receiving direct
inputs from the cortex as well. to help providing
it some help, helping the thalamus respond and
so forth. But the big takeaway here is the kind
of so -called abnormal medium spiny neurons and
the limited flexibility with connections coming
into the dorsal striata. Remember, this is just
extracted out in one of these nihilas and then
the connections happen. The big takeaway as well
is this one spine receives information from one
presynaptic area and is providing information
and as which each synapses with each connection
coming down into from the cortex down to the
dorsal striatum it's building a summary each
synaptic connection builds summary summary summary
and it's building a bigger story overall and
then it gets to the time where it's orchestrating
the go or no go movement which is speaking back
up to the cortex and it's just a constant feed
forward feedback loop this is constantly going
i don't know if i covered everything i wanted
to cover though i do want to say this with the
autistic phenotype because this is a big thing
this is a big thing because you can now know
about b2 it's just on samus and flexible adherence
to routines or ritualized patterns of verbal
or nonverbal behavior speech is heavily involved
in here speech will run through here and b3 highly
restricted fixated interests that are abnormal
in intensity or focus strong attachment to or
preoccupation with unusual objects excessively
circumscribed or perseverative interest this
is autism b3 is the core of autism restricted
fixated interests that are abnormal in intensity
or focus right here. We build habits. We have
these so -called splinter skills. Asperger's
little professors. Because these connections
are constantly firing and it's easy for us to
sit here. Remember the sensory processing with
the the amount of being able to absorb information.
That information goes here. We're kind of mapping
this out. Basil Ganglia, do you define your motivation
or not?