>>Kevin Patton:
V.S. Ramachandran, the prominent neuroscientist
and author, once wrote, "The adage that fact is stranger than fiction seems to be especially
true for the workings of the brain." >>Aileen Park:
Welcome to The A&P Professor, a few minutes to focus on teaching human anatomy and physiology
with a veteran educator and teaching mentor, your host, Kevin Patton. >>Kevin Patton:
In episode 139, I talk about a new discovery and nerve signaling in the brain, a possible
new model of brain fu
nction, and how we can help our students understand core concepts
of chemical signaling and signal transduction. A couple of years ago, in the journal, Science,
there was a very interesting discovery about nerve signaling that was published. It has to do with the complexity of brain
function, specifically in nerve signaling. Now, this is something that goes beyond that
basic story of nerve signaling that we tell our students about how computations work in
a nerve network, that is at the neuron l
evel, neuron and synapse and network level. We see that there are inputs that come in
along the dendrites and soma, and they may or may not travel all the way to the axon. But if they do, it's going to determine whether
an action potential begins in the axon. And we know that action potentials are all
or none events. So we know if it starts at the beginning of
the axon near the soma, then we know that it's going to travel all the way down to the
end of the axon. So what happens in those dendrite
s really
is where the decision making is occurring, where the computation is happening, because
that's going to determine whether we get a signal go forward or not. So we have that. That's our basic story. But what they discovered a couple of years
ago is that in layers two and three of the human cortex, where we have our pyramidal
cells and where many neurobiologists believe the complexity that's going on there is really
what makes us uniquely human or makes our brain a uniquely human brain. An
d so what they discovered is dendritic action
potentials that are occurring there, not the typical local potentials that we would expect
to see along dendrites and the soma in any part of the nervous system. These are dendritic action potentials. And so, yeah, they are going to continue to
travel and get to the axon we know. But an interesting thing about them is that,
unlike those other action potentials that we normally think of, they are graded. And what that means is that they're not always
going to get to a certain peak the way we normally think of an action potential. They could have a lower amplitude or a higher
amplitude, depending on the pathway and the circumstances and so on. So that makes it kind of weird. But that's not the only thing that makes these
weird. Number one, they're in a dendrite and they're
an action potential. Number two, they can be graded. But secondly or thirdly. Boy, I can't even count. I don't think my dendritic action potentials
are working. Thirdly, wh
at triggers them, the mechanism
behind them, maybe is a better way to say that, is the influx of calcium ions. Normally when we're looking at an axon, what's
the mechanism? It's the influx of sodium ions that causes
that shift in voltage, that becomes the peak of the action potential. But in dendritic action potentials, what is
happening is calcium channels are opening, and calcium influx is what triggers the creation
of the instance of a dendritic action potential. And so that's different. I me
an, that's not highly unusual. We see calcium causing shifts in membrane
voltage in muscle cells, for example. So yeah, that's something that happens in
nature, but we didn't expect it to happen here and under these particular circumstances. So all of that is kind of weird. But the importance of it is something that's
very profound, I think. And that is, it enables processing, decision
making at a more complex level and in a simpler or at least a different way than we expected. And so this might
be part of the key to understanding
the uniqueness of the human brain. Now, who knows, we might end up finding this
in other brains somewhere else, but then that would make them complex and in this unique
category, I guess, as well. So how does it do that? How does it fit in and change that computation? Well, first of all, we start with this idea
or this model of looking at the brain as if it were a computer. And of course, it's not a computer. And like any model, that falls apart at certain
le
vels. But it's a widely used model right now. When we have nerve signals coming to a neuron,
they're going to be coming in by way of synapses on the dendrites and on the soma. That's where we're getting signals from other
neurons. And those signals, they might poop out before
they get to the axon. And if so, then that's the decision that we
get. We shut it off. The switch gets turned off. And that's partly how computers work with
their little transistors and so on too. They're like little gates
that acted like
a gate that turned off the signal. If the signal, coming into the dendrite gets
to the axon and triggers those voltage-gated channels there, then we'll have an action
potential. And that will get to the distal end of that
axon, and now that's the switch being turned on. It's a gateway that allowed the signal to
get through. When we use the lingo of computation, we normally
think of axons as being able to send AND messages where signals coming in from the dendrite
and soma, they a
re summated and maybe they work together, and they can send the signal
forward. That is if signal X and signal Y are sent. Then together, that's enough to trigger those
voltage-gated channels, and the signal gets sent forward. Or we could have a situation where we have
multiple connections to dendrites. And that's certainly going to happen in these
pyramidal cells in the cortex, layers two and three of the cortex. And so we get something called an OR message
possible. That's where if we get a si
gnal from one pathway,
then that's going to be enough to send the signal all the way through to get to the beginning
of the axon and trigger that action potential and send it through. But we could also get a sufficient signal
from a different pathway. And when that comes in through the dendrite
and gets to the beginning of the axon, if that's sufficient enough, that's going to
trigger the voltage-gated channels. And yes, we're going to get a signal. So a shorthand way of saying that is, if we
ge
t a signal from X, then the message gets sent along. If we get a message from Y, the message gets
sent along. So it's X or Y. So we can set up situations here. We can set up pathways where you need both
X and Y, and then the signal will get sent. Or you could set up a situation where either
X or Y could send the signal forward. So that gives us quite a bit of flexibility
in how that network is going to work and what kinds of signaling, what kinds of decisions
are made, what kind of computations
are made. But in complex computer design, there are
other kinds of signal processing that can occur. And one of those is called the X-OR gateway. The X stands for exclusive. So what that means is it's an exclusive-OR
option. So remember or is X or Y, either one is going
to trigger it. Exclusive-OR means that X or Y, but the possibility
of turning off X or turning off Y. So we're going to need another kind of signal
that's happening along with the main signal. And that signal is going to tamper o
r modify
whether this signal or that signal, it really can get the message through. So I realize I'm oversimplifying this, but
the idea is that those kinds of computations can happen in the nervous system. We can see them happening in the nervous system,
but only if there is a network of neurons that are connected with each other and taking
on those various aspects. In other words, that separate signal that
is needed is happening in another neuron, and that's what's allowing either message
X or
message Y from getting through. Well, here we just have one pyramidal neuron
that's having its usual typical potentials. Alongside that are these dendritic action
potentials, and they're acting as the modifier. So what we're saying is, using just single
cells, we can perform the complex functions that are associated typically with a network
of neurons. So how do you pack more neurons into a smaller
space? Well, you arrange it so you don't need all
those neurons. So you have neurons that have the
se weird
dendritic action potentials that allow them to act like multiple neurons, at least in
terms of their processing power. So looking at neurons and networks of neurons
as if they were a computer processing system is a good idea in general. But there are neurobiologists who get down
to this level of figuring out the ons and offs and modifications of these switches and
so on. And what they're telling us by the discovery
of this dendritic action potential and the observations they made of the
m is that, wow,
there are some cells that can do some things that other cells can't, and that makes them
work in a much more complex way than usual. So circling back to what we tell our students,
number one, promise me you're not going to tell your students about this. But if they ask, if the discussion goes down
that road, now after having read this research, you'll be able to say, "Well, yeah, there
are exceptions to these basic principles that I've been giving you, but they're in very
special
cells that do very special things, and possibly exist only in humans." The computer is often used as a model for
the human nervous system, particularly the brain and its complex functioning. I think it's important for us to understand
that that model is a recent model. In the early days of neurobiology when we
were first beginning to understand that neurons have a role in the nervous system and what
that role is and how the nervous system works, in those early days, we often used a telegraph
sy
stem as a model for the nervous system. If you're not familiar with a telegraph system,
it's simply a wire stretched across a long distance. And by creating an electrical signal in that
wire, you can produce a tap or some other kind of signal at the other end. So basically, you switch it on, switch it
on, switch it on, or switch on, off, on, off. And a guy named Morse came up with a whole
code, the Morse code, where you could send telegrams, that is a telegraphic message across
the wire where it
was just a series of clicks, short clicks and long clicks, and a certain
combination can be interpreted at the other end. And so that was used as a model for sending
signals in the nervous system. And then as technology got a little more complex
and we started building telephone systems, we start using that as the model for the human
nervous system. And then as time went by, we realized, well,
it's more complex even than that. And oh, look, we have computers. That's a good model. And so there a
re very many aspects of computer
function that we're seeing that there are similar or analogous things happening in the
human brain. But as I pointed out way back in episode 112
when I was talking about the idea of using models and codes for things in A&P to help
us understand those things. And really, models are used a lot in science
to help scientists understand what it is they're looking at and form new quests, new questions
that is, on what to look at next and fill out and expand those disco
veries. So models are analogies that help us understand
things. They help us learn things. They help us discover new things. But they're just models, they're not the concepts
themselves. They're not the discoveries themselves. So it's important to always be open to setting
aside older models and using new models, or maybe even having several different models
that we use to look at several different aspects of whatever it is we're trying to learn. So there's that part of it. But I want to introdu
ce to you a new model
of the human nervous system that is probably so wacky, it's going to turn out to not be
anything close to reality, but it kind of gives us the idea that there are other ways
of thinking about how the nervous system works. And this comes from an essay written by the
psychologist, Robert Epstein, who's kind of known for stepping outside of the mainstream
occasionally and helping us understand things in a different way and think about things
in a different way. And here he is
not exactly proposing this
new model, but setting it out there as something to just hold onto and think about, and not
actually apply to the human brain right now, but don't disregard it because it could lead
us down a pathway that we otherwise wouldn't have gone down if we're sticking so closely
to that computer model. And what model is it that he's putting out
there? He calls it the transducer model. Now we know what transduction is, right? We talk about that core concept a lot in human
anatom
y and physiology. We talk about how a chemical signal, for example,
a neurotransmitter is transduced to become a signal on the other side of the synapse. In other words, a neurotransmitter crosses
the synapse, it hits a receptor, signal transduction occurs in that process of that receptor reaction,
and it produces a reaction in the postsynaptic cell. We know that hormones are involved in signal
transduction with their target cells and produce some effect in the target cell. And we see sensory tr
ansduction happen all
the time. We see where different wavelengths of light
and frequencies of light, they're transduced into information that eventually gets to our
brain and is interpreted in a certain way. Sounds are transduced by the auditory functions
that begin in our ear. We have tastes and smells and stress and other
kinds of sensory stimuli that are transduced and become part of our sensory awareness somewhere
along the line. So what Epstein is saying is, what if we thought
of the brain
as a transducer rather than a computer, a two-way transducer where it's
sending information out and getting information back. So one sort of way that he imagines this is
to think of our brain as sort of like a mobile phone where there's all kinds of things I
can do with my mobile phone. I can get all kinds of stored information. And some of that information is actually stored
in my phone, but a lot of information I would need to get from outside the phone. I would need to tap into a database so
mewhere
on the internet, for example, and search for that information and find it, and then apply
it in whatever way I'm going to apply it. And he's saying, maybe we do that. Maybe we send information out of our brain
and then bring information back into our brain. And maybe not everything is stored in our
brain. Maybe some things are stored in our brain. And you know, neuroscience has yet to explain
exactly how all of our memories are stored, the exact mechanisms where they're stored,
where the
y're stored, how they're stored. Now, a lot of it's been worked out, but not
nearly enough to really understand the process. So he's saying, well, what if we can't understand
the process because we're limiting ourselves to looking in the brain? In other words, if we take a mobile phone
and look at it, we can't really explain everything because not all that information resides there. Not all of the processing that our search
engine is doing on the internet, that's not all happening in our phone.
A lot of that's happening somewhere else on
a server somewhere. And so the question then is, where are the
servers that our brains are tapping into and sending information to and getting information
from? And well, that's a big question, isn't it? That's why we're not adopting this model,
are we? No, because we don't know where that is, or
if such a thing exists, such a mechanism exists. And he throws out there, I don't know if he
really sees it as a serious possibility or just the idea that sci
ence has been discovering
things beyond our conscious awareness. And he throws out there this idea of other
dimensions, which physicists, many physicists at least, will tell you absolutely do exist. There are these other dimensions, maybe parallel
dimensions, maybe there's several possibilities, some of which apparently have been shown to
exist in some way or shape or form. Can we completely eliminate the idea that
maybe there's a way that our brain is tapping into that? Maybe there's some kind
of little quantum
thing going on where we're dumping memories into another dimension, and then when we need
them, we pull them back out of that other dimension. Maybe some computations or processing or searching
or some other kind of algorithm is happening in that other dimension, or a parallel universe,
or some sort of shared or networked consciousness, or who knows? We don't have to know that part of it yet,
not to simply start asking different questions about the function of the brain that go
beyond
the current ways of thinking. Maybe that's part of why we biologically have
had such a hard time pinning down some of the complexities of human consciousness and
the evolution of languages and things like that. So he is sort of just throwing that out there
as, what if we think about the brain as a transducer rather than solely as a computer? And I'm thinking that is wacky. I'm not ready to adopt it yet. I bet you aren't either. But I don't know. It's just fun to think about, isn't it? Ch
emical signaling and transduction of those
chemical signals are core concepts in human anatomy and physiology that show up time and
again throughout many different topics in our course. For example, in the nervous system, when we're
talking about chemical synapses, of course, there's a neurotransmitter that when it hits
the postsynaptic membrane, it needs to be transduced. And then we get an effect, we get a result
of that signal, we get a reaction to that signal. The same thing happens with hor
mones. When they hit their target cell, that signal
has to be transduced and then we get a change in that target cell. And we see that in the immune system, where
various cytokines are sending signals to various target cells, immune system cells, for example. And that signal needs to be transduced. So we see all kinds of signal transduction
occurring in various different ways, shapes and forms throughout the human body. And as with any of the core concepts, these
are concepts that we need to hel
p our students understand are repeating, that they do occur
in many different areas of the body. So when they show up, we need to find ways
to help them recognize those core concepts as concepts they've seen before, as mechanisms
that they've seen operating before, but in maybe a very different context. And by doing that, they're going to understand
both contexts, the story that's unfolding in both contexts much more deeply than they
would have if we keep them separate. So that's, I think, part
of our role as instructors,
is to be connectors, to help the students connect those core concepts. So I think that should be a goal of ours. But also, we need to make sure that our students
know that that's their goal too, is to connect those concepts, is to start looking for those
connections themselves. And I've talked about various specific strategies
such as running concept lists, for example, and concept mapping, that students can help
themselves do that and see those connections. And we ca
n help our students do that by modeling
those strategies ourselves in our teaching and in our discussions and in our advice that
we give students in how to study and how to learn anatomy and physiology. I also want to point out, at this moment,
that transition that we make from nervous system function to endocrine function in our
courses, and I realize that not everyone teaches the topics in exactly the same sequence. There's sort of a common sequence that many
of us use, but a lot of us modify
it from time to time. So not everyone does it this way. But in many A&P courses, a discussion of the
nervous system and learning about the nervous system is then immediately followed by endocrine
concepts and understanding endocrine hormonal signaling. And one of the benefits of that is that we
can take this signaling process in one context that is the nervous system, and transport
many of those core concepts right over to the discussion of endocrine regulation. And that transition period where
we're just
beginning that discussion of the endocrine system, having so recently explored the nervous
system, that's a good place to stop and talk about connecting the core concepts across
topics, and use this as an example of, look at nerve signaling, look at hormonal signaling. There are some differences, but there are
some similarities too. They're basically the same concepts, but they're
going to play out in different ways and in different contexts between the two. And it's not just the conc
ept of signaling,
but the structures that are used in signaling. There's some similarity too. And let's start there, with structures. Something that I always point out to my students
is there are some, what we call endocrine structures that are producing chemical signals
that are hormones. I mean, they literally are hormones because
they're acting like a hormone. And that's our definition. It's a functional definition of a hormone,
is a secreting molecule, secreted into the bloodstream to have a
n effect outside of the
tissue that produced it. When we are looking at the neurohypophysis
and we're looking at the adrenal medulla, and we look at the pineal gland, and I know
the other pronunciation is pineal, but I like pineal because it reminds me of a pine cone,
and that's what it's named after. So all of those glands are really, in a way,
modified neurons. They're secreting what would otherwise be
considered a neurotransmitter, except that there's no synapse there. There's no postsynaptic
cell right there. So they diffuse into the bloodstream, and
then they find that postsynaptic cell, which is not really postsynaptic because it's not
part of a synapse, it's the target cell. So that's what replaces the postsynaptic cell,
is the target cell. But it's still signal transduction and still
works the same way of that other chemical signal transduction mechanisms work. At least in general, it works the same way. So we can see that there is a connection right
away between those two syst
ems. Conceptually, at least, there's a connection
because some glands really are just modified presynaptic neurons. But let's go to the functional side of things
because there, I think, we can even more clearly see the connection, the conceptual connection
between nervous system regulation and endocrine regulation. And by doing that, I think our students can
more easily identify the different kinds of regulation and how the nervous system and
endocrine system are complimentary systems in terms o
f regulation. One similarity we can point out is in the
nervous system, it's all about regulating effectors. And one of the general goals is to help maintain
homeostasis. And in the endocrine function, we see that
it's regulation of effectors to maintain homeostasis, it's the same. So they have the same overall function. I mean, we're oversimplifying the function,
of course, but we're at the beginning of the story, so we want to do that. Basically what we're doing is regulating effectors
through
out the body. Which one is it, endocrine or nervous system
doing that? It's both of them doing that, but they're
going to be doing it in different ways. When we look at the endocrine system, we see
that, well, there are regulatory feedback loops that operate, yeah. And we can call those endocrine reflexes if
we want, those feedback loops. And then we look at the nervous system and
we see, yeah, there are regulatory feedback loops that operate there too. And we might call those nerve reflexes whe
n
those occur. So yeah, there's some similarity there too,
at least in the way the information can be processed in both those systems. And then we look at the endocrine system. It has effector tissues, those we call either
endocrine effectors or target cells. Virtually all tissues are target cells of
one or more hormones. Then we look at the nervous system and we
see, well, there's all kinds of nervous effectors, and they include mostly muscles and glandular
tissue, but we know there's some othe
rs like adipose tissue and so on, but they need to
be connected to the system. So the endocrine system, these endocrine effectors
and these target cells throughout the body and the nervous system, well, you got to be
hooked up to a synapse. You got to be in the right place at the right
time. So we're going to see postsynaptic cells being
sort of the target cells of the endocrine system or equivalent to the target cells in
the endocrine system. So there's a similarity there too. I always use a ta
ble, by the way, that compares
the two, and we kind of go through that as a group, and I sort of unveil the different
rows of the table as we go through so we can kind of predict and discuss them as we go
through, so that it's not just reading through some facts, but actually figuring out the
facts. And then like, oh, yes, we were right. Sort of like in Jeopardy, oh, I guessed right. Another thing that we can look at is the chemical
messenger itself. In both places you have a chemical messenger,
right? In the endocrine system, the chemical messengers
are called hormones. And in the nervous system, the chemical messengers
are called neurotransmitters. So in that way, they're alike. And we have, in both systems, cells that secrete
the chemical messenger. So those would be either the glandular epithelial
cells or the neurosecretory cells, if we're talking about the endocrine system. And if we're talking about the nervous system,
those are the neurons, the presynaptic neurons. And then her
e's a big difference between the
two. If we look at the distance traveled by that
chemical messenger and the method of travel of that chemical messenger, now we see some
big differences. In the endocrine system, it's a long distance
that's traveled by the hormone, and the method is by way of the circulating blood. The nervous system on the other hand, has
a short distance for that chemical messenger to travel. That neurotransmitter goes across a microscopic
synapse. And so that's diffusion and i
t's a short distance. So there's a contrast there between the two. And then we look at, well, where are the receptors
located in the effector cell? Well, in the endocrine system, on the plasma
membrane or within the cell is where we're going to be finding those receptors. And it's pretty similar in the nervous system. It's just on the plasma membrane, we're not
going to be receiving the neurotransmitters inside the postsynaptic cell, even though
that's an option in the endocrine system. So again
, we're back to really pretty similar
scenarios or strategies or mechanisms that are operating there. And then we look at the characteristics of
regulatory effects. And in the nervous system, the students would've
learned that the effects usually appear rapidly, but they're short-lived. Unless we keep them going, they don't last
very long. And now that's in general, of course. And then we look at the endocrine system and
we say, well, it takes longer for them to appear because they have to get i
nto the blood
supply, they have to circulate around, finally hit their target cell. So it just physically is a longer distance. So yeah, it's going to take longer for the
regulatory effects to appear, but because the hormones kind of linger for a while and
they don't all hit the target cells right away, and they kind of go back around again
and come back. And yeah, there might still be some left in
the blood there, they're prolonging that effect. Now, within that group, when we look at hormones,
we see that some produce effects sooner than others, some last longer than others. So yeah, there's a range of activity within
that. But when you're just looking at a very simple
level and comparing endocrine versus nervous, we can say that endocrine is slow, but long-lasting. And nervous system effects, they appear rapidly,
and they're short-lived. That's just kind of an approach. It may or may not fit into the way you do
things in your course, but I think that's a good opportunity for us to n
ot only make
that transition from nervous system to endocrine, but in doing so, look at some of these core
concepts of chemical signaling and signal transduction and how they operate similarly
in the two different systems, and how they also sometimes play out differently in the
two different systems. Well, let's see. In episode 139, I put on my thinking cap and
shared some ideas about how we can help our students understand the core concepts of chemical
signaling and signal transduction in diffe
rent contexts. And before that, I briefly described the transducer
model of brain function, a wacky new idea that psychologist, Robert Epstein, thinks
may help us work out where we're stuck in understanding how the nervous system works,
and especially the brain, in those complex ways that are uniquely human. And we started this episode with a new discovery
and nerve signaling in the brain called dendritic action potentials that involve the calcium
mechanism instead of the sodium mechanism, and m
ay help explain the complexity of human
cortical function. Now, as always, I have links for you for all
these topics. If you don't see links in your podcast player,
go to the episode page at theAPprofessor.org/139. And while you're there, you can claim your
digital credential for listening to this episode. And don't forget to call in. Please call in with your anecdotes, tips,
and questions at the podcast hotline. That's 1-833-LION-DEN, or 1-833-546-6336. Or send a recording or a written message
to
podcast@theAPprofessor.org. I'll see you down the road. >>Aileen Park:
The A&P Professor is hosted by Dr. Kevin Patton, an award-winning professor and textbook author
in human anatomy and physiology. >>Kevin Patton:
Listening to this episode may cause permanent changes in the brain.
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