Medical Neuroscience explores the functional organization and neurophysiology of the human central nervous system, while providing a neurobiological framework for understanding human behavior. In this course, you will discover the organization of the neural systems in the brain and spinal cord that mediate sensation, motivate bodily action, and integrate sensorimotor signals with memory, emotion and related faculties of cognition. The overall goal of this course is to provide the foundation for understanding the impairments of sensation, action and cognition that accompany injury, disease or dysfunction in the central nervous system. The course will build upon knowledge acquired through prior studies of cell and molecular biology, general physiology and human anatomy, as we focus primarily on the central nervous system. This online course is designed to include all of the core concepts in neurophysiology and clinical neuroanatomy that would be presented in most first-year neuroscience courses in schools of medicine. However, there are some topics (e.g., biological psychiatry) and several learning experiences (e.g., hands-on brain dissection) that we provide in the corresponding course offered in the Duke University School of Medicine on campus that we are not attempting to reproduce in Medical Neuroscience online. Nevertheless, our aim is to faithfully present in scope and rigor a medical school caliber course experience. This course comprises six units of content organized into 12 weeks, with an additional week for a comprehensive final exam: - Unit 1 Neuroanatomy (weeks 1-2). This unit covers the surface anatomy of the human brain, its internal structure, and the overall organization of sensory and motor systems in the brainstem and spinal cord. - Unit 2 Neural signaling (weeks 3-4). This unit addresses the fundamental mechanisms of neuronal excitability, signal generation and propagation, synaptic transmission, post synaptic mechanisms of signal integration, and neural plasticity. - Unit 3 Sensory systems (weeks 5-7). Here, you will learn the overall organization and function of the sensory systems that contribute to our sense of self relative to the world around us: somatic sensory systems, proprioception, vision, audition, and balance senses. - Unit 4 Motor systems (weeks 8-9). In this unit, we will examine the organization and function of the brain and spinal mechanisms that govern bodily movement. - Unit 5 Brain Development (week 10). Next, we turn our attention to the neurobiological mechanisms for building the nervous system in embryonic development and in early postnatal life; we will also consider how the brain changes across the lifespan. - Unit 6 Cognition (weeks 11-12). The course concludes with a survey of the association systems of the cerebral hemispheres, with an emphasis on cortical networks that integrate perception, memory and emotion in organizing behavior and planning for the future; we will also consider brain systems for maintaining homeostasis and regulating brain state.
Pain and Temperature Pathways, part 2
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来自 Duke University 的课程
Medical Neuroscience
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从本节课中
Sensory Systems: General Principles and Somatic Sensation
We have reached a significant juncture in Medical Neuroscience as we turn our attention to the organization and function of the sensory systems. We will begin our studies with the somatic sensory systems, which includes subsystems for mechanical sensation and pain/temperature sensation. But before we get there, it is worth considering first some organizing principles that will set the stage for studies of somatic sensation and all the other sensory systems of the body.
与讲师见面
Leonard E. White, Ph.D.Associate Professor
Department of Neurology, Department of Neurobiology, Duke University School of Medicine; Department of Psychology & Neuroscience, Trinity College of Arts & Sciences; Director of Education, Duke Institute for Brain Sciences; Duke University
If you're following along with the table that I gave you in the tutorial notes for
this session you'll notice at the bottom of the table, there is discussion of a
visceral pain pathway that may come as a bit of a surprise.
So, I want to conclude this brief session talking about visceral pain.
Well, visceral pain Is derived from A delta and C fibers that are innervating
the viscera and such fibers exist throughout all of the body's viscera.
And, the central processes of these axons for the postcranial body for example,
enter the spinal cord, synapse in the dorsal horn, and give rise then to signals
that arise in the anterolateral pathway. Well that's been what had been understood
for many, many years about visceral pain. But more recently some very careful
neuroanatomical studies in animal models. And more recently, some physiological
studies in animal models and even some studies done in people have shown that
there's an additional pathway that runs, not in the anterolateral system, but in
the dorsal columns. So this is I know a bit of a problem for
those of us who like to think that the dorsal columns are all about
mechanosensation. And the anterolateral system is where we
find pain fibers. Now, we have to admit that there is a
small visceral pain component that runs in the dorsal columns.
I say small, because quantitatively, it is a small contribution to the dorsal
columns. But it might not be small in terms of how
clinicians might take this knowledge, and then, develop novel intervention to treat
people that are dealing with rather intractable pain coming from their
viscera. Well, here's what the pathway seems to
look like as best we can understand it. The first order axons, dorsal root
ganglion cells will send an axon in through the dorsal root entry zone.
But they seem to make a synapse with second order neurons that reside right
around the central canal region. This intermediate grey area of the spinal
cord between the dorsal and the ventral horns these second order neurons then give
rise to an axons that enters the dorsal column and ascend to the dorsal column
nuclei. And at that level, there is a synaptic
connection with dorsal column nuclei cells that then give rise to projections that
seem to run along the path of the medial lemniscus.
And they terminate in a part of the ventral posterior complex of the thalamus
that sends input into the insular cortex. And as we'll see in a later session, the
insular cortex serves as a bit of a somatic sensory cortex for the viscera.
Well, this pathway, as I mentioned, has already had some clinical impact.
There are patients that have intractable pain due to abdominal and pelvic floor
cancers. And some of these patients have been
treated effectively by making a very small neurosurgical lesion in the dorsal column
area with the goal of cutting through the second order nociceptive fibers while
preserving as much of the mechanosensory afference as possible.
At least one such patient that has been well-publicized now receives remarkable
relief from his medically intractable cancer pain.
And well, his life was not extended by this procedure, the quality of his life
was greatly improved. Well we've yet to understand the full
significance of this dorsal column visceral pain pathway, but it does raise
some interesting questions. One phenomenon that ought to be mentioned
at this juncture, is the phenomenon of referred pain.
And this is the idea that maybe there's some crosstalk somewhere in the pain
system between the signals arising from the viscera, and those that are arising
from more peripheral structures in the body where all of the skin surfaces.
Well, that site of crosstalk has traditionally been assumed to be the
dorsal horn of the spinal cord, and indeed, we believe that, that is the case.
But, recognition of a visceral pain pathway, such as what I just described
suggest that there may be other sites for crosstalk as well.
Such as the dorsal column nuclei or perhaps even the ventral posterior complex
of the thalamus itself. Well, should that be the case, then
perhaps visceral pain patterns reflects the integration of visceral and somatic
sensory nociceptive systems throughout the entire distribution of gray matter that
receives this input in parallel. Well further studies necessary to totally
sort all that out. But it is worth just considering how pain
is processed in parallel. And when there might be opportunities for
those parallel pathways to exchange information.
And while visceral pain patterns are not really something that we attempt to treat,
they're tremendously useful by allowing clinicians to have some insight into what
might be the true source of pain. Obviously, if you have a patient that is
complaining of left-sided arm and shoulder pain.
One might consider the possibility that there may be a cardiac origin to that
pain. And likewise pain along the midline of the
chest region associated with the sternum or potentially encroaching upon the left
side of the flank might be related to some kind of acidic burning of the esophagus.
So, referred pain can be very useful from a clinical standpoint.
And I hope this tutorial on the anatomy of the pain pathways is giving you just a
little more insight as to why these patterns might emerge.
Well, thanks for your attention. And as I mentioned at the onset, there is
much more that we could study with regard to the pain pathways.
We haven't attempted to look in detail at the second pain pathways.
But I do want us to now to transition to Sylvius.
And give you a chance to recognize what those first pain pathways actually look
like as we see them in the spinal cord and the brainstem.
So, let's transition to Sylvius now go ahead and open up your version of Sylvius
if you have it or feel free to follow along with me.
Welcome back and we're in Sylvius now, so I'm going to open the Brainstem Cross
Sectional Atlas by clicking onto All structures.
And let's go ahead and have a look at the spinal cord first, and we'll consider the
distribution of anterolateral system fibers for the postcranial body.
So here, we're looking at a cross section through the lumbar spinal cord.
Our dorsal roots are entering in the upper part of this image, which is dorsal or
posterior. So here's our dorsal root entry zone, and
we see this really bright region here in the dorsal horn, that's a substantia
gelatinosa. So, out here in the marginal zone and in
the substantia gelatinosa that's where our C fibers are going to terminate.
Whereas more in these deeper parts of the dorsal horn, that's where the A delta
fibers will terminate. Well, from these parts of the gray matter
arise the axons of the projection neurons that grow the anterolateral system fibers.
So, a neuron here at the base of the dorsal horn, let's say this is the left
side of the spinal cord, will grow an axon that will cross in this region of the
white matter. This is what we call the anterior or the
ventral white commissure of the spinal cord.
The axons grow across the midline and then enter the anterior and lateral part of the
white matter here, just to the lateral margin of the ventral horn of the spinal
cord. So this is now what we call the
anterolateral system. So the axons in the anterolateral system
over here on the right side of the image, those axons were grown by neurons that sit
on the opposite side of the dorsal horn. And vice versa for these axons here.
Now, while I have this anterolateral system selected in Sylvia, so I'm simply
going to, now, section up through the spinal cord.
And you'll see that, as we collect up more and more axons, this pathway grows in
size. Now, we're in the cervical cord and we can
see it occupies quite a bit of the white matter in this anterior and lateral
region. As we enter the brainstem you'll now be
comfortable with the idea that additional structures are found that are not present
in the spinal cord. Some of them occupy the ventral part of
the brainstem, including structures like the inferior olivary nuclei out here.
So our anterolateral fibers end up in a more of an intermediate position, but
they're still far lateral. So, we are now in the caudal medulla, as
we ascend through the medulla. These axons sit more or less between the
trigeminal region and the inferior olive. And eventually other components that
occupy the basal or anterior region of the brainstem.
So here is our spinal trigeminal system. We'll get back to that in just a moment.
Here again is our inferior olivary nucleus, and right between the two, is our
anterolateral system. So let's continue to track the progression
of these axons in the lateral part of the tegmentum.
Now, the structures are just to the posterior side of all of these pontine
nuclei and pontocerebellar fibers. And finally, as we get into the midbrain
you'll see that these axons are getting into a more posterior position.
They're still pretty far out lateral, still in the tegmentum.
And where they end up is in a position to supply the ventral posterior complex of
the thalamus, which is right about there. So there is our ventral posterior lateral
nucleus of the thalamus receiving input from these ascending axons from
contralateral dorsal horn neurons. Alright, let's reset.
And consider the organization of the trigeminal counterpart of this
anterolateral pathway. So, this begins at the level of the
trigeminal nerve root. So here is the trigeminal nerve entering
the [unknown] part in the mid pons. You'll remember that the mechanosensory
function of this nerve terminates right here in the chief sensory or the principle
nucleus of the trigeminal complex. But the pain and temperature fibers, they
make a sharp downward bend at this level. And so, what we find is the development of
a compact tract of white matter that is in the lateral part of the tagmentum of the
brainstem. This is a tract made by the central
processes of our nociceptive afferent, so they're present in the trigeminal nerve.
So we have a tract just on the lateral edge of the nucleus and that nucleus is
the spinal trigeminal nucleus with the spinal nucleus of trigeminal complex.
So let's follow this tract on down through the caudal part of the pons and now into
the medulla. And as we progress into the medulla, we
continue to find this well-defined tract, and then, a nucleus that sits just medial
to that tract. Along the way, the axons in the tract are
diving out and terminating neurons that comprise this long column that we call the
spinal trigeminal nucleus. Now, one interesting feature of this
nucleus, is that the closer we get to the junction of the medulla and the spinal
cord, the more this nucleus begins to resemble the dorsal horn.
So in fact, we get to the caudal medulla and now we see a component of this spinal
trigeminal nucleus that looks like the substantia gelatinosa, in fact, we call
this the gelatinosa part of the spinal trigeminal nucleus.
And then, the more medial part of this nucleus begins to look like the base of
the dorsal horn. So, sometimes, we like to say that the
spinal trigeminal nucleus is really an extension of the dorsal horn of the spinal
cord. So maybe that's some help to you
conceptually to recognize that the organization of the second order
projection from the dorsal horn to the thalamus really is quite similar To the
projection from the spinal trigeminal nucleus to it's destination in the
thalamus. So now, we see the dorsal horn again, the
substantia gelatinosa, the base of the dorsal horn.
Okay, well let's now ascend and watch what happens to this trigeminal system.
So, here is our spinal trigeminal nucleus and we have different divisions of it
which are labeled differently is obvious. But now, we've got the most rostral part
of this nucleus in view here and we are about to again enter the level where the
trigeminal nerve hits. So now, we don't have the first order
afferents above this level, because those pain and temperature afferents are
descending. Rather, what we have in the tegmentum is
the second order axons. Now, I haven't indicated the precise
location of this so-called trigeminothalamic tract, sometimes, it's
called the ventral trigeminothalamic tract.
But it's essentially very near the location of the anterolateral system
axons, probably just near the medial edge of these anterolateral system axons right
around there. We know it's going to be in a position to
eventually enter the posterior part of the thalamus and provide input to the ventral
posterior medial nucleus, which is what we see here.
Okay one final point to mention before we conclude this tutorial on the anatomy of
the pain pathways. I want you to recognize the spatial
separation within the nervous system between the pathways for mechanosensation
and the pathways for pain and temperature. We talked about dissociated sensory loss
with spinal cord injury which is [unknown] in part upon the spatial segregation of
those pathways with an ipsilateral pathway in the spinal cord for mechanisensation
and a contralaterally derived pathway for pain and temperature.
In the brainstem, we have a different kind of spatial separation.
We have pain and temperature systems out here in the lateral tegmentum of the
spinal cord. I'm sorry, of the medulla.
But, near the midline of the medulla, we have a mechanosensory pathway, the medial
lemniscus. We don't yet have the facial component,
because we're in the medulla, below the level of the trigeminal nerve.
I say all of this to make the following point.
We will see patterns of strokes in patients that afflict just the medial part
of the medulla, sparing the lateral part, or vice versa.
We may see strobe patterns that affect the lateral part of the tegmentum, sparing the
medial part. And you could imagine what kind of
dissociations you might see in those patient.
One might imagine encountering a patient lets say this is a left side of the
medulla. Where one might find loss of pain and
temperature sensation on the right side of the post-cranial body, but the left side
of the face with no damage at all to our mechanosensory systems.
On the other hand, one might imagine a patient that has damage through the
mechanosensory pathway for the postcranial body, and, no injury to pain and
temperature sensibilities anywhere. Well, these kinds of stroke patterns make
great sense if you understand the distribution of pathways for the various
modalities of somatic sensation. So I hope that gives you some additional
motivation to take on this challenge and make.
Clear and make visible your understanding of this complex clinical neuroanatomy.
