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.
Functional Plasticity In Cortical Maps
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Medical Neuroscience
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从本节课中
The Changing Brain: The Brain Across the Lifespan
This module represents another turning point in Medical Neuroscience. Now that we have surveyed human neuroanatomy and our sensory and motor systems, we are ready to take a step back and consider how this magnificent central nervous system came to be the way that it is. We will also learn how the brain re-wires itself across the lifespan as genetic specification, experience-dependent plasticity and self-organization continue to interact, re-shaping the structure and function of neural circuits throughout the central nervous system.
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
Okay, I think we're ready to switch gears here, in talking about how the brain
changes across the lifespan. I'd like to turn our attention to a
couple of specific contexts. Beginning first with the plasticity of
sensory and motor maps in the brain where these plastic phenomena have been best
studied and best understood. So, what we know is that the somatic
sensory and somatic motor maps can undergo a fairly dramatic reorganization
across the life span. We used to think that this kind of
plasticity was limited quite stringently by a critical period in early life.
But we now know that it's possible to absorb plasticity in these somatotopic
maps, even into adulthood. And this was shown rather dramatically by
a series of experiments led by Michael Morsnick at the university of California
in San Francisco in the 1980's and then years since then.
And many experiments have led to similar kinds of observations.
And here is an experiment that was done on an owl monkey.
And the experiment involved the surgical removal of a digit in the contralateral
hand following a mapping of the somatic sensory cortex.
And so the question was, how would that somatic sensory cortex change in the
months following the surgical amputation of a digit?
And so, here on the left hand side of this figure, is a map of the hand region
in the somatic sensory cortex in area 3b, adjacent area 1.
And what we see are the territories that contain neurons that were responsive to
stimulation of each of the five digits on the monkey's hand.
Then, following the amputation of digit number 3, what was seen after several
months of recovery, is that the cortical area that responded to the digit number 3
before the surgery has now come to represent the adjacent digits 2 and 4.
So, now this part of the brain seems to have been taken over by circuits that
were either already there in silent, or represented the growth of new synaptic
connections into this region of the hand representation.
Well, I would invite you to refer to an interesting box in the text book, if you
have a copy of the textbook, that considers the phenomena of, of phantom
limbs. phantom sensations generally we now think
are generated at the level of the cerebral cortex.
And it reflects this kind of plasticity that follows injury to a nerve, whether
or not there's actual removal of a body part.
Well, this is a subject that I don't mind telling you that I've come to know quite
a bit about not of my own choosing. But because of a condition that I
developed some years ago that required the surgical removal of a portion of my
right jaw. I'm not sure if you've noticed that I
tend to be a little bit weak here on the right side of my face, maybe just
slightly asymmetrical. It's because the right side of my jaw is
now comprised of titanium and hip bone and in the process of undergoing surgical
interventions for a condition that led me to this state, I've had severe damage to
the mandibular division of the trigeminal nerve.
So, this has led to the experience of phantom sensations around the region of
the right side of my face, and into the oral structures.
And over the years they have changed somewhat, and I suspect they reflect
something like this process that's being outlined here.
Where there is now invasion into a region that has been [UNKNOWN] by this surgery.
And in my case, it reflects the cutaneous surfaces, as well as the oral surfaces,
on the right interior portion of my face. Well, sometimes these phantoms are a bit
distressful. But oftentimes they are somewhat
entertaining, I suppose, so like the man who knew too much in the Hitchcock film
having some information in mind can both be troubling and also at sometimes
somewhat entertaining. Well, enough about me.
let's get back to the subject of cortical plasticity in life, following some kind
of modulation of body structure or function.
Well, one does not have to have amputation or nerve section in order to
induce plasticity in the regions of our sensory and motor maps.
We know this from experimental studies in animals, and now studies in human
subjects where it's possible to relate the relevant map to some particular
experience of the body. And in this case, monkeys were subject to
cortical mapping. In order to represent the distribution of
receptive fields in the somatic sensory cortex as they relate to each of the five
digits on the contralateral hand. And in this case monkeys were trained in
a task that especially activated digits 2 and 3, and to a lesser extent, digit 4.
And after some period of differential stimulation of these digits, what we see
is a fairly significant expansion in the amount of the somatic sensory cortex
that's representing these three stimulated digits.
Perhaps at the expense of the adjacent representations of digits 1 and 5.
So, this is generally the case for all kinds of different sorts of
manipulations. For example, it's been studied in the
somatic sensory and motor maps of violin players.
That typically the right central region of the central sulcus cortex is enlarged
structurally and functionally compared to the corresponding region in the left
hemisphere. And if one considers the act of
practicing the violin, I think we gain some insight as to why that might be the
case. Consider the fingerings of the left hand
along the neck of the violin. It requires incredible skill to
fractionate the movements of the digits of the left hand.
perhaps a qualitatively and quantitatively greater amount of skill
and experience than does it take to bow with the right hand.
If one is playing the instrument in the conventional way.
Well, when the somatic sensory motor maps of these violin players have been
studied, again one sees evidence for an exuberant growth of the corresponding
region in the right central sulcus compared to the left.
Perhaps reflecting the kind of neurobiological change that we see
illustraed in this experimental study using this non human primate model.
Well, what kind of mechanisms then might be responsible for these kinds of changes
in the somatic sencory and motor maps? Well hopefully you will recall the
mechanisms of synaptic plasticity that we discussed in unit 2.
That would include long term potentiation, long term depression, the
consequences of these physiological changes for the growth or the pruning of
synaptic connections. and one might imagine that in this
particular case where we see in it, overall expansion in the dimensions of
the cortical areas that are representing the experienced functions.
We imagine that perhaps long term potentiation has been especially
prominent leading to the growth of new synaptic connections along dendrites.
So, if indeed that has been the case this would occupy more volume, and potentially
account for these larger representations. Well what kind of circuits in the cortex
might actually be responsible for these kinds of synaptic changes that might lead
to an expansion in cortical circuitry volume?
Well I would suggest that one interesting circuit arises from these pyramidal
cells, that we find in the upper layers of the cortex.
Now I will remind you that the thalamic input comes into the middle layers of the
cortex. And then from there these stellate cells
and small pyramidal cells relay information up to cortical layers 2 and
3. And in cortical layers 2 and 3, we see
the computation of new functional properties, but we also see the extension
of long ranging connections that allow for one cortical column to communicate
with nearby columns within the cortical area.
And even to communicate with distant columns in adjacent cortical areas.
So, this computational function of the cortical microcircuit together with the
dissemination. Or the communication of the signals to
other cortical columns is an important function of these pyramidal cells that we
find in the upper layers of the cortex. Well, in studies that my colleagues and I
have done looking at the organization of the cerebral cortex.
We've had occasion to study these long ranging connections that are grown out by
these cortical pyramidal cells in the horizontal dimension.
And the way we've typically studied these connections is by making an injection of
a tracer substance into a local [SOUND] volume of the cerebral cortex above
cortical layer 4. that substance then is taken up by the
neurons that are present at the site of the injection.
And the tracer substances transported along the axons that grow out from these
cells. And what I'd like to show you is some
data from my own lab that, that I generated with the help of my colleagues.
that illustrate this cortical network. So, we're looking at a tracing of axons,
following one such experiment, where, the injection of the tracer was made, right
here in the middle. It's as if we are now looking down upon
the cortex from above. And so, this is where we would find the
cell bodies that have taken up the tracer.
And all of these short line segments that you see represent the axons that have
grown out away from these cells. There is a bit of a halo here in the
middle where I did not trace the axons, because they are simply so dense close to
the cell bodies. It's difficult to differentiate the
labelled axons from the dendrites at that point, so I simply omitted them from this
tracing. And what we see then, is that these axons
extend for several millimeters across the cerebral cortex.
Now, I'll just remind you that each [SOUND] hypercolumn within the cortical
circuit is about a millimeter or so in diameter.
That's probably actually an upper boundary for the size of the human
hypercolumn. We don't quite know precisely what it is,
but it's somewhere a millimeter or less. So, what we see is evidence of
connections that are extending well beyond the typical hypercolumn.
And the implication is that these are connections, that are connecting multiple
hypercolumns together. And so, these connections provide then
for a substratum that potentially might mediate plasticity, in the brain.
Well, let's take a closer look at, these data, I'd like to actually show you what
these cells look like. So, if we were to focus in now on the
region of the injection site, right in the middle, here's what we would see.
This is a dark field photo-micrograph, showing you a cluster of about a dozen or
so neurons, and what we're looking at is mainly the cell bodies, these small
little brown spots and their dendrites, these thick tufts that are proceeding out
from, from these cells. And then these finer thread like
structures, here's one right there, there's another one over here.
These are, these are axons that are extending over some distance across the
cortical mantle. And if we were to look at it in a more
remote site, for example out here what we would see is a terminal cluster.
So, all of these bright little line segments here, these are all portions of
axons, where we have terminals of the axons that arose from cells that were
several hypercolumns removed from the location where we find this terminal
cluster. Now, the anatomy is interesting in and of
itself, but what makes this really fascinating is to relate the anatomy to
the physiology. And we can do this in this particular
study, because we made injections into the visual cortex after we mapped the
distribution of columns that are representing different orientations of
visual stimuli. And what, we, and, actually several other
groups, ahead of us have done in other model systems, is demonstrated that there
is a principle of like connecting to like.
When it comes to these long ranging horizontal connections in the cerebral
cortex. And what I mean by that is that if one
were to inject, let's say a region of the visual cortical map, that has a
preference for near vertical orientations.
What we find is a clustering of connections that has a preference for
overlying other columns that likewise represent near vertical orientations.
And so this now suggests that what we're seeing here is a capacity within this
cortical network to represent different regions of visual space that are
responding preferentially to the same stimulus.
Well, why am I telling you this about these horizontal connections in the
cerebral cortex? It's because this horizontal network very
likely mediates the plastic reorganization of functional maps in
sensory, and motor regions of the cerebral cortex.
we know this from a variety of studies that had looked at how does this
horizontal network in the somatic sensory cortex respond to nerve injury or to
immobilization of a joint that alters the way that musculoskeletal unit can be used
by the animal. And in such instances, we see really a
tremendous amount of exuberant growth, within the cerebral cortex.
involving these kinds of horizontal connections.
And it suggests that there is a dynamical sequence of events that must take place
following the perturbation. that leads to the growth of these
connections. It presumably involves perhaps the
awakening of silent synapses that are already present in this network.
and that might then be followed by the growth of new axonal collaterals that
extend the range and the density of synaptic connections.
Now, we'll say more about the growth of axons in the brain, or lack thereof,
following injury to the brain itself. But at least with injury to peripheral
structures, or to the structured use of the peripheral structures.
We think that this horizontal network is an important mediator of the adaptive
plasticity that can follow in, in the consequence of that kind of disturbance.
