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.
Major Forces In Early Brain Development
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Medical Neuroscience
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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.
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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
Welcome to this tutorial on early brain development.
This topic today will relate to several of our core concepts in the field of
neuroscience. in this session, we're going to talk
about how neurons communicate, but in a different context than what we did in
Neural Two. So, yes, indeed, neurons communicate
using both electrical and chemical signals, but today, we're going to focus
on the earliest events that led to the development of the nervous system, and we
will explore, in some detail, a means of chemical communication that doesn't
involve synapses, but it's cell to cell communication via chemicals nevertheless.
And, it is a mode of signaling that results in the acquisition of cellular
identity, cellular fate, and the regional specification of structure in the
developing brain. I think you'll find that a fascinating
example of how specific molecules can be used to build a brain.
Well, we will also be talking about the expression of specific genes in the the
developing brain. So, in a sense, we can apply actually,
core concept number three, that genetically determined circuits are the
foundation of the nervous system. we will not be talking about the
formation of circuits, in this tutorial, we'll save that for a later one.
But, we will definitely be exploring examples, where the specific expression
of genes is essential for building the foundations of the central nervous
system. And then lastly, I think the core concept
that I'd like to allude to, just briefly as we go through this tutorial, is that
life experiences can change the nervous system, and the kinds of life experiences
that I have in mind here are not the sensory motor experiences that we've been
talking about in the last couple of units of this course, but, rather the
environment that the developing brain might find itself in depending upon
factors such as diet the presence of environmental toxins.
We can think of these as being very early life experiences that can shape the
formation of the brain, unfortunately, often for the worse.
Well, okay, with that as a bit of context, let's look at our learning
objectives for this tutorial. first I want you to be able to
characterize the events that occur during some really important stages of early
embryonic development called gastrulation and neurulation.
I want you to be able to state the significance of neuroinduction.
This is a really important process that I'd like for you to be able to understand
and, and be able to discuss with a friend or a family member as a result of this
tutorial, and neural induction is one of the key mechanisms that leads to the
initial development of the central nervous system.
Thirdly, I'd like to be able to have you discuss the factors that guide the
migration of neuroblasts, which are the primordial cells that will give rise to
the neurons and glia of the brain, and they have to migrate to get to their
final destinations. So, I want you to be able to have some
capacity to discuss how, how that happens, how they migrate through the
developing nervous system. I want you to be able to characterize the
cellular mechanisms that influence the differentiation of neurons and glia.
Obviously, they are distinct type of cells in the nervous system that serve
distinct functions. And in some point in development, cells
need to make a decision about what kind of cell they will become, a neuron or a
glia, and we're beginning to gain some insight as to how that happens.
And then, lastly, in this tutorial, I want you to be able to describe the role
of programmed cell death, we call that apoptosis, and the development of the
central nervous system. Obviously, we have an aggressive and
ambitious agenda for this tutorial, so let's go ahead and get started.
And, I'd like to set the state by talking in very broad terms about what I consider
to be the three major forces that shape the developing brain and I might even
argue that these forces are critical for shaping the evolution of the mammalian
brain, but that's a different topic for a different day.
In the context of development, I want you to consider how these forces interact,
and we will return to this theme as we progress on through our unit on the
changing brain. So, let me introduce these ideas and give
you a sense of what I have in mind here. So, when we think about the factors that
shape the developing brain, I think a lot of us might come quite quickly to the
notion of, well, okay, there's nature and there's nurture.
But, what do we really mean by these terms?
Well, by nature what I mean are, lineage derived signals that reflect the
expression of specific genes. so, these are genetic instructions, or
what I like to call genetic specification.
Okay, so nature reflects the genome that a cell has inherited from its parent cell
and there are specific patterns of gene expression that are responsible for much
of the early formation of the nervous system.
We'll spend a lot of time in this tutorial emphasizing this particular
force in brain development. Well, as the developing nervous system
acquires a functional capacity then other kinds of developmental forces take shape.
Well, we often think about nurture as something that might come a little bit
later in brain development as the developing nervous system acquires the
capacity for sensory experience and motor behavior.
nurture can be thought of as environmental interactions, that is,
experience dependent modulation of brain activity.
There is brain activity going on at later stages in development once synapses begin
to form and that activity is endogenous that is, it isn't necessarily reflecting
the interactions of sensory receptors with stimuli in the environment.
But increasingly, as the brain does develop, and certainly in postnatal life,
a topic we'll come to in a later tutorial, the experience of the infant
becomes an important shaper of ongoing development of the brain.
So, we can think of nurture then, as environmental interactions of the
developing brain, and obviously, when we consider genetics specification in
sensory motor experience, we recognize that these factors interact.
Well, until fairly recently, I probably would have been ready to move on at that
point, but thanks to some wonderful collaborators that I've worked with over
the last few years who come from a very different discipline, my collaborators,
my friends they're actually theoretical physicists, and they've helped me
understand that there's really a third major force in brain development that
biologists ought to confront. And so, I've been happy to be educated
and to really embrace this, this idea, and actually make it part of my research
program. And that is to recognize that self
organization is a very important force that shapes, that developments and the
maturation of circuitry in the central nervous system.
So what do I mean by self-organization? Well, self-organization, reflects the
interactions of one cell to another, or many cells with respect to their
neighborhood environments, and these interactions are mediated via activity
based mechanisms. So, self-organization reflects the
dynamical systems property of the developing brain.
So, as systems form synaptic connections and they acquire the capacity to generate
electrical signals and activity now becomes possible.
Self-organization begins to shape the distribution of synaptic connections and,
and axonal arbors, and the structure, what we call the functional architecture
of neural networks. And I, and I, I've been slow to come to
appreciate this concept because, until fairly recently, it hasn't really been
possible to apply quantitative tools to characterize the organization of
circuitry in the brain. But, now that we can do so, it's
becoming, really quite compelling, I think, that the structure and the form
and the precision of synaptic connections that we see in neural networks, is, is
far greater than what can be accounted for from the genome, from genetic
specification and we've done some experiments.
And others, I think would concur that the degree of specification, of circuitry in
the brain, couldn't possibly be instructed by a sensorimotor experience.
So there must be an additional force, additional factor at play and that
additional factor is self-organization. And so, self organization interacts with
sensorimotor experience, it interacts with, genetically encoded mechanisms, and
together, these 3 forces shape brain development.
Now, as you might imagine, as these forces interact, there's opportunity,
unfortunately, for things to go awry. Well, there are various ways in which
these basic mechanisms of development can go awry in brain development.
There can be mutations of genes that affect how, these genetic instructions
are read out, how the genes are transcribed and how the messenger RNA
molecules are translated into proteins and then how those proteins are actually
processed and inserted where ever there functional role happens to require their
presence. there are also, interactions among cells,
that are mediated via these activity based mechanisms, that are responsible
for self-organizing networks in the brain.
And, well, self-organization seems to be remarkably robust against perturbations.
One can imagine that the self organization of the brain might be forced
into some different, kind of state or some different kind of dynamical system
depending upon the interactions, perhaps, with molecules present in the environment
that might effect how genetic instructions are played out.
And then, lastly, one can imagine that sensory motor experience could be
important in later stages of brain development and indeed, perhaps across
the life-span as the experiences of the body begin to feedback upon the structure
and function of the human brain. And, I think what we've learned from a
variety of, of sources is that sensory motor experience can cut both ways.
It can be beneficial. It can promote the maturation of the
nervous system or it can be detrimental. It can reinforce functional impairment.
Well, these are topics that I want to progressively unfold, but I, I do want to
get them out there in front of you as we begin this consideration of the
development of the nervous system and how the nervous system changes across the
life span. Alright, so, what I'd like to do now is
talk about the early stages of the formation of the nervous system which
will largely reflect the expression of genetic specification in the developing
brain.
