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.
Hebb's Postulate
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Medical Neuroscience
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Neural Signaling: Synaptic Transmission and Synaptic Plasticity
Let’s continue our studies of neural signaling by learning about what happens at synaptic junctions, where the terminal ending of one neuron meets a complementary process of another excitable cell.
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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
Well now, we come to the final of our three tutorials on synaptic plasticity,
and in this session I would like to talk to you about Hebb's postulate.
Again we are talking about content that pertains to 3 of our core concepts in the
field of neuroscience. We continue to talk about how neurons
communicate through electrical and chemical signals and we're elaborating on
a new theme for us and that is how life experiences Can change the structure and
function of the nervous system. And as I've commented on in the previous
two tutorials, I think this is a tremendously important and exciting field
within neuroscience because what we are now capable of discovering are the very
mechanisms that we can harness and use to promote healthy living and the treatment
of disease and the rehabilitation from neurological dysfunction and disability.
Well, my learning objectives for you in this session are again to relate.
Our discussion to general cellular mechanisms of synaptic change.
And I want you to be able to state Hebb's postulate and discuss its relevance for
neural plasticity. Ok, we've gone through this a few times
already and we'll do it again very briefly just to remind you of our cellular
mechanisms of synaptic plasticity. Well, this begins with neural activity,
triggering the activation of postsynaptic second messenger systems.
The trigger is typically an alteration in the level of intracellular calcium that's
free in the pseudoplasm of the postsynaptic process.
That is critically important because The amount of calcium in that intracellular
process is going to activate calcium dependent second messenger systems.
And these second messenger systems generally alter two categories of enzymes
that are present within the postsynaptic cell.
Either protein kinases. Which tend to turn on target proteins
through phosphorylation. Or protein phosphatases.
That tend to inactivate target proteins through dephosphorylation.
So this alteration in protein phosphorylation is very important in
mediating the early stages of long term plasticity.
Because what is happening here doesn't involve the generation of new proteins,
just the alteration in the structural and functional competency of existing
proteins. But to get to the long-term stages of
synaptic plasticity, There needs to be a means for altering gene expression.
Though that, so that's the basic scenario by which synaptic plasticity has both
short- and long-term consequences on the structure and function of neuronal
connections. So now, I want us to consider a very
powerful postulate that's been with us in the field of neuroscience for, well, more
than 60 years now. But it's been especially in the last 20 to
30 years that this postulate has really proved to be formative in understanding
cellular and synaptic mechanisms of synaptic change.
Well, this is a postulate that was proposed by the Canadian psychologist
Donald, Donald Hebb, who passed away in 1985.
And the usual form of this postulate that is often reproduced and quoted is from a
very important work of Dr. Hebb's, Published in 1949 called, The
Organization of Behavior. And I know many of you will be interested
to learn about Donald Hebb than I'll have to say and, there's some excellent
compilation of information found in Wikipedia.
I don't normally recommend Wikipedia but, This is a good starting place for someone
just trying to gather some resources concerning the life and the work of Donald
Hebb. Well, that brings us to the principles of
the postulate. What Hebb's postulate stated in principle,
I'm not going to give you the verbatim text, but in principle Is that
coordination of activity or coordinated activity of a presynaptic terminal and a
postsynaptic cell would lead to the strengthening of that synaptic connection
between them. And conversely, uncoordinated activity
between synaptic partners would weaken their synaptic connections.
Now, a colleague of mine from Duke University who, who sadly was take far too
early and with great heartache for, for his family and his friends who, who knew
him well Dr. Larry Catz.
Dr. Catz Encapsulated these principles quite
insightfully as he was known to do in the following phrase.
Neurons that fire together, wire together. The firing together captures beautifully
the heavier notion of coordinated activity and the wiring together speaks powerfully
about the consequences of coordinated activity.
For not only synaptic strength but also the long term consequences that require
the building up of new synaptic connections.
Now Hebb's postulate really is not a departure from what we've been talking
about so far in our tutorials on synaptic plasticity.
The changes in synaptic strength that Hebb could only imagine in his day and now we
come to speak of in these terms are long-term potentiation and long-term
depression. So LTP and LTD would be the logical
consequences of the coordination or incoordination of activity that Hebb
postulated. Now, how does spike-timing dependent
plasticity fit in? Well again, spike-timing dependent
plasticity explains how Synaptic change can occur one post-synaptic spike at a
time under normal physiological conditions that are found in real neural networks
with ongoing activity. So spike timing dependent plasticity has
been a framework that has been based upon data Such as what we've seen previously
here reproduced in figure 8.18. Here in this figure, we see that when
pre-synaptic activity comes before post-synaptic activity, within a fairly
short interval of about 20 milliseconds or so, then we see long term potentiation.
So pre before post leads to long term potentiation.
Conversely, if we see postsynaptic activity presumably driven by some other
input to a neuron than the one that we have command of, when that postsynaptic
activity comes before. Presynaptic activity then that's a regime
that favors long-term depression. So now, to put these data in the context
of heavy inplasticity or Hebb's postulate, we might say that pre before a post is
equivalent to the kind of coordination of firing across a synaptic connection that
would be consistent with the strengthening of that connection.
Where as the post before pre regime, might be a picture of what in-coordination of
activity might mean. At least for the synaptic connection under
study. Presumably there's coordination at some of
the other synapses to this postsynaptic neuron, otherwise it wouldn't be firing an
action potential. But in this particular isolated synapse
that's under study here, it doesn't appear as though.
The presynaptic element is really what's driving the activity of that postsynaptic
neuron. Hence the incoordination, at least at that
one synaptic junction. Okay.
So, again, Hebb's Postulate Is captured by this phrase neurons that fire together
wired together. And understanding plasticity at this level
begins to take us from one synapse to the compounding impact across an entire set of
connections that builds up neural circuits and even neural systems.
So again, change at the synaptic level can produce change in wiring patterns of
entire neural circuits. This is why I love this phrase from Larry
about wiring together. Because it really points to the long term
and broader consequences. Of a change in activity that occurs at the
synaptic level. And so, this synaptic change accumulates
throughout a network of interconnected neurons, and the net effect of firing or
misfiring Maybe wholesale change in the structure and function of network
properties. Well, this is the briefest of our
tutorials that I prepared for you so far. But only in terms of my participation with
you here. I hope that this tutorial continues in the
discussion forum, as you consider the study question that I will leave you with.
And it's a question that is reproduced for you at the, The bottom of your tutorial.
As I've been mentioning, my former colleague here at Duke, Dr.
Larry Katz, proposed the aphorism neurons that fire together, wire together.
Well, this is a wonderful phrase to take away from this tutorial and perhaps it
sounds familiar to an aphorism that you may know, that aphorism is use it or lose
it. And this might appear to be a valid
restatement of Hebb's Postulate, but this is the question I want you to consider and
perhaps even kick it into the discussion forum and share your thoughts about it.
So, here's my question that I leave you with today.
Is use it or use it an accurate expression that reflects a synaptic mechanisms of
neural plasticity? Maybe you have a definitive yes or no, or
maybe you have a definitive no one knows. So go ahead and think about it and, let's
see what kind of discussion we can generate around this question.
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