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.
Reward and Addiction, part 1
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Del curso dictado por Duke University
Medical Neuroscience
1042 calificaciones
De la lección
Complex Brain Functions: Sleep, Emotion and Addiction
In this concluding module of Medical Neuroscience, we will consider the neurobiology of sleep and the neurobiology of emotion, including addiction. Both topics involve explorations of complex, widely distributed systems in the forebrain and brainstem that modulate states of body and brain.
Conoce a los instructores
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
In today's tutorial, which is, as you know, the concluding tutorial of, unit
six. On complex brain functions, and indeed
the concluding tutorial of medical neuroscience.
I've chosen to wrap up the course with a topic that is of tremendous importance
for anyone entering the world of healthcare.
Because of the impact of addiction on societies all over the world.
And indeed because of the risk of addiction for workers in the healthcare
Sector of our global economies where opportunity and risk abound.
So I want us to just think together, very briefly, about some of the mechanisms of
addiction that pertain to the structure and function of the limbic forebrain, and
to do so we're going to back up just a little bit And, talk briefly about the
basal ganglia, and the brain's intrinsic system for reward.
So, today's session pertains to several of our core concepts in the field of
neuroscience. We will, again, talk about the complexity
of the brain, and illustrate the fact that the brain is, indeed, the body's
most complex organ. We'll be talking about genetically
determined systems, and circuits, that provide the foundation for the function
and operation of the central nervous system.
And in this case, we'll be focusing on the brain system for reward.
And then lastly, the phenomenon of addiction is a sad but compelling
demonstration of how life experiences can change the nervous system.
And the challenge for medical science and for rehabilitation professionals is to
understand best, how do these intrinsic systems of reward operate in the brain?
And how might we best approach the process of undoing the grip of addiction,
that can come upon the brain's intrinsic reward system?
So my learning objectives for you, in this tutorial our first to be able to
discuss the brain's reward system and next to discuss the involvement of the
limbic fore brain in mediating addictive behavior.
Now, as we get into this topic, it will be clear that one very important brain
system. That is germaine for understanding
addiction is in fact a component of a brain system that we've already spent a
fair bit of time wrestling with. And that is the basal ganglia.
So I'll remind you that there are multiple streams, or loops, as we
sometimes call them that run through the basal ganglia.
We talked about a dorsal motor stream, or a motor loop, that principally runs
through the dorsal parts of the basal ganglia, that is the putamen which is a
major component of the striatum, lateral to the internal capsule.
The putamen has important connections to the globus pallidus which then projects
to the motor thalamus that modulates The expression of movement, specifically the
initiation of movement or the suppression of movement.
We talk briefly about a cognitive stream that runs through the caudate division of
the stratium, the caudate nucleus. And this caudate nucleus has projections
into the Pars reticulata component of the substantia nigra.
That's a palatal region that serves the anterior part of the head of the caudate
nucleus, and it's involved in this cognitive loop that involves movements of
the eyes, as well as movements of the mind.
As I've mentioned several times, what we look at is often what we are thinking
about. And, that can become the object of our
plans for future actions. Now, in this tutorial we're going to
focus on the third major division of the striatum, the Nucleus accumbens, which is
an important component of what we've called the Ventral striatum.
And this ventral striatum has the same kind of circuitry that we've seen in the
other divisions that is a direct and an indirect pathway.
But it's operating upon inputs that are coming from different parts of the
telencephalon. And the output from the palatable
component of this striatal loop is directed towards a non-motor thalamic
nucleus namely the mediodorsal nucleus of the thalamus which then projects into our
prefrontal cortical networks. So let's take a closer look at this
ventral-limbic loop in the basal ganglia. And that will help us understand a little
bit more about how our reward system might be operating in the human brain.
So as we see this limbic loop really begins with inputs that are derived from.
Regions of the telencephalon such as the amygdala, the hippocampus, the orbital
frontal portion of the prefrontal cortex, the cingulate gyrus and even the cortex
at the anterior pole of the temporal lobe These are all important integrative
associational areas, that are involved in the experience of emotion.
And the integration of emotional experience with other dimensions of
cognition. So these are the sources of telencephalic
input into the ventral striatum. And specifically what we're talking about
here is the major component of the ventral striatum is the nucleus
accumbens. You'll recall that this is the division
of the striatum that is continuous with the caudate nucleus dorsally and medially
and with the putamen laterally and dorsally.
And this nucleus accumbens wraps right underneath the white matter of the
internal capsule. So here's the internal capsule, and we
see that on either side of the internal capsule are components of the striatum
caudate medially, putanum laterally. And then inferior to this internal
capsule's where we find This nucleus accumbens.
Now, the nucleus accumbens, the ventral striatum, then sends inhibitory
projections into the pallidum. And the pallidum that we have in mind
with our ventral limbic loop is called the ventral pallidum as well as the
reticula component of the substantia nigra.
So the ventral pallidum is a region just behind this section, we can't see it in
this view. It's a region Posterior to the nucleus
accumbens, but inferior to the globus pallidus, so it's a much looser organized
reticulated network of pallidal neurons. While the output from this ventral
pallidum and this particular component of the pars reticulata is directed at that
medial dorsal nucleus of the thalamus. Which is the principal thalamic nucleus
that projects out to the prefrontal cortex.
So the projections here are indeed directed back towards many of the same
Cortical regions that gave rise to input to this nucleus accumbens in the first
place. Most importantly, the orbital and medial
part of the prefrontal cortex. Now what we've illustrated here is the
direct pathway through the ventral limbic loop.
And I hope you've recognized that based on the presence of these two inhibitory
connections within the basal ganglia circuitry, that when active serve the
purpose of disinhibiting the thalamic projection to the cortex, and that
disinhibition then provides a kind of a go signal.
For the engagement of the cortical circuits that are responsible for some
kind of shift in behaviors. So exactly what kind of behaviors we have
in mind is going to depend on what is actually being integrated in this
cortical network at the time. But we can imagine that that has
something to do with affect, with emotion- With mood.
Perhaps even the kind of shift in affect that we would associate with the presence
or the prediction of a reward. That is, we know something good's about
to happen, and there's some kind of a shift in our emotional set.
And, it's that shift played out in this circuitry of the orbital medial
prefrontal cortex, that we think is really the instantiation of a rewarding
experience. Now, in talking about reward we imagine
that there is some kind of operation like this that operates For the instansiation
of the negative valence that we might associate with this kind of behavior.
That is with punishment. Something that has a negative
reinforcement property. Also involves a shift of some sorts.
So we imagine there's likely to be A different kind of network.
probably also in the orbital and medial prefrontal cortex.
But maybe in a slightly different location that is responsible for
initiating that shift towards the negative valence of punishment or
deterrence. Or this Concept that, okay this is a bad
outcome, so I need to learn my lesson here and try to avoid this kind of
contingency in the future. So hopefully this gives you a sense of
how the basal ganglia might actually be key And understanding how the reward
system of the brain might work. To either reward with a positive
reinforcer, or a negative punisher. Now there's one critical component of
this circuitry that I need to highlight before we move on.
And that is found right here, on the medial edge of the substantia nigra in
the mid brain. This is the ventral tegmental area which
is critically important in modulating. The way the circuitry through the ventral
loop of the basal ganglia operate. So the ventral tegmental area is the
source of dopamine for the ventral part of the striatum.
So there are projections from this mid-brain region into the nucleus
accumbens. Where dopamine is released.
And there are a variety of dopamine receptors.
We've tried to keep it simple and only primarily talk about two kinds of
dopamine receptors. In the striatum we have D1 and D2
receptors. The d1 receptors are associated with the
direct pathway so in the illustration that we have, here to the left we imagine
that the D1 receptors are being activated, when ventral tegmental neurons
begin to fire and release dopamine Effecting this direct pathway from
ventral striatum to ventral pallidum. substantial nigra, pars reticulata and
then back to the medial dorsal nucleus of the thalamus.
But there is also an indirect pathway not illustrated here for simplicity, where
dopamine is going to interast with D2 receptors and suppress the firing of
those indirect pathway striatal neuron. And together when dopamine is present the
D1 and D2 receptors work synergistically in order to facilitate the activation of
the thalamocortical connection.
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