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.
Neural Circuits That Govern Sleep and Wakefulness, part 1
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Medical Neuroscience
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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.
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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 REM sleep is really a fascinating state of body and brain.
And let me tell you a little bit about what's going on there.
So yes, it's rapid eye movement sleep but it's so much more than that.
So the cerebral cortex is in this desychronized state.
And electroencephalographically, that is high frequency, low amplitude brain
waves. but when we look at the brain with
imaging methods, we know that there are some really interesting features of blood
flow that suggest that certain parts of the brain actually have increased
activity over resting conditions. Whereas, others had decreased activity.
Specifically, those areas that are increased include structures that are in
the medial parts of the forebrain. Structures associated with the limbic
forebrain, such as the anterior cingulate cortex.
Our medial temporal lobe memory system in the parahippocampal gyrus.
just in front of that, we have the amygdala.
So, as we'll see in a different tutorial, these are all structures that are
intimately associated with the experience and expression of emotion.
[SOUND] And the hyperactivity of these structures during REM sleep very well may
be responsible for the emotionality that seems to be present in so many of our
dreams. Meanwhile, those parts of our brain that
are, otherwise, involved in executive control functions, such as this
dorsolateral prefrontal cortex. These regions actually show decreased
activity relative to the resting state and perhaps with a decrease in the
moderating influence of this executive control network.
This might help explain why sometimes the content of our dreams can be socially
inappropriate. [SOUND].
So, yes indeed, REM sleep [SOUND] is the phase of sleep where most, but not all,
of our dreams, occur. I'll have more to say about dreams in
just a minute. So, as we cycle through our stages of
non-REM sleep and then into REM sleep, it's not just the brain state that's
being modulated, but also the state of the entire body.
So this can be assessed in a variety of means and here are some data that are
fairly typical in terms of what might be gathered during a sleep study if one were
to go to a clinic that's specialized in the treatment of sleep disorder.
Now, these are somewhat idealized data. So most of us don't have such beautiful
looking cycles of non-REM to REM sleep throughout our typical night.
But nevertheless, this shows a typical night sleep where we cycle through
non-REM and REM sleep. we tend to spend increasingly more time
in REM sleep as our night progresses. And then less time in stage four sleep,
and eventually even less in stage three sleep, as we approach waking, time.in REM
sleep as our night progresses. And then less time in stage four sleep
and, eventually, even lessen stage three sleep as we approach waking time,
wherever that happens to be for you. [SOUND].
Now, during these phases of non REM and REM sleep movements of, or body's
muscles, including those visceral muscles that are necessary to sustain life
through sleep, are being modulated. So here what we have is a record of the
electrooculogram, which is indicative of when we are moving our eyes.
And sure enough as we enter rapid eye movement sleep that's where we find an
increase in this electrooculogram activity, indicating rapid movements of
the eyes during REM sleep. Meanwhile this is EMG, or
electromyographic data recorded from a limb muscle and what we see is that, of
course, when we're awake there's a fair amount of activity.
And as we're falling asleep this activity begins to subside.
It begins to pick up again as we pass back three more stages of non-REM sleep
towards REM. But during REM sleep, and this is
especially obvious as we have longer bouts of REM sleep.
There seems to be a supression of muscular activity during REM sleep.
And this is really amazing. it in fact is the case.
So for most of our large skeletal muscles, there is active suppression of
muscle activity during REM sleep. Now some have suggested that this is
adaptive, this is so that we're, we don't act out our dreams with our
musculoskeletal system. that may be the case we don't exactly
know how to interpret this phenomenon. But there is some really fascinating
neuroscience that explains the inhibition of alpha motor neurons that innervate
these large skeletal muscles during REM sleep.
[SOUND] I'm wondering if you can hear that.
The barred owls in the woods behind me are starting to go crazy over something.
I don't know exactly what's going on there but hopefully they'll calm down.
Now notice what's going on in our visceral motor system.
So while we are phasing into our deeper states of non REM sleep, our heart
rhythms are subsiding, so are our respirations.
But as we begin to cycle towards that paradoxical sleep that REM sleep, there's
an increase in both heart rate, and our breathing rhythms.
And so again this is perhaps consistent with activation with of the limbic
forebrain, consistent with a heightened sense of emotionality.
and then also for men men experience penile erection during sleep and women
experience an increase in vaginal lubrication during sleep.
Again, perhaps, consistent with an increase in activity coming out of the
limbic forebrain, which is also highly engaged in various kinds of, of sexual
behaviors, as well. So just a couple of other interesting
points about REM sleep that are worth making.
While sleep is necessary for life it appears as though REM sleep might not be
necessary. As I mentioned earlier, when we were
thinking together through some of those opening questions, there are individuals
that are taking medications that suppress the experience of REM sleep.
That would be a side effect of their medication.
And these individuals seem to be getting along quite well.
their lives are not in jeopardy. At least not because of the cessation of
REM sleep. Now, it may not be so clear why we have
REM sleep. But most of our dreams happen during REM
sleep. And so perhaps that's providing us some
insight that maybe what's really important about REM sleep is the
opportunity to dream. this is idea, an idea that's been with us
for some time, and it's regaining traction with some new neurobiological
studies that are being done to try to explore the possible benefits of
dreaming. So while REM per se is still quite
mysterious in its significance, biologically speaking.
perhaps it's at least providing a space for the experience of dreaming, which,
we'll, we'll turn to in just a moment. So as Hamlet said in his famous to be or
not to be soliloquy to sleep, perchance to dream.
So Many of us, like Hamlet have, have
wondered about dreaming and what it might actually be doing for us.
And of course many over the last 150 years or so have argued vigorously about
this. certainly Sigmund Freud had his ideas
about the importance of dreams. Freud argued that dreams provided a means
for the ego to relax its grip on the id. now, now most of us don't really adhere
to these Freudian concepts. we want to replace them with
neurobiological concepts. And so, we're not quite sure what to do
with this one. But there may be a sense that Freud was
ahead of his time, at least anticipating some of the brain mechanisms that reflect
a difference between explicit processing in the, in the brain and implicit
processing. Well, there's an idea that says dreams
are really an opportunity to rehearse some of the less common behaviors that
are not often expressed in the waking state.
For example, very intense emotional states perhaps aggression.
So various kinds of behaviors that might be risky and self-destructive if they
were to occur during wakefulness might be played out vicariously through dreams.
[SOUND]. Well, there's another idea It says that a
dream is an opportunity to unlearn, that is to erase some kind of non-adaptive
pattern of neurological activity, perhaps stored as a memory.
So this could be a very useful mechanism for us to get rid of unwanted memories.
Well, there's another thought that seems to be gathering a lot of interest these
days, which is exactly contrary to this last one.
Rather than dreaming being about unlearning, the prevailing view, I think,
among neuroscientists today, is that dreaming, in fact, provides an
opportunity for synaptic plasticity. That dreaming provides us with
opportunity to consolidate memories, to engage mechanisms of synaptic plasticity,
and retain the learning of the day. So there are a variety of studies that
are showing evidence for this view from behavioral studies to neurophysiological
studies. And it's quite exciting to see this
emerged as, potentially, a neurobiological mechanism that explains
the benefit of dream. Now there's so much yet to be discovered
about this. We are far from understanding exactly
what's going on here. But it's an intriguing concept that
dreaming provides us an opportunity to actually consolidate the learning of the
day. Well, there are still some nihilists out
there that would say that dreaming is nothing by an epiphenomenon.
That perhaps actually REM sleep is important after all.
We just don't understand why it's important yet.
But dreams per se, may just be epiphenomenal.
Well, I think the sum of all this is that no one really knows why we dream or even
how we dream, but we are developing some concepts that I think maybe are leading
us down a fruitful path. So, let's see where this goes over the
next decade or so. And, hopefully, we'll have much greater
insight into both the nature of dreams as well as the neurobiological mechanisms
underlying dreams. Well, it's to some of those mechanisms
that we do understand that I want to turn to now.
So, let's consider some of the neural circuits that are important in governing
sleep. So, as should be clear to you by now
sleep involves a series of transitions. From one, state of body and brain to
another. And this reflects a complex interplay
among a variety of neurochemical systems that are present in the hypothalamus and
the reticular formation of the brain stem.
And these are systems that have widespread projections that can effect
circuitry really throughout the central nervous system, even down into the spinal
cord. But they are especially focused on
modulating the way the thalamus interacts with the cerebral cortex.
So I'm going to give you a bit of a detailed run-through, these mechanisms,
and then we'll come back and talk about them in slightly broader brush strokes.
So what I'd like to do is go through this table and lay out for you some of the
details about which neurochemical systems are involved in which brain states.
And then we'll come back and, and talk about how they interact with one another.
So, first let's consider the maintenance of wakefulness.
So, wakefulness is a prodcut of the activation of quite a large number of
neurochemical systems. Among the most important is are the first
two listed here in the chart, cholinergic nuclei that are found near the junction
of the pons and the midbrain, and the locus coeruleus.
The locus coeruleus is a collection of cells in the dorsal [UNKNOWN] to the pons
that produce the neurotransmitter norepinephrine.
So together, these two, acetylcholine and norepinephrine, very important
neurotransmitters in maintaining wakefulness and maintaining vigilance.
But in addition to acetylcholine and norepinephrine, we also have other
neurotransmitters. The serotonin system, which are derived
from the midline raphe nuclei that are found right in the seam of the brain
stem. Raphe meaning seen.
There's an important nucleus in the posterior hypothalamus called the
tuberomammillary nucleus. This nucleus produces histamine.
And histamine, when it's active, promotes wakefulness.
The lateral hypothalamus is home to collections of cells that produce a
variety of peptide neurotransmitters. One of them is this peptide called
orexin, sometimes called hypocretin. And orexin, when active promotes
wakefulness mainly by stimulating these tuberohypothalamic cells, that then
release histamine. But orexin has other roles to play in
other circuits that project out of this lateral hypothalamus.
So these are systems that promote wakefulness.
The systems that then promote falling asleep feeling drowsy involve basically a
decrease in the activity of many of the ones that I've just mentioned.
So the functions of acetylcholine, or norepinephrine, of serotonin, they're all
decreasing as we are entering the stages of non-REM sleep.
So we're going to talk a little bit about the neurochemistry, as to what's pushing
these systems that we're active in the waking state towards decreased activity
in non-REM sleep. Well, this leaves us then with a
consideration of the neurochemistry of REM sleep.
Now in REM sleep, we have a bit of a hybrid state, where the brain is active,
the body is in this suppressed partially paralyzed condition.
And this dichotomy between an active brain but an inactive body and yet being
asleep implies that there must be some differentiation of neurochemical systems.
Some of which might be turned on, some of which might be turned off.
And indeed that seems to be the case. The cholinergic nuclei of this junctional
region between the pons and the midbrain, are active.
In fact, in a quite unusual pattern of activity that produces a very discrete
type of electrical signature that propagates from the pons into the lateral
geniculate nucleus of the thalamus, and then into the occipital cortex.
These are called Pontogeniculooccipital waves, or PGO waves.
So there's a very distinct pattern of activity that's present in these brain
stem cholinergic neurons. Meanwhile, some of the other amine
neurotransmitter systems that otherwise might support a more wakeful condition
are inactive. This would include our norepinephrine
system and then the endolamine system involving the neurotransmitter serotonin.
So both serotonin and norepinephrine are depressed at the same time that the
cholinergic system is turned on in this very peculiar way.
So, there are a variety of mechanisms then that are operating, some of which
are being pushed up, some of which are being pushed down.
That help explain these very peculiar transitions that we have in our state of
body and brain. Well, I'll give you a bit of an
anatomical view of some of these systems now.
So, our cholinergic nuclei that are so important in maintaining wakefulness and
then are turned on during REM sleep. Are found here in the rostral pons and in
the caudal midbrain. And these neurons have projections that
are directed up towards the thalamus. They also have some projections down
towards other parts of the reticular formation in the medulla.
Our raphe nuclei are found along the midline of the brain stem from the
midbrain all the way down into the medulla.
And these raphe nuclei give rise to very long projections, that basically extend
all over the entire brain, and even down into the spinal cord, where they release
serotonin. The tuberomammillary nucleus is a very
small nucleus in the posterior part of the hypothalamus and it gives rise to
projections that extend throughout the entire central nervous system.
And these projections release histamine and this histamine is an important,
neurotransmitter in supporting the wakeful active brain.
And as many of you who have seasonal allergies know, if you take an
antihistamine you are very likely to feel drowsy.
And that is because you are antagonizing this natural wakeful promoting chemical
in the brain. And finally, we have this beautiful
structure found along the dorsal tegmentum of the pons called the locus
coeruleus. And this is the location of the cell
bodies that produce norepinephrine. And norepinephrine is right up there with
acetylcholene and histamine, as being among the important neurotranmitters that
support wakefulness. these neuronordic fibers extend
throughout the central nervous system, releasing norepinephrine and modulating
our level of arousal, vigilance, and attention.
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