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Summary of all the lectures of MG Drugs of the central nervous system
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Summary of all the lectures of MG Drugs of the central nervous system
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Drugs for the CNSLecture 1 Dolga
Introduction to CNS diseases and their therapies
Katzung ch. 21-32 & slides from lectures & basic principles katzung 1-5, 60, 66
Cyto-architecture and anatomy
Brain development during evolution and during the embryonical phase are important for
understanding the relationship between separate brain structures. These two correspond very well
to each other. The brain consists of cells that are represented by neurons, endothelial cells,
oligodendrocytes and the glia cells which can be astrocytes or microglia.
The function of the nervous system is determined by neural networks that consist of neurons that
communicate with each other via synapses. The electrical signal that is reached in the synapse is to
secrete neurotransmitters from the pre-synaptic to the post-synaptic neuron. The most important
neurotransmitters of the brain are glutamate, a stimulatory neurotransmitter, and GABA, an
inhibitory neurotransmitter. In phsyco-pharmacology, dopamine, norepinephrine and serotonin are
very important.
The brain of the mammals is highly dominated by the cortex. There are two types of cortexes. The
smooth cortex is correlated with lower cognition and is present in e.g. mice. The expanded and
folded cortex is linked to an increase in cognition and more sophisticated functions. The folded
cortex is present in mammals. The closer an animal is to the human following evolution, the bigger
their brain is (the more they look like a human brain).
Elephants and dolphins also show highly expanded and folded cortexes. The expansion of the cortex
is coupled to an increase in complexity of the function, as this is defined by the distinction of the
number of cortical layers. This is mostly due to the emersions of additional association areas which is
very important, because there the information comes from different inputs and these inputs are
integrated. So in an expanded cortex there is an increase in the distinct areas e.g. pre-frontal cortex.
These are the places where the most sophisticated executive functions take place e.g. decision
making and long term planning.
A chimpanzee or gorilla brain is approaching the complexity of the human brain. Their size is still
much smaller than the human brain (gorilla is half and chimpanzee a quarter). To study human the
brain, monkeys are better to use than mice because their brains are more alike humans.
Despite all the similarities there are critical differences between primates and the human brain. The
major functional difference lies in the language and communication.
Animals need their brain to coordinate their movement. Most animals are bilateral symmetric,
meaning that you can divide them in two equal halves but only via one way of division. Sea stars for
example, can be divided into two symmetric halves via many different divisions, making them lateral
symmetric. The animals that are bilateral symmetric have more complex movements than lateral
symmetric animals. So these have to be better coordinated which is done by the brain. So during the
evolution the brain had to evolve to be able to execute all these movements.
To execute all these movements, animals have to integrate the information that is coming from the
sensory nerve and then they have to dictate the muscle to move using motor neurons. The motor
neurons will act according to the information that is provided by the brain.
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, In the primitive brain we can distinguish four different parts.
The spinal cord, hindbrain, midbrain and the forebrain. If you
look in other animals, this similar structure can be seen. Brain
areas that are closer to the spinal cord, have a very vital and
basic function. For example there are centres for the blood
circulation, digestion and for breathing. In the upper part of
the brain (forebrain) we have decision making centres.
In the embryo the same regions can be detected. As we develop, there is a huge structural change.
There is an increased hindbrain, a relatively small midbrain and a huge forebrain.
The cerebral cortex has several lobes. The lobes are separated by the
sulci. These sulci represent the grooves in the cerebral cortex.
Between the sulci we distinguish gyri, which represent the folds or
bumps in the brain. The sulci and gyri make up all the folded surface
of the cerebral cortex in the form of six-layered sheets. Due to the
folding, a much larger area is created in comparison with other
animals. The folded parts of the brain provide more possibilities and
more neurons to be present. The cerebral cortex makes up about 80%
of the brain. This percentage is the same in apes.
The frontal lobe is the frontal part of the brain which has an executing function. This is the boss of
your body and your emotions. If there is injury in the frontal lobe, you will have huge emotional
swings. The parietal lobe processes sensory information and has an association function. The
occipital lobe is located at the back of the skull. Its main function is related to vision. At the lateral
side of the brain is the temporal lobe. This is responsible for language, memory, smell and the
auditory system. There also is a very small insular cortex which is important for taste, pleasure and
feelings.
In the parietal lobe there is a very important area called the
somatosensory cortex. Here, all the information coming from
the sensory neurons is getting integrated. Adjacent to this area,
in the frontal lobe is the motor cortex. This provides
information on how to react.
Main brain compartments:
The brainstem has 3 main parts (from close to far from the spinal cord): the medulla oblongata, the
pons and the midbrain. The closer a structure is to the spinal cord, the more viral the function. So
these areas are crucial for vital body functions such as breathing. The second function of these areas
is to filter and route information that is coming from the sensory neurons that are going to the
cerebral cortex. And also the motor neurons that descend to the muscle once a decision has been
made in the cerebral cortex are filtered and routed here.
2
,The cerebellum (arbor vitae) is located at the back of the brain. It is mainly important in motor
coordination and motor memory. For example, for learning how to ride a bike you need your
cerebellum. But also for you to remember this after years, you need your cerebellum. This brain area
is coordinating voluntary movements. The cerebellum is connected to the brain stem and to the
spinal cord. But is also communicates with the hemispheres of the cerebral cortex.
The left part of the cerebellum will communicate with the left part of the spinal cord and vice versa.
But then the left part of the cerebellum will have connection to the right part of the cerebral cortex.
Cerebellum – spinal cord → same sides communicate with each other.
Cerebellum – cerebral cortex → opposite sides communicate with each other.
There are 3 main structures of the brain important for the voluntary movements. This are the
cerebral cortex, the brainstem and the cerebellum. The motor part is going through the spinal cord.
The thalamus (green) is the brain area where all the information is
sorted. The thalamus also contains the hypothalamus (blue) which is
responsible for thermoregulation and the endocrine system. And the
pituitary gland (red) which is responsible for hormonal activity and
the release of oxytocin and also for the water balance. So the
pituitary gland is responsible for neuroendocrine activity.
The cerebrum is the area where all the information from the sensory part is integrated and also it
makes sense of what we see, hear and emotions. The function of the cerebrum can be studied using
several methods:
1. Structural Magnetic Resonance Imaging (MRI) → used to obtain high resolution images of
the anatomy of the brain. You can measure the size of the cortex or of the grey or white
matter. The grey matter is on the outside and consists of the cell bodies of the neurons,
while the white matter contains the axons which are covered in myelin.
With MRI you can study the activity of certain brain areas during certain activities. You can
also study behaviour. For example when you already expect that you are getting rewarded,
different brain areas are activated compared to when you are actually making effort to get
that reward.
2. Functional MRI (fMRI) → this is allowing us to examine changes in the local blood flow in the
brain. This provides an indirect measure of the brain activity. A change in the brain activity
occurs for example when a person is doing a movement in response to a stimulation.
Ipsilateral hemisphere means the same side. So for example when you are moving your right
hand, it is the activity on the right side of the brain.
Contralateral hemisphere means the opposite side. So when moving your right hand, it is the
activity on the left side of the brain. It can be seen that the brain activity on the contralateral
side is much higher. This is because the information coming from the right part of your body
goes to the left part of the cerebrum.
When now a person has a stroke on the right side, you see that the brain activity especially in
the ipsilateral hemisphere is changed compared to a person that did not have stroke. So after
a stroke, the brain activity especially changes (increases) on the side where the stroke
happened. This may be because it tries to compensate.
Differences can also be seen between man and woman. For example during talking, woman
use both sides of the brain while man only use one side. So there are differences in language
processing between the man and woman.
3
, 3. Diffusion Tensor Imaging (DTI) → to study the white matter. This method is a type of MRI
allowing to measure microscopic movement of water in the brain. DTI can be used to
evaluate the integrity of the white matter in the brain. The white matter allows signals from
one region in the brain to be transferred to another region. One important pathway for this
research is the corticospinal tract. You can see that when a person has a stroke on the right
side of the brain, that the fibres (white matter) are reduced here. You can measure how
intact the axons are. Damage to these tracts causes loss of movement ability.
The cerebral cortex is essential for consciousness (mind). Important parts are the dorsolateral
prefrontal cortex and the medial prefrontal cortex.
The corpus callosum is the brain part full of white matter. So there are a lot of fibres. The corpus
callosum connects the right and left hemisphere with each other. The left hemisphere is more
responsible for cognition and planning while the right hemisphere is more responsible for creative
thinking.
There are 3 main aeras for language processing:
1. Broca’s (B) → related to the initiation and production of speech. This is located in the frontal
lobe. To be able to speak you need this area.
2. Geschwind’s (G) → in the parietal lobe.
3. Wernicke’s (W) → important for understanding of written and spoken language. This is
located in the temporal lobe. When you have a defect in this area, you can speak but you do
not understand the words because they do not have a meaning to you. The vocabulary may
therefore be large in such person, but understanding is not possible anymore.
The W and G area together are important for the creation of a meaningful speech. The B area is
important to produce the vocalisation and also to sense information to the cerebral cortex.
Language related pathways are strongly modified in humans compared to other animals → there is a
projection of the language area to the temporal lobe in humans. Language areas are mainly located
in the left hemisphere.
The basal ganglia is beneath the corpus callosum. It consists of 3 main
parts: caudate (blue), internal capsule (purple) and putamen (red). These
parts are forming the striatum. They are very much responsible for
involuntary movements.
They are very important for specific diseases related to movement
dysfunction e.g. Huntington and Parkinson disease.
This is a coronal section. When now looking at a sagittal section you can
see that the basal ganglia covers quite a big part of the brain.
On top of the basal ganglia is a very important nucleus accumbens. This is taking care of our reward
behaviour, it coordinates addiction behaviour and it is involved in pleasure.
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