Functional Anatomy and Neurotransmitters

Question 1

How many regions can the brain be divided into anatomically?

Answer 1

3
- Brain Stem
- Cerebellum
- Forebrain (Diencephalon, Cerebrum)

Question 2

What are the cavities within the brain (the ventricles) filled with?

Answer 2

Cerebrospinal fluid

Question 3

Why is the brain stem referred to as the ‘relay centre’?

Answer 3

All the information that comes from the body into the spinal cord will go via the brain stem before it goes up into the higher centres of the brain and likewise anything from the higher centres of the brain going into the spinal cord and onto the body, will go via the brain stem.

This isn’t a passive process, and this is where initial processing takes place. With most processes there are synapses present, indicating where neural integration takes place, and starts to process the signals that are going through the brain stem.

Question 4

What is the reticular formation (RF)?

Answer 4

It is a network of neurons throughout the brainstem.

The reticular formation receives all the sensory information that is coming from the periphery.

The reticular formation starts to integrate (start make sense) of the sensory information coming in. An important part of this is being able to ‘filter’ un-necessary information.

RF is also important in consciousness and arousal (wakefulness). Reticular activating system.

Brainstem is responsible for reflexes involved in balance and posture.

The brainstem is also the site of exit for most cranial nerves.

Question 5

What is the brainstem further sub divided into?

Answer 5

• Medulla oblongata
• Pons
• Midbrain

Question 6

What is the Medulla Oblongata involved in?

Answer 6

• It is important in involuntary function
• It contains vital reflex centres which are important in for example, control of breathing, circulation, digestion etc.
• For example, the respiratory control centre is within the medulla oblongata, which is important in initiating breathing
• There are also non-vital reflex centres within t he medulla oblongata. For example mediating or cough reflex. It is also where we find the chemoreceptor trigger zone - CTZ, which when stimulated causes vomiting.

Question 7

What does the midbrain contain that is important in Parkinson’s Disease?

Answer 7

The midbrain contains the substantia nigra which is important in the pathophysiology of Parkinson’s Disease.

Question 8

What is the Cerebellum and what is it involved in?

Answer 8

• The Cerebellum is attached to the brain stem, located at the back of the brain
• It is involved in the fine control of movement - which is the execution of coordinated voluntary movement

Involved in integrating lots of information:
- It takes in all the sensory information from the muscles, joints, skin, eyes and eras etc. All that information goes into the cerebellum, which enables us to know about the position of the body.

• The cerebellum is also involved in the planning and initiation of movement. So as well as taking information in from the motor areas, it gives information out to the motor areas which is involved in initiation of movement via the motor areas.
• Procedural memory: When we learn something to do with movement e.g. dance, at first were not really good at that and we need to think about it, but when the time comes we know the dance and can do it subconsciously and able to remember the dance without thinking. This is known as procedural memory, which is important in the co-ordination of subconscious motor tasks.
• The cerebellum is also involved in balance and eye movement.

Question 9

The diencephalon is made up of what 2 components?

Answer 9

1. Thalamus
2. Hypothalamus

Question 10

What is the thalamus involved in?

Answer 10

• The thalamus is located directly above the midbrain
• The thalamus is referred to as the relay centre as all sensory pathways pass through the thalamus.
• Processes such as filtering unwanted information and directing of signals to the correct locations goes on here. This allows direct attention to things that are important and allows us to ignore things that are not important.
• The thalamus also has a role in motor control.

Question 11

What is the hypothalamus involved in?

Answer 11

• The hypothalamus is the major homeostatic control centre
• The hypothalamus integrates all the information that comes from the body that relates to homeostasis - such as heart rate, blood pressure, oxygen in the blood etc.
• All this sensory information is going into the hypothalamus so it can make sense of the information and regulate responses accordingly. This involves regulating the autonomic nervous system and the endocrine system to mediate responses according to the homeostatic changed.
• For example the control of body temperature within the hypothalamus, it measures the temperature of the blood and then will mediate responses, such as if body temp goes down, it’ll mediate vasoconstriction, shivering etc. whereas if the body temp goes up, it’ll mediate vasodilation.
• The hypothalamus is joined to the pituitary gland, which is the master controller of the endocrine system. Hence the hypothalamus is important in the release of hormones from the pituitary gland.
• Hypothalamus forms part of the limbic system, which is important in emotions, behavioural patterns and memory.
• The hypothalamus is also involved in the sleep/wake cycle.

Question 12

What is the Limbic System?

Answer 12

The limbic system is an interconnecting group of structures within the forebrain.

• It includes the thalamus and hypothalamus.

The hippocampus is also associated with the limbic system which is important in memory.

• The Limbic System is associated with basic emotions (fear, anger, anxiety, pleasure, satisfaction etc.). These are basic emotions which are programmed via the limbic system - important for survival.

Question 13

The limbic system mediated the neural centres controlling basic behaviours/responses. What do these include?

Answer 13

1. Preparing for attack/defence, laughing, crying etc.
2. Survival - Eating, drinking, sexual behaviour (reward pathways (done something important for our survival that feels good and want to do them again)) and motivation (to continue to do them).
3. Punishment pathways (things to avoid)
4. Olfaction (smell) - our sense of smell plugs straight into the limbic system, which is why smell is associated with basic emotions.

Question 14

What is the cerebrum and what is it involved in?

Answer 14

The cerebrum is divided into 2 parts:
- The cerebrum cortex
- The basal nuclei (basal ganglia)

The basal nuclei are a collection of neuronal cell bodies. It includes the striatum (caudate nucleus, putamen and separating structure) and globus pallidus.

The basal nuclei also includes the substantia nigra and the subthalamic nuclei (found in the brainstem).

The basal nuclei is involved in the control of movement - referred to as the extrapyramidal motor system. Hence involved in:
1. Modulation of motor activity (generally an inhibitory role)

2. Inhibition of muscle tone (stop the muscles from being contracted)
3. Purposeful vs unwanted movement
4. Posture/support (co-ordination of sustained contractions)

Question 15

What is the cerebral cortex and what is it involved in? Talk about the functional anatomy

Answer 15

• The cerebral cortex is made up of 2 hemispheres (left and right hemisphere)
• The cerebral cortex consists of a shell of grey matter, which is a thin layer around the outside and this is made up of cell bodies and dendrites of the neurons and glia cells. This is where synapses are present hence where all the processing takes place.
• Beneath this is the white matter, and the white matter is made up of axons and they’re formed into tracts, which takes information from one park of the brain to another.
• The cerebral cortex is highly convoluted - consist of peaks (gyri) and trophs (sulci)
• These convulsions increase the surface area of the grey matter and it enables it to have more grey matter on the outside of the brain. The greater the surface area, the greater the amount of processing that can take place.
• In relation to the info coming into or going out of the brain, the hemispheres are controlling the opposite side of the body. For example the left hemisphere is controlling movement of the right side of the body and vice versa.
• It is important that the two hemispheres are able to communicate and this occurs by the fibre tract that goes between the 2 hemispheres, which is called the Corpus Callosum.
• The hemispheres are not completely symmetrical in structure nor equivalent in function. One side of the brain related to the other side of the body. Also some functions are only on one side of the brain such as language (usually left side).
• The functions of the Cerebral Cortex is concerned with “higher functions” including sensory analysis and perception, motor initiation (voluntary) and coordination, conscious thought, language and intellect.

Question 16

Why is the white matter white in colour?

Answer 16

They are white in colour because the axons are myelinated and this myelination causes it to have this white colour.

Question 17

The amount of convulsions is proportional to what?

Answer 17

The amount of convulsions is proportional to the complexity of the organism.

Question 18

Anatomically the Cortex is separated into 4 different lobes. What are these lobes called and what are their functions?

Answer 18

1. Occipital Lobe
   - Is important in vision and it contains the visual cortex. The primary visual cortex is where the information from the eye (the retina) is taken into the brain and where visual processing takes place.
   - Located next to that is the secondary visual cortex, which is where further processing of this information takes place.
2. Temporal Lobe
   - Is where the auditory cortex is located.
   - We have the primary auditory cortex and this is surrounded by the secondary auditory cortex whether further processing takes place.
3. Parietal Lobe
   - Where all the sensory information from the body is processed and consists of the primary somatosensory cortex and the association (secondary) are right behind it.
4. Frontal Lobe
   - Mostly associated with motor function
   - Where the primary motor cortex is present and that is right next to the pre motor area which is involved in planning and initiating movement.
   - At the front is the pre frontal area, where thinking takes place, hence decision making and intellect.
   - It is also where our personality resides. If this is damaged it can change our personality.
   - Also consists of the Broca’s area (motor speech area).

Question 19

What is the somatosensory cortex?

Answer 19

The somatosensory cortex analyses inputs from mechanoreceptors (touch etc.), thermoreceptors (detecting heat and cold) and nociceptors (pain) in the skin, muscle, joints and internal organs.

• All the information from all the receptors go up via the brainstem, through the thalamus and up into the somatosensory cortex where most of the analysis takes place.
• The sensory cortex receives information from receptors on the opposite side of the body
• The sensory receptors from each area go into very specific parts of the body.
• The size of that area is proportional to the amount of input, hence however sensitive that particular part of the body, is due to the greater area of the brain that is devoted to it.
• The area of the cortex devoted to each area of the body is proportional to the amount of information received from that area.
• From the somatosensory cortex, information passes to “association areas” where further processing occurs, before combining with other sensory input and then information from past experience - analysis, integration, perception (enables us to take in all that information and understand that information within the context of our previous experiences).

Question 20

What does ‘plasticity’ mean?

Answer 20

Plasticity meaning that if things change within the sensory input, the somatosensory cortex can change accordingly hence it is use-dependent. So if one area receives extra stimulation or reduced stimulation, the size of the area devoted to this will change accordingly.

Question 21

What is the motor cortex?

Answer 21

The motor cortex is responsible for voluntary movement.

It is located in the frontal lobe

Most of the remainder of the pre-frontal cortex is involved in processing motor information.

The motor cortex sends signals to the alpha-motor neurons.

Question 22

Which cortical areas are involved in language?

Answer 22

1. Broca’s area - Involves the articulation of speech (controls muscles - via motor cortex - for speaking) - controls muscles that are important for speaking
2. Wernicke’s area - Involves comprehension and planning/coherence of language

Question 23

What are glial cells?

Answer 23

The main cell type of the CNS along with neurons.

There are 4 types:
1. Astrocytes
2. Microglia
3. Oligodendrocytes
4. Ependymal cells

Question 24

What are astrocytes?

Answer 24

• They are large star shaped cells and are the most abundant glial cells of the CNS
• They have a dynamic role - they communicate with each other and theres a network of astrocytes in the brain that talk to each other.This can be via gap junctions but also via chemical signals hence they’re releasing chemical signals (neurotransmitters).
• They will also be able to communicate with surrounding neurons.
• Astrocytes are involved in structural support, hence keeping neurons in the right position.
• Astrocytes are also important in development. During development they provide a scaffold which will guide the developing axons to the right places.
• They form part of the blood brain barrier
• They are involved in repair. If theres damage, astrocytes can form scar tissue which is referred to as a glial scar.
• Astrocytes are also involved in synapse function. They’re involved in formation of synapses and maintenance of the synapses once they’re formed. They can also affect neurotransmitter release at the synapse, so they can modulate neurotransmission.

Question 25

How do astrocytes maintain the extracellular environment?

Answer 25

For neurons to function, their environment must be kept constant.

For example, it’s important when neurotransmitters are released that they don’t remain in the extracellular fluid and are removed from the extracellular fluid. Astrocytes are important in maintaining that.

Neurotransmitters can be taken back into the presynaptic terminal and keep those levels low, which astrocytes help with. Astrocytes have transporters on their membranes, which allow the neurotransmitters to be taken into the cell, where they can breakdown the neurotransmitter, store the precursors and then return the precursors back to the neuronal cell.

Astrocytes are also important in keeping the extracellular potassium low. If the level of potassium is increased, the neurons will depolarise, which will stop the neurons from working properly.

Question 26

What are microglia?

Answer 26

Microglia are the immune cells of the CNS. They play roles such as scavengers, tidying up debris and release cytokines in order to mediate and coordinate the immune responses.

They can either be classed as resting or activated. When resting or activated, they perform different roles and are structurally different.

Question 27

What are resting microglia important in?

Answer 27

Homeostatic function

Question 28

What are activated microglia important in?

Answer 28

Activated microglia are more motile (so they can go off to places where they’re required).

They are pro-inflammatory, hence they’ll cause inflammatory reactions and release pro-inflammatory cytokines.

This is important for example, when there is an infection the microglia will be instrumental in trying to control that, which is a positive role.

However if this pro-inflammatory response gets out of hand, and is not being well controlled, then this can itself cause damage to the neuronal tissue.

Question 29

What are oligodendrocytes involved in?

Answer 29

Oligodendrocytes are the cells that form the myelin sheath around the neuronal axons in the CNS - the white matter.

Question 30

What are ependymal cells?

Answer 30

Ependymal cells are epithelial cells which line the fluid filled cavities i.e. ventricles of the CNS

They are responsible for secreting the cerebrospinal fluid (CSF)

Ependymal cells are ciliated. The cilia are important in moving around the cerebrospinal fluid within those ventricles.

As they line the ventricles, they form part of the BBB.

Question 31

What is glutamate?

Answer 31

Glutamate is the major excitatory neurotransmitter in the CNS.

Glutamate is a universal cellular constituent, meaning it is in all cells and is also an amino acid.

Glutamate can be synthesised within cells such as neurons therefore it is not an essential amino acid, which is only required from the diet.

Question 32

How can glutamate be synthesised?

Answer 32

Glutamate can be synthesised in the pre-synaptic neuronal terminal, as a bi product of the Tricarboxylic acid cycle (TCA) or the Kerb Cycle.

Glucose feeds into the TCA cycle and glutamate can be produced from the intermediate ‘a-Oxoglytarate’ by the action of the enzyme GABA-T.

Glutamate can also be produced from Glutamine via the action of the enzyme Glutaminase.

Question 33

How is glutamate synthesised step by step?

Answer 33

1. Glutamate (Glu) is produced in the neuron.
2. Once produced, it’s being loaded into our synaptic vesicle using the vesicular glutamate transporter (VGluT).
3. It is then stored in the synaptic vesicles ready to be released, following the appropriate signal from the neuron.
4. When that signal comes in, we get movement of our synaptic vesicles which fuses with the plasma membrane and release their contents into the synapse, which takes place through calcium dependent exocytosis.
5. The contents of our synaptic vesicles diffuse into and across the synpase, so we get glutamate being released, which can then act on the receptors. But it can also be taken up from the synapse and be recycled.
6. We have specialised transporter molecules in the cell membrane on both the neuron and the astrocyte, which can take up glutamate. These transporters are known as EAAT (Excitatory amino acid transporter). These are sodium linked transporters, which take up glutamate back up into those cells.
7. When we take it up into the astrocytes, it converts glutamate into glutamine by the action of the enzyme Glutamine Synthase and they store glutamate as an inactive transmitter in the form of Glutamine (Gln).
8. Glutamine can then be delivered back to the neuron by releasing it through the Glutamine transporters (GlnT) and is taken back up into the neuron and then can be converted back into Glutamate by the action of glutaminase.

Question 34

What 2 categories can glutamate receptors be separated into?

Answer 34

1. Metabotropic Glutamate Receptors
2. Ionotropic Glutamate Receptors

Question 35

What are metabotropic glutamate receptors?

Answer 35

They are G protein coupled receptors which rely on the generation of second messengers to send signals.

Question 36

What are ionotropic glutamate receptors?

Answer 36

They are ligand gated ion channels. These can be further subdivided into 3 types:

1. NMDA receptors
2. AMPA receptors
3. Kainate receptors

These 3 subtypes respond differently to the synthetic analogues. For example, the NMDA receptors only respond to NMDA and not to AMPA or Kainate, hence distinguishing the type of ligand gated ion channels from other ion channels that respond to glutamate. This is because all of the ionotropic glutamate receptors are responsive to glutamate which is the endogenous ligand.

• The 3 subtypes all have different pharmacological, biophysical and function properties in neurons.
• However they do have similar structures - Tetramers
• They are all activated by L-glutamate