Neurons, glia and divisions of the nervous system

Question 1

What is the general structure of a neurone?

Answer 1

Dendrites, cell body, axon.

The input is through the dendritic tree and the output is via an axon that branches several time before reaching target.

Perikaryon - cell body of a neuron

Cytoplasm of cell body is continuous with the dendrites and the axon. There is a raised area where axon leaves the cell body called the axon hillock, in this area the action potential is generated.

Question 2

What are the 4 main neurons we have in CNS and which is most common?

Answer 2

Multipolar neuron - multiple processes leaving cell body, some dendrites, one axon

Bipolar neurons - two axons leave cell body, one with dendrite end and one with terminals in CNS, not very common and tend to be in eye.

Pseudo-unpolar neuron - one branch leaves from cell body but it splits into axons. Example - cell bodies in dorsal route ganglia and axon extending into the periphery, axon terminates in spinal cord

Unipolar neurons - cell body moving onto a dendritic tree (in middle) and presynaptic terminals at end. Rare in vertebrates.

MOST COMMON - multi polar

Question 3

What does myelination do to an action potential?

Explain the structure of myelination?

Answer 3

Increases the conduction velocity.

Most axons are surrounded by myelin.
In the periphery, one Schwann cell will myelinate one axon. We do have multiple Schwann cells sitting along axon itself with a small gap (node or Ranvier) between them.
Rode of ranvier - unmyelinated region that allows for saltatory conduction of action potential.

The cytoplasm of Schwann cell extends thinly and wraps around the axon with myelin being produced through proteins on Schwann cell membrane. Little of of Schwann cell inside the axon (nucleus inside).
The layer of myelin are called lamellae.

Question 4

How do we classify nerve fibres?

Answer 4

• Amount of myelination.

The bigger the axon, usually the greater the amount of myelin and the greater the conduction velocity.
Can see that alpha motoneurons (innervate skeletal muscle) has a large diameter, they are myelinated extensively and conduct AP faster than other motoneurons.

Sensory - 1a and 1b afferents are the largest, they are move heavily myelinated and conduct the AP fastest of all the sensory neurons.

Not all axons are myelinated. Those concerned with pain are either lightly myelinated e.g. a delta nerves fibres or not myelinated e.g C fibres.

Question 5

Why is the nucleolus prominent in the neuronal cell body?

Answer 5

This is because the nucleolus is the site of ribosomal rRNA synthesis and neurons are translationally very active as they are continually producing neurotransmitters.

Question 6

Why is the chromatin in a neuronal diffuse?

Answer 6

Chromatin in nucleus is very diffused in the form of euchromatin. This is because the nucleus is post-mitotic so the cell is not undergoing division. No need for compaction of euchromatin into heterochromatin. It remains diffuse as lots of gene transcription and translation is occurring.

Question 7

How is the cytoskeleton organised in a neuron?

Answer 7

Same as any eukaryotic cell.

1. Microtubules. The largest. Within the neuronal call body to move organelle and within axon to transport molecules along the axon either to or from the cell body. Composed of alpha and beta tubules dimers.
2. Neurofilaments. Medium size. These help maintain neuronal structure and give the neuron a great deal of strength. Formed of intermediate filament composed of polypeptides.
3. Actin microfilaments. Smallest class. Help neurons move around PNS and CNS. Help maintain shape of neuron.

Question 8

What is anterograde and retrograde transport along a neuron?

Answer 8

Means by which cargo can be transported from cell body to nerve terminals =(anterograde axon transport)

Returned from nerve terminals to cell body =(retrograde transport)

Question 9

What molecules are responsible for anterograde and retrograde transport?

Answer 9

Anterograde - kinesins

Retrograde - dyneins

(Molecular motor - group of proteins that shuttle cargo from one part of cell to another (kinesins and dyneins).

Question 10

How is a neuron polarised?

Answer 10

They are polarised so that we have a negative end closest to cell body and a positive end closest to the nerve terminal.

Question 11

How do kinesins and dyneins move?

Answer 11

Kinesins move along the nerve terminal in anterograde direction. Work by having two heads on complex that detached and reattach after each other (one is always attached) in an ATP dependant manner. The molecular motor (kinesins in the direction) looks like it is walking along the nerve terminal towards the end of neurone. It will be carrying a molecule with it.

Dyneins work from the nerve terminals to the cell bodies, also ATP dependant. These move more by sliding along the microtubule.

Question 12

Give the properties of anterograde and retrograde transport

Answer 12

Anterograde transport can be either slow or fast. (Fast is conducted by kinesins).

Retrograde transport is fast and conducted by dyneins.

Both of these are still relatively slow (best being 400mm a day).

Why do we need these?
Kinesins moves neurotransmitters in vesicles and mitochondria. The NT are made in the soma, packaged into vesicle and then transported down.

Dyneins move along ageing organelles (mitochondria), recycling reasons (moving vesicles back to cell body) and signalling to cell body to know if there is any damage to nerve terminal to allow repair process to begin.

Question 13

What imaging can we use to see neurons?

What can we see?

Answer 13

Diffusion Tensor Imaging

Diffusion tensor imaging is a type of MRI working on principle of movement of water in axons can be visualised.

The computer here has focused on the seed point in the frontal lobe.
It has traced the axons to see the travel is posteriorly until the come to the anterior corpus callosum.
They travel through this area from right to left hemisphere and then they fan out.

Question 14

Explain what divergence an convergence is?

Give numbers of pre and post neurons

Answer 14

Convergence - many pre-synaptic neurons sending input to same post-syanptic neuron.

Divergence - single pre synaptic neurone diverging into multiple post-synaptic neuron.

Convergence:
The average CNS neurons receives 10,00 inputs (synapses). Some cells have more than this e.g purkinje cells of cerebellum where there are 300,000 different inputs.
Huge amount of information coming into neuron and decision here whether to fire an AP or not.

Divergence:
Tend to diverge to hundreds of different targets.

Question 15

What does convergence and divergence mean for the brain?

Answer 15

Many ways that neurons in the brain can make contact with neurons elsewhere in brain.

e.g neuron in frontal lobe has many ways that it can make contact with a neuron in the occipital lobe. Can go up through parietal lobe or by travelling through temporal lobe e.c.t
According to which route it took, different neurons would be activated or inhibited along the way. As a result, there will be different functional consequences.

The huge numbers of neurons through to exist in the brain e.g. 80-90 billion neurons. Each neuron on average receives 10,000 input meaning the possible routes are very large.

Question 16

How many glia are there compared to neurons?

Answer 16

Glis outnumber neurons by 10:1

Question 17

List the CNS glia and the PNS glia

Answer 17

CNS

• Ependymal cells
• Astrocytes
• Oligodendrocytes
• Microglia

PNS

• Satellite cells
• Schwann cells

Question 18

What are the main functions of astrocytes?

Answer 18

Their function can be divided into homeostatic and functional ones.

Homeostatic functions: those associated within synaptic environment so we find astrocytes around synapses.
These are called protoplastic astrocytes and they are responsible for regulating the ionic environment around synapse in particular potassium, potassium ions can be toxic so astrocytes take them up through projections and deposit them to areas where the potassium level is low.
They also maintain the acidity of the synapse and the water environment of synapse (osmotic environment).
They also take up a large number of NT including glutamate which is important as glutamate is toxic at high levels. Astrocytes covert glutamine into glutamine which is transferred back to pre-synaptic neuron for conversion back to glutamate to be reused.
Maintenance of blood-brain barrier
Uptake of neurotransmitters

Structural roles
Lying between cons along long axis to give stability and strength to nerves by bonding individual axons together
Actively inhibit regrowth of axons after damage - glial scar made of astrocytes to produce a variety of proteins (proteoglycans) that inhibit axon regeneration

Question 19

What are the two types of astrocytes?

Answer 19

Fibrous

• confined to grey matter
• wide range of homeostatic roles

Protoplasmic

• confined to white matter
• confer stability and support to axons

Protoplasmic astrocytes (found around synapses) have a greater number of shorter plasmic extensions.

Fibrous astrocytes (structural support) tend to have fewer but longer processes.

Question 20

What is the role of oligodendrocytes in the CNS?

Answer 20

Myelinating cells of CNS.

Differences with respect to Schwann cells:
Oligodendrocytes can myelinate multiple axons (40-50) where as schwann cells will only myelinate one axon.

An aspect of oligodendrocytes is that they can produce proteins that are inhibitory to axon growth after axon damage (same as astrocytes).

Question 21

How can we use oligodendrocytes to treat multiple sclerosis?

Answer 21

Oligodendrocytes are used in therapies where inflammatory response is aggregated by targeting T cells, often through use of steroids and also to try and stimulate oligodendrocyte pre cursor cells to produce more oligodendrocytes so there is a greater chance of the demyelinating axons being repaired.

Question 22

What is the role of microglia?

How are microglia activated?

Answer 22

CNS is not under normal check of the immune response due to blood-brain barrier. It needs it own mechanism to remove debris and for maintaining an immune defence mechanisms.
This is largely controlled by the microglia.

Normally, microglia have multiple processes extending from them. The shape of the cell means they are resting and not capable of being phagocytic to inject any unwanted material. 
However, they do express ATP receptors on the processes and one of the consequences of neuronal damage and inflammatory responses is ATP production. 
ATP binds to the P2Y receptor class on resting microglia and this causes the microglia to undergo conformational change where they become rounded by retracting processes. They are then capable of phagocytosis. This is in response from ATP signal from damaged cells or inflammatory responses.

Question 23

What is the role of ependymal cells?

What are the 3 types?

Answer 23

These from an epithelium lining of the ventricles of the brain and the spinal canal.

The ependymal cells are therefore in constant contact with CSF.
They secrete, monitor and aid the circulation of CSF.

The most common type are ependymocytes that have a ciliated villus border to aim the circulation of CSF. (May not be that useful as the CSF is under positive pressure as it is constantly produced, as well as this, they largely decrease in older age).

Tancytes are mainly found around third ventricle. They act as sensors for hormones in the CSF. In the third ventricle as this is where a lot of response to circulating homes occurs as the inferior part of third ventricle is made of the walls of the hypothalamus.

Choroid plexus cells are responsible for CSF production and secreting it into ventricular spaces. We find these in all ventricles of the brain but majority are in lateral ventricles.

Question 24

Explain the two neuroglia found in the PNS

Answer 24

Schwann cells - myelinating cells. Single cell wrapping around axon in a series of lamellae. Schwann cells promote axon regeneration (contrast to oligodendrocytes) by producing stimulatory factors such as neurotrophin (nerve growth factor) as well as nerve substrate molecules such as laminin and neuronal cell adhesion molecules. They rapidly remove myelin debris by phagocytosis.

Satellite cells - seem to be associated with sensory neurons in dorsal route ganglia associated with sympathetic neurons. We think they serve a smilier role to astrocytes by proving a homeostatic role for sympathetic and sensory neurones as well as structural support also.