Lecture 9 – 10.10.

2023
- Multiple Sclerosis
An autoimmune disorder that affects only CNS myelin (PNS Schwann cells are not
immunoreactive).
Affects oligodendroglia.
Presents as disruptions to movement, sensation, thought etc.

Plaques from damaged and dead myelin (oligodendroglia) are built up in the CNS.
Early detection helps effective treatment of the disease.

Cause – remains unknown.

1. Blood brain barrier and separation of the brain (therefore oligodendroglia and
majority of the body’s immune system) contributes to the disorder.
2. Known environmental factors –
Lack of vitamin D (people residing in northern and southern hemispheres of the
world have more prevalence due to lack of sunlight).
Smoking
Exposure to solvents and toxins
Diet
Genetics
- Back to how neurons communicate -
Again, NOT ELECTRICAL!
Propagation of signals (mainly through axons) is possible with
1. The principles of electrical potential difference.
2. Control of the movement of ions across membranes.
The “talking” and “listening” bits to neuron communication happens at the synapse and
it is chemical.
- Discovery of neurotransmitters –
By Otto Loewi.
With frog’s hearts.

- The first neurotransmitter –

Acetylcholine (ACh).
The most abundant neurotransmitter in the body.
Found at the neuromuscular junction.
Activates ion channels (ligand gated Na+ channels).
1. The ligand in this case will be ACh.
2. Na+ goes into the nerves at the muscle fibre and depolarizes the membrane potential.
Initiates muscle contraction.
 - The synapse –THIS IS IMPORTANT!!

- Parts of the synapse –

1. Presynaptic terminal/membrane – axon.
2. Synaptic vesicles – filled with neurotransmitters.
3. Synaptic cleft – junction point. Space is in millimeters (confirms the notion that
neurons are discrete units).
4. Postsynaptic terminal/membrane – contains receptors.

- Types of synapses –

Type 1
Excitatory (presynaptic terminal releases
excitatory neurotransmitters).
Initiates EPSP (excitatory post synaptic
potential).
Neurotransmitters gets the post synaptic neuron
to threshold potential -50 mV, and it opens
voltage gated Na+ channels.
Mainly Axo-dendritic.
Larger, denser
Type 2
Inhibitory (presynaptic terminal releases inhibitory
neurotransmitters).
Initiates IPSP. (inhibitory post synaptic potential).
Neurotransmitters gets the post synaptic neuron
further down from resting membrane potential -70
mV, and it opens voltage gated K+ channels.
Mainly Axo-somatic.
Smaller, dispersed.
- No need of slide 14!
- Release of neurotransmitters –
Ca2+ ions activate calmodulin.
Calmodulin cause mobilization of presynaptic vesicles.
Vesicles travel towards the presynaptic membrane.
Calcium is everything!!
Simplified (4 steps) –
1. Action potential reaches presynaptic terminal. It changes the membrane potential.
This induces influx of Ca2+ through voltage gated Ca2+ channels.
2. Ca2+ mobilizes presynaptic vesicles to fuse with the presynaptic membrane.
3. Vesicles undergo exocytosis, and neurotransmitter is released into the synaptic
cleft.
4. Vesicles recycle.

- Botulinum toxin –
A bacterial protein.
Disrupts the release of neurotransmitters from presynaptic vesicles.
1. Botulinum toxin is taken up into vesicles from the muscle fibre during the recycling
process of presynaptic vesicles.
2. When Calmodulin initiates the mobilization and fusion in the next cycle, botulinum
exits the presynaptic vesicle and cleaves proteins required in the fusion step of the
exocytosis process.
Muscle contraction is prohibited, and the muscle is now relaxed (flaccid).
 Details of the figure is not required for exams!!
- Post synaptic potentials –
- Depending on
1. the neurotransmitter released, and
2. the action of the post-synaptic receptors, the post-synaptic membrane potential may
change.
- The post synaptic potentials can be of 2 types -
1. EPSP – excitatory post synaptic potential.
2. IPSP – inhibitory post synaptic potential.
- What sort of ions moves from where to where when EPSP and IPSP are created? –

EPSP Na+ ions move inside the membrane.

IPSP K+ ions move outside the membrane.

- Post synaptic potentials – integration –

Synaptic signals do not dictate 100% of the post synaptic neuron’s actions.
Summation (calculation/decision) occurs along the post synaptic neuron’s membranes.
There are 2 types of summation –
1. Spatial
2. Temporal

- Temporal summation
The summation of postsynaptic potentials that reach the axon hillock at different times.
The closer in time the potentials occur, the greater the summation.

- Spatial summation
- The summation of postsynaptic potentials that reach the axon hillock from different
locations across the cell body.
- If this summation reaches threshold, an action potential is generated.
- Spatial and temporal summation – (from the textbook)

- Neural integration –
Ultimately summation occurs at the axon hillock.
Axon hillock contains lots of voltage gated Na+ channels.
What is being summed up? – all the EPSPs and IPSPs which come through different
dendrites of the neuron.
What is the result of the summation? –
if the final summed up voltage exceeds the threshold potential (-50 mV), it initiates
depolarization of the membrane.
If the final summed up voltage does not exceed the threshold potential, it does not initiate
the depolarization of the membrane. Further hyperpolarization occurs.