CJH332

Synapse
Neurobiology
Week 5 – Part 1

Myelin – Part 2

Left - SEM of a bundle of myelinated nerve fibres. Myelin sheaths (yellow) can be
seen surrounding the axons (blue)
Nerve bundle, SEM - Science Photo Library
1
© CJH332 Neurobiology of the Synapse 2021
Term Test 1
• Term test 1 is now complete
• If you need a make-up test please consult the syllabus – you must do
this ASAP
• Grades will be released once the short answer section has been
graded
• Answers will be posted once grades are releases

© CJH332 Neurobiology of the Synapse 2021 2

Where we left off…
• EPSPs and IPSPs are summated at
the AIS/axon hillock

• Temporal vs Spatial summation

• Unidirectional nature of Aps

• Cable theory – compartments,

resistance, length constant

• Improving propagation

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Myelin Increases Conduction Velocity
• Myelin considerably increases the speed that APs move down the axons.
• Myelin prevents current from being lost as sodium ions drift away from the neuron

• For example, a thin diameter myelinated axon transmits impulses at anything from
5 to 30 metres per second whereas an unmyelinated one transmits them at 0.5 to 2
metres per second.

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Improving propagation
Increase the length constant (λ) by:
• Increasing the diameter (which decreases Raxial)
• Decreasing the leakiness of the membrane (which increases Rmembrane)

R membrane

R axial

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Glial cells are involved in myelination

• CNS
• Oligodendrocyte
• Astrocytes
• PNS
• Schwann cells

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Myelination
• Myelin wraps tightly around the axon
• There are many tight layers of wrapping

t • l.5

t=2

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Saltatory
conductance

From Latin saltare:

to jump, leap or
dance

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Advantages of saltatory
conductance ?
• FAST - Voltage-gated Na+ channels
are localized to the nodes, so
maximal current flow happens
there, but voltage changes
everywhere along axon

• EFFICIENT - Only have to put

energy (ATP) into maintaining
concentration gradient at nodes

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 Myelin and Saltatory Conduction
• Large vertebrate nerve
fibers are wrapped in myelin
sheaths formed by central
oligodendroglial cells or
Schwann cells in the
periphery
• Myelin is interrupted at
regularly spaced intervals,
or nodes
• During action potential
propagation excitatory
jumps from one node to the
next: saltatory conduction
• Much faster than passive
electronic spread

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 The Nodes of Ranvier A node of ranvier in
rat sciatic nerve

• Myelinated axons have four sodium channels (green)

distinct domains: node (N), potassium channels (red)
paranode (PN),
juxtaparanode (JPN), and
internode (INT)
• Voltage-sensitive Na+
channels are highly
concentrated in the nodes of
ranvier
• Potassium channels are
localized to the paranodal
and juxtaparanodal regions
• Why here - ion flow is restricted
here?
• This is still an area of active
research.

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 Myelin and Saltatory Conduction
• Are all neurons myelinated?
No.

• PNS
• Schwann cells
• Typically neurons less than 2 µm in
diameter are not myelinated

• CNS
• Oligodendrocytes
• most neurons with n axon diameter
larger than 0.2 µm are myelinated
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Formation of Myelin
• Schwann cell envelops the axon
and wraps itself tightly around it
• The thickness of the myelin
sheath is tightly regulated and is
highly correlated with the
diameter of the axon it
surrounds

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 Steps in forming the node of Ranvier
• Before glial ensheathment, sodium channels
are distributed uniformly, and at low density.

• At the time of glial ensheathment but before

the formation of compact myelin, loose
clusters of sodium channels develop at sites
that will become nodes.

• With formation of compact myelin and mature

paranodal axon-glial cell junctions, well-
defined nodal clusters of sodium channels are
established, and sodium channels are
eliminated from the axon membrane beneath
the myelin sheath
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 Steps in forming the node of Ranvier
• In this experiment they co-cultured rat dorsal root ganglion
neurons and Schwann cells.
• A myelinated nerve fiber was reproduced – the Schwann
cells wrapped themselves around the axons
• Myelin segments are stained in red by an antibody to
myelin basic protein (MBP), a molecule specifically
expressed in myelin
• Nodes of Ranvier (arrows) are stained in green by an
antibody to nodal molecule beta-IV spectrin.

Where else have

we seen B4-spectrin?

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 What happens if an axon is injured?
• In the mammalian CNS,
regeneration of severed
connections is typically
incomplete or absent
altogether.
• In the PNS, neurons are able
to regrow axons after injury
• Schwann cells and
macrophages phagocytize
the damaged axon and
myelin remnants.
• The axon regenerates along
a column of Schwann cells
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Na+ channels reorganize after injury
• The organization of the Na+
channels change after damage
or injury
• Before injury, there is high
density of channels at the
nodes
• Injury → disorganization →
inefficient or impaired AP
Nav1.6 propagation
• In the PNS this can be repaired,
but in the CNS this can be
permanent
• If not repaired, this can
Nav1.2 eventually result in a loss of
function as in the case of
Multiple Sclerosis (Fig d)
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Astrocytes: ‘a double edged sword’?
• Astrocytes support myelin
development
• They directly provide oligodendrocytes
with nutrients to support myelin sheath
formation and maintenance, via gap
junctions
• Astrocytes can support remyelination
• Astrocytes support remyelination by
providing cholesterol transfer and
secreting regenerative factors
• But astrocytes can also cause neural
damage
• Involvement in inflammatory processes

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Oligodendrocyte Development
• In development, oligodendrocytes are generated from neural stem cells
• Oligodendrocyte precursor cells (OPCs) eventually differentiate into
mature oligodendrocytes, before finally myelinating neurons

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 Oligodendrocyte Development

Brain: pre-OPCs born in

ganglionic eminences in
waves

Spinal cord: pre-OPCs

born in neuroepithelium

1. Neurons and radial glia are born first

2. Pre-OPCs born at 3 times points in the CNS: E12.5, E15.5, P0
3. Oligodendrocytes differentiate very late You really need to know this slide…..
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Markers expressed during oligodendrocyte development

• Oligodendrocytes express
unique markers
• Some are expressed only at
specific stages of development
• Some examples:
• Olig1/2: Only expressed by
oligodendrocytes
• Plp: A lipid protein expressed in
compact forms of myelin
• MBP: myelin basic protein,
expressed by myelin in both the
PNS and CNS
• MOG: myelin oligodendrocyte
glycoprotein, and important
structural protein

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Myelination in humans
• Humans are born with fewer
myelinated axons than other
mammals
• Myelination continues into the late
teens/ early 20s, this is an important
period of brain development
• The significance of this period?
• Still being researched
• There changes to executive and social
cognitive functions during adolescence
that may be related to the growth of
myelination

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 Steps in forming the node of Ranvier
• Glial processes wrap around axons
to form the myelin sheath
• Astrocytic processes cuff the nodes
• Myelin express NF-155, which
contacts Caspr/Contactin expressed
on the axon
• If this interaction is disrupted, the
paranodal loops of myelin are
everted away from the axon due to a
loss of junctions (transverse bands)

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Node of Ranvier – glia and neuron

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Things to re-visit and think about

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Is all myelin the same?
• CNS versions of myelin
• enriched for lipophilin also called proteolipid protein-1 (PLP-1) that helps to
compact myelin

• myelin associated glycoprotein (MAG) is likely involved in the initial

ensheathment.

• Both peripheral and central forms of myelin contain myelin basic protein (MBP)

• PNS – different series of proteins

• Myelin P0 and P2 proteins and peripheral myelin protein 22 (PMP-22)

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Summary
• Myelination improves action potential propagation and increases
conduction velocity
• Oligodendrocytes in the CNS
• Schwann cells in the PNS
• Gaps in myelin along the axon form the Nodes of Ranvier
• Saltatory conduction
• Organization of channels
• In the PNS, axons and myelin can be regenerated after injury
• Oligodendrocytes develop from neuronal precursor cells and express
different markers across their development
• Myelin expresses a number of important proteins that are not found in
other cell types

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