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Neurobiology
Cells of the nervous system
Anthony Heape
2010
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Cells of the nervous
system
Neuroglia : part 3
The non-excitable cells of the nervous system that
provide support to neuronal survival and function
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Myelination & Myelin Function
in the PNS
PNS
CNS

Oligodendrocytes
Form multiple myelin sheaths
around one or more axons
CNS

Schwann cells
Wrap around one portion of only one axon to
form a single myelin sheath
PNS
PNS
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Schwann cells are derived from the
neural crest
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“Schwann cells” proliferate and differentiate
while interacting with neurons
Jessen & Mirsky (2005) Nat. Rev. Neurosci. 6:671-682
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Early Schwann cell development
Schwann cells proliferate and
differentiate while invading
and delimiting distinct axonal
territories within the
developing nerve, forming
foetal nerve fibres: i.e.
bundles of non-segregated
axons enclosed within a
sheath of Schwann cells.
factors controlling early
Schwann cell development
P0
Jessen & Mirsky (2005)
Nat. Rev. Neurosci.
6:671-682
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“Schwann cell” phenotype evolves
during early development
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Kristjan R. Jessen and Rhona Mirsky (2005) Nat. Rev. Neurosci. 6:671-682
Radial sorting of axons by
Schwann cells
The Schwann cells surrounding the foetal nerve fibre
bundles secrete a basal lamina, proliferate and send
processes between the axons, eventually isolating each
axon from its neighbours in a Schwann cell envelope.
When radial sorting is complete, no axon is left in direct
contact with another axon.
However,...
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Radial sorting & axonal
envelopment
The type of Schwann cell sheath is determined by the axonal diameter
If axonal diameter
is less than 0.7 mm
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The basal lamina
When radial sorting is complete, the Schwann cell of each Schwann cell-axon unit
has secreted a basal lamina, isolating the unit from its neighbours.
The basal lamina is essential for the whole ensheathing process, from radial sorting
to myelination.
Basal lamina
Non-myelinating Schwann cells will form an
amyelin sheath
Promyelin Schwann cells will form a
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myelin sheath
The basal lamina
is essential
Abnormal basal lamina formation
results in diverse defects such as
absence of radial sorting,
hypomyelination and polyaxonal
myelination
Feltri & Wrabetz, (2005)
J. Peripheral Nervous
System 10:128–143
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Schwann cell sheaths in the
PNS
All mature Schwann cell sheaths are enclosed in a
basal lamina secreted by the Schwann cells.
CM
ax
Radial sorting
Fetal fibres
promyelin fibre
Sciatic nerve
(spinal nerve)
Basal
lamina
C-fibres
(ANS)
Vagus nerve
(cranial nerve X)
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From fetal bundle to myelin
factors controlling
Schwann cell development
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Promyelin fibre, mesaxon &
myelin formation
If axonal diameter is greater than 0.7 mm
“Under” or “over”, or...
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?
The chinese Yo-Yo
(David Colman)
early
MAG/GalCB
late
MAG/GalCB
Päiväläinen & Heape (2007). Mol. Cell. Neurosci. 35:436-446
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Proteins of PNS myelin
Non-compact
Garbay, Heape, et al. (2000) Progress in Neurobiology 61: 267-304
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Differential accumulation profiles of peripheral
nerve lipids during myelination
Myelination is accompanied
by a strong enrichment in
the galactosyl-cerebroside
(Gal-CB) content
peak
myelination
period
Garbay, Heape, et al. (2000) Progress in Neurobiology 61: 267-304
Heape et al. (1986)
Dev. Brain Res. 25:181-189.
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Differential expression of myelin
proteins in the PNS
MAG is expressed before MBP and the two proteins are spatially segregated
MBP is localized in compact myelin
MAG is localized in non-compact myelin
Päiväläinen & Heape (2007). Mol. Cell. Neurosci. 35:436-446
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Are MAG and gal-CBs
functional partners ?
Päiväläinen & Heape (2007). Mol. Cell. Neurosci. 35:436-446
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Proteins in the PNS nodal region
Salzer (2003) Neuron 40:297–318
NaV
MAG
Caspr
KV
Pedraza et al. (2001) Neuron 30:335–344
Päiväläinen & Heape (2007). Mol. Cell. Neurosci. 35:436-446
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Summary of
proteins in
the PNS
nodal region
MAG
Salzer et al. (2008) Glia 56:1532–1540
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Myelin compaction model
MAG is expressed before the major myelin proteins (P0 and MBP), establishing axon-Schwann cell
interactions and the primary mesaxonal spiral with 12-nm inter-membrane spacing.
Subsequent accumulation of large amounts of P0 and MBP (both have homophilic binding properties),
forces MAG out of large areas of the membrane, permitting P0- and MBP-mediated compaction.
Garbay, Heape, et al. (2000) Progress in Neurobiology 61: 267-304
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Myelin function in the CNS and PNS
• The myelin sheath is segmental, presenting discontinuities at ( ) regular intervals (forming the nodes of
Ranvier).
• Voltage-gated Na+ and K+ channels are clustered at the nodes.
• The lipid-rich, water-poor, nature of compact myelin gives the latter good electrical insulating properties.
• Action potentials are transmitted much faster along the axons (by saltatory conduction) due to the ion
channel clustering and the insulating properties of the myelin sheath.
Garbay, Heape, et al.
(2000) Prog. Neurobiol.
61: 267-304
1 mm (1000 nsec)
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Myelin and action potential transmission speed
The speed with which the action potentials are propagated along the axons depends on:
 The diameter of the axon (determines the number and surface density of voltage-gated ion channels)
 The presence, or absence of a myelin sheath around the axon (saltatory conduction is faster)
 The thickness of the myelin sheath (thicker is faster).
Nerve fibres (axons) of the PNS have been placed into 3
categories based on these criteria
A-fibres
belong to neurons of the somatic nervous system. They are generally medium- to
large-diameter axons with myelin sheaths of variable thickness.
A-fibres are further sub-divided into alpha (fastest: 100 m/sec), beta, delta and gamma
(slowest: 20 m/sec) fibres.
B-fibres
belong to neurons of the ANS. They are medium-diameter axons with thin myelin
sheaths, and an action potential transmission speed of 3 – 15 m/sec.
C-fibres
also known as ”Remak” fibres, belong to neurons of the ANS. They are small-diameter
axons with amyelin sheaths (i.e. no myelin), and an action potential transmission speed
of 0.7 – 2.3 m/sec.
Note:
different fibre types (A, B, or C) predominate in different peripheral nerves, but all three
may be present: e.g. B-fibres predominate in the vagus nerve, while A-fibres
predominate in the sciatic nerve.
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