Myelin gets on your nerves

How is speed and efficiency in neural circuits achieved

• Neuron’s need fast signal transmission for efficient function.

• Myelin dramatically increases conduction velocity through saltatory conduction.

What is The Cable Theory / Equivalent Circuit Model

• Neuron is modeled as electrical compartments.

• Conduction depends on:

  • Resistance (how easily current flows)

  • Capacitance (ability to store charge)

What is the length constant

• Describes how far an electrical signal can travel before decaying.

• Larger axon diameter and myelination increase the length constant and speed.

Saltatory conduction

• Action potentials “jump” between Nodes of Ranvier.

• Nodes are rich in Na+ and K+ channels.

• Benefits:

  • Faster conduction

  • Lower energy cost (less ATP used for Na+/K+ pumps)

  • Compact wiring in the nervous system

What are the glial cells involved in

• CNS: Myelin is produced by oligodendrocytes.

• PNS: Myelin is produced by Schwann cells.

Schwann Cells vs. Oligodendrocytes

Feature	Schwann Cells (PNS)	Oligodendrocytes (CNS)
Developmental origin	Neural crest	Neurepithelium
Axon support	One axon per cell	Multiple axons per cell
Key proteins	P0 (myelin protein)	PLP (proteolipid protein)
Support cells	Direct axonal contact	Astrocytic interactions

Neural Crest Development

• Schwann cells originate from the neural crest.

• They sort axons by size and determine which ones get myelinated.

• Large axons → myelinated by Schwann cells

• Small axons → grouped into Remak bundles (non-myelinating)

Nodes of Ranvier

• Specialised domains between myelin segments.

• Critical for signal regeneration during conduction.

Summary of Feinberg et al., 2010 Findings:

• Showed that loss of gliomedin or CAMs like NF186 disrupts nodal assembly.

• Confirmed that nodal formation is not passive—it’s an active, cooperative process between axons and glia.

• Demonstrated how mutations or autoantibodies targeting these molecules (e.g., in autoimmune nodopathies) can lead to demyelinating neuropathies.

Classification of nerve fibres

Fiber Type	Function	Diameter (µm)	Conduction Velocity (m/s)
Aα	Motor to skeletal muscle (alpha motor neurons); proprioception from muscle spindles	13–20	80–120
Aβ	Touch, pressure (mechanoreceptors)	6–12	35–90
Aγ	Motor to muscle spindles (intrafusal fibers)	5–8	12–40
Aδ	Pain (sharp), temperature	1–6	5–35
B	Preganglionic autonomic fibers	<3	3–15
C	Pain (dull), temperature, itch; postganglionic autonomic	0.4–1.2	0.5–2.0

Diseases Involving Myelin Dysfunction (6)

• Multiple Sclerosis (MS) – autoimmune demyelination in CNS.

• Guillain-Barré Syndrome – acute inflammatory demyelination in PNS.

• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Charcot-Marie-Tooth Disease (CMT) – inherited neuropathy.

• Diabetic Neuropathy

• Chemotherapy-Induced Neuropathy

Charcot-Marie-Tooth Disease (CMT)

• Most common inherited neuropathy.

• CMT1A is the most frequent form.

• Caused by duplication of the PMP22 gene.

• Affects myelin thickness, conduction speed, and can result in “onion bulb” formations from repeated demyelination/remyelination cycles.

What are the different types of CMT

Type	Inheritance	Pathology	Gene Example	NCV	Notes
CMT1	Autosomal Dominant	Demyelinating	PMP22	<38 m/s	Most common type (CMT1A)
CMT2	Autosomal Dominant	Axonal	MFN2	>38 m/s	Milder, slower progression
CMT3	Variable	Severe demyelinating	MPZ, PMP22	Very slow	Infantile onset, also called DSS
CMT4	Autosomal Recessive	Demyelinating (severe)	GDAP1, SH3TC2	<25–30 m/s	Rare, often severe early onset
CMTX	X-linked	Demyelinating + Axonal	GJB1 (Cx32)	Mixed	Males more affected than females

What are 3 Clinical Implications of Demyelination

• Conduction Block: Myelin loss leads to slower or failed signal transmission.

• Axonal Damage: Without trophic support from myelin, axons degenerate.

• Remyelination Challenges:

  • New myelin is thinner

  • Shorter internodes

  • Results in slower conduction velocity

Demyelination

Demyelination and loss of ensheathing Schwann cells results in trophic deficit for neurons and axonal degeneration.

Remyelination

Remyelinated axons have shorter internodes and thinner myelin, resulting in lower conduction velocities.

Myelin and Circuit Tuning

• Myelin is not static — it’s involved in circuit refinement and activity-dependent plasticity.

• Adjustments in myelin contribute to fine-tuning of neural signaling.

• Example: Studied in electric fish and other models (Waxman et al.).

Myelination and Health Industry Relevance

• Understanding myelination informs:

  • Therapeutics for demyelinating diseases

  • Neuroprotection strategies

  • Biomarkers for neuropathies

• Autoimmune nodopathies: Involve antibody attacks at the nodes of Ranvier, disrupting conduction.