Myelination is a crucial process in the nervous system, where a fatty substance called

myelin is formed around nerve fibers (axons) by specialized cells called oligodendrocytes in

the central nervous system (CNS) and Schwann cells in the peripheral nervous system

(PNS). Myelin acts as an insulating layer, speeding up nerve signal conduction and

protecting the axons. Here are some general rules of myelination:

1. Gradual Development: Myelination is not a one-time event but occurs gradually

during development. In humans, it begins before birth and continues throughout

childhood and adolescence.

2. Selective Myelination: Not all nerve fibers are myelinated. In the CNS, some
neurons remain unmyelinated, especially in areas responsible for fine control and

complex information processing. In the PNS, myelination is more widespread but

still selective.

3. Saltatory Conduction: Myelination increases the speed of nerve signal conduction.

This is achieved through a process known as saltatory conduction, where the action
potential "jumps" from one node of Ranvier to the next. This is much faster than

the continuous conduction seen in unmyelinated axons.

4. Node of Ranvier: In myelinated axons, the myelin sheath is interrupted at regular

intervals by small gaps called nodes of Ranvier. These gaps are essential for

saltatory conduction, as they allow the action potential to jump between them.
5. Energy Efficiency: Myelination is also energy-efficient. Because the action potential

only needs to be regenerated at the nodes of Ranvier, the neuron expends less
energy during signal conduction, which is vital in preserving the nervous system's

energy resources.
6. Schwann Cells and Oligodendrocytes: Schwann cells myelinate axons in the

peripheral nervous system, while oligodendrocytes do so in the central nervous

system. Schwann cells wrap around a single axon, whereas oligodendrocytes can

myelinate multiple axons.

7. Repair and Plasticity: The nervous system has some capacity to repair myelin
damage. In the PNS, Schwann cells can remyelinate axons after injury. In the CNS,
 this capacity is more limited, but there is ongoing research into stimulating

remyelination.

8. Disorders: Demyelinating diseases, such as multiple sclerosis, result in the loss of

myelin, disrupting nerve conduction and causing various neurological symptoms.

Understanding myelination is crucial for managing and developing treatments for

such conditions.

9. Timing and Sequence: Different types of neurons myelinate at different times

during development. Motor neurons, for example, myelinate relatively early, while

some sensory neurons may not be fully myelinated until later in life.
10. Importance for Learning and Memory: Myelination plays a role in learning and

memory processes. The speed and efficiency of nerve signal conduction affect how

we perceive and respond to the world around us.

In summary, myelination is a fundamental process in the nervous system, enabling rapid

and efficient nerve signal conduction while also protecting and supporting the axons. It's a
dynamic process that occurs over time, is selective in its application, and has significant

implications for nervous system function and health.

General Rules of Myelination References

1. Gradual Development

Myelination begins prenatally and continues into adolescence, with different regions of the brain myelinating at
different times.
Reference: Yakovlev, P.I., & Lecours, A.R. (1967). The myelogenetic cycles of regional maturation of the brain. In:

Regional development of the brain in early life. Blackwell Scientific.

2. Selective Myelination

Not all axons are myelinated. In the CNS, some neurons (especially those involved in complex integration) remain

unmyelinated.

3. Waxman, S.G. (1980). Determinants of conduction velocity in myelinated nerve fibers. Muscle & Nerve, 3(2), 141–
150. https://doi.org/10.1002/mus.880030207

4. Saltatory Conduction

Myelination enables saltatory conduction, where action potentials jump between nodes of Ranvier, greatly

increasing conduction speed.

5. Huxley, A.F., & Stämpfli, R. (1949). Evidence for saltatory conduction in peripheral myelinated nerve fibres. The

Journal of Physiology, 108(3), 315–339. https://doi.org/10.1113/jphysiol.1949.sp004335

 6. Nodes of Ranvier

These are periodic gaps in the myelin sheath where voltage-gated sodium channels are concentrated, critical for

saltatory conduction.

Reference: Salzer, J.L. (2003). Polarized domains of myelinated axons. Neuron, 40(2), 297–318.

https://doi.org/10.1016/S0896-6273(03)00628-7

7. Energy Efficiency
Myelination reduces the metabolic cost of action potentials by limiting the active membrane to the nodes of

Ranvier.

Reference: Harris, J.J., Jolivet, R., & Attwell, D. (2012). Synaptic energy use and supply. Neuron, 75(5), 762–777.

https://doi.org/10.1016/j.neuron.2012.08.019

8. Cellular Sources of Myelin

o CNS: Oligodendrocytes can myelinate multiple axons.

o PNS: Schwann cells myelinate only one segment of a single axon.

Reference: Simons, M., & Nave, K.A. (2016). Oligodendrocytes: Myelination and axonal support. Cold

Spring Harbor Perspectives in Biology, 8(1), a020479. https://doi.org/10.1101/cshperspect.a020479

9. Repair and Plasticity

Schwann cells promote regeneration in the PNS. In contrast, oligodendrocyte precursor cells (OPCs) in the CNS

have limited remyelinating ability.

Reference: Franklin, R.J.M., & Ffrench-Constant, C. (2008). Remyelination in the CNS: From biology to therapy.
Nature Reviews Neuroscience, 9(11), 839–855. https://doi.org/10.1038/nrn2480

10. Demyelinating Disorders

Conditions like Multiple Sclerosis involve autoimmune attacks on myelin in the CNS, impairing signal conduction.

Reference: Compston, A., & Coles, A. (2008). Multiple sclerosis. The Lancet, 372(9648), 1502–1517.

https://doi.org/10.1016/S0140-6736(08)61620-7

11. Timing and Sequence

Myelination follows a predictable sequence, with sensory and motor pathways maturing earlier than associative

areas.

Reference: Brody, B.A., Kinney, H.C., Kloman, A.S., & Gilles, F.H. (1987). Sequence of central nervous system

myelination in human infancy. Journal of Neuropathology and Experimental Neurology, 46(3), 283–301.
https://doi.org/10.1097/00005072-198705000-00003

12. Learning and Plasticity

Recent studies suggest that learning experiences can stimulate myelination and modify white matter architecture.
Reference: Fields, R.D. (2015). A new mechanism of nervous system plasticity: Activity-dependent myelination.

Nature Reviews Neuroscience, 16(12), 756–767. https://doi.org/10.1038/nrn4023

Comparative Table on Myelination

1. Brain Areas with Unmyelinated Nerve Fibers

Some regions of the brain contain a significant number of unmyelinated or lightly

myelinated fibers, particularly areas involved in local processing, complex integration,

or neuroendocrine functions. These include:

Some brain regions retain unmyelinated or sparsely myelinated fibers, often linked to local

processing and neuroplasticity:

Region Function / Reason Reference

Upper Layers of Cerebral Local circuitry, integration, Nieuwenhuys, R., et al. (2008). The Human Central Nervous

Cortex (e.g., Layer I) and plasticity. System. Springer.

High plasticity, frequent

Mori, K., et al. (2006). Current Opinion in Neurobiology, 16(6), 653–
Olfactory Bulb & Tract turnover of sensory
659. https://doi.org/10.1016/j.conb.2006.10.001
neurons.

Neuroendocrine

Hypothalamus integration—speed not Saper, C.B., et al. (2002). Comprehensive Physiology. Wiley.

critical.

Amygdala and Plasticity for learning and Amaral, D.G., & Lavenex, P. (2007). In: The Human Nervous System

Hippocampus emotion. (3rd ed.). Academic Press.

Slow autonomic and Parent, A. (1996). Carpenter’s Human Neuroanatomy (9th ed.).
Reticular Formation
arousal-related pathways. Williams & Wilkins.

Motor neurons myelinate earlier than sensory neurons because:

• Motor activity is essential for survival-related reflexes (e.g., sucking, breathing)

that must be functional at or near birth.

• Axonal activity accelerates myelination—motor neurons are more active earlier.
• Evolution favors early development of basic motor control.

Reference: Kinney, H.C., & Volpe, J.J. (2018). Myelination events and timing. In: Volpe’s Neurology of the Newborn (6th ed.). Elsevier.

Also supported by: Yakovlev, P.I., & Lecours, A.R. (1967). Regional development of the brain in early life. Blackwell Scientific.

2. Why Motor Neurons Myelinate Earlier than Sensory Neurons

Motor neurons myelinate earlier than sensory neurons due to developmental and
functional priorities:
 • Evolutionary and Functional Need: Early motor myelination is critical for survival-

related motor activities (e.g., reflexes, breathing, feeding).

• Peripheral Development Pattern: In general, efferent (motor) pathways develop

and myelinate earlier than afferent (sensory) ones.

• Activity-Dependent Myelination: Motor activity starts in utero and stimulates

earlier myelination.

3. Timeline & Comparative Table of Myelination

Myelination Timelines of Major Pathways

Myelination Fully
Pathway / Region Type Function Reference
Begins Myelinated By

~28 weeks ~2 years Voluntary motor Kinney & Volpe (2018); Brody
Corticospinal Tract Motor
gestation postnatal control et al. (1987)

~late 3rd ~6–12 months

Vestibulospinal Tract Motor Balance, posture Brody et al. (1987)
trimester postnatal

~birth to 3 ~2 years
Spinocerebellar Tracts Sensory Proprioception Yakovlev & Lecours (1967)
months postnatal

~2–3 years Fine touch,

Dorsal Column-Medial Sensory ~birth Kinney & Volpe (2018)
postnatal proprioception
Lemniscus

Brody et al. (1987); Kiernan,

~late fetal ~1 year Pain and
Spinothalamic Tract Sensory J.A. (2014). Barr’s The Human
period postnatal temperature
Nervous System

~32 weeks ~6–8 months Brody et al. (1987); Kinney &

Optic Radiation Sensory Visual processing
gestation postnatal Volpe (2018)

Giedd et al. (1999), Brain

~10 years Interhemispheric
Corpus Callosum Associative ~birth Development, Nature
postnatal communication
Neuroscience

Arcuate Fasciculus & Paus et al. (2001), Nature

~1 year ~20s (into
Other Association Associative Language, cognition Reviews Neuroscience, 2(10),
postnatal adulthood)
Fibers 700–709

References
 1. Kinney, H.C., & Volpe, J.J. (2018). Volpe’s Neurology of the Newborn (6th ed.). Elsevier.

2. Brody, B.A., et al. (1987). Sequence of CNS myelination in human infancy. J Neuropathol Exp Neurol, 46(3), 283–

301. https://doi.org/10.1097/00005072-198705000-00003

3. Yakovlev, P.I., & Lecours, A.R. (1967). The Myelogenetic Cycles of Regional Maturation of the Brain. Blackwell

Scientific.

4. Giedd, J.N., et al. (1999). Brain development during childhood and adolescence: a longitudinal MRI study. Nature
Neuroscience, 2(10), 861–863. https://doi.org/10.1038/13158

5. Paus, T., et al. (2001). Maturation of white matter in the human brain: a review of MRI and histological studies.

Nature Reviews Neuroscience, 2(10), 700–709. https://doi.org/10.1038/35094500

6. Kiernan, J.A. (2014). Barr’s The Human Nervous System: An Anatomical Viewpoint. Wolters Kluwer.

7. Nieuwenhuys, R., et al. (2008). The Human Central Nervous System. Springer.

Why Unmyelinated Neurons Contribute More to Plasticity

Unmyelinated neurons play a greater role in neural plasticity—the brain’s ability to

reorganize and adapt—due to their structural and functional characteristics that allow

slower, more modifiable signal conduction, local synaptic interaction, and greater

sensitivity to environmental input.

Mechanisms: Why Unmyelinated Neurons Support Plasticity

Mechanism Explanation References

Slower conduction Slower transmission provides more

Debanne, D., et al. (2011). Nat Rev Neurosci, 12(7), 375–
allows greater synaptic time for synaptic inputs to interact
387. https://doi.org/10.1038/nrn3065
integration and modulate outputs.

Unmyelinated axons are more

Lack of insulation
susceptible to neuromodulators and Fields, R.D. (2015). Nat Rev Neurosci, 16(12), 756–767.
allows local signal
ionic fluctuations, enhancing https://doi.org/10.1038/nrn4023
modulation
adaptability.

Higher metabolic
Without myelin, neurons require
demand promotes Harris, J.J., et al. (2012). Neuron, 75(5), 762–777.
more energy, linking metabolic state
activity-dependent https://doi.org/10.1016/j.neuron.2012.08.019
to functional changes.
plasticity

Unmyelinated axons and their

Greater capacity for Holtmaat, A., & Svoboda, K. (2009). Nat Rev Neurosci,
synapses can more easily sprout or
structural remodeling 10(9), 647–658. https://doi.org/10.1038/nrn2699
retract, supporting dynamic rewiring.
 Mechanism Explanation References

Myelination restricts synaptic

Late or absent
formation; regions that remain Mount, C.W., & Monje, M. (2017). Science, 356(6340),
myelination enables
unmyelinated retain lifelong 1238–1243. https://doi.org/10.1126/science.aam7670
lifelong plasticity
adaptability.

Myelinated vs. Unmyelinated Neurons & Plasticity

Feature Myelinated Neurons Unmyelinated Neurons Impact on Plasticity

Slow (continuous Slower signals allow more

Conduction Speed Fast (via saltatory conduction)
conduction) integration and adaptation.

More diffuse, local More synapses = greater capacity

Synaptic Density Fewer local synapses on axons
synapses for rewiring.

Highly plastic; more Structural plasticity favored in

Axonal Remodeling Structurally stable
dynamic sprouting unmyelinated axons.

Myelin Restriction on Myelin-associated proteins Supports new connections

No such inhibition
Synaptogenesis inhibit new synapse formation throughout life.

Susceptibility to High (exposed to Enhanced responsiveness to

Low (protected by myelin)
Neuromodulation extracellular environment) neurotransmitters and modulators.

Can persist into Lifelong capacity in unmyelinated

Plasticity Timeline Peaks early in development
adulthood neurons.

High metabolic activity linked to

Metabolic Efficiency Energy-efficient Energy-intensive
plastic processes.

References

1. Fields, R.D. (2015). A new mechanism of nervous system plasticity: Activity-dependent myelination. Nature Reviews

Neuroscience, 16(12), 756–767. https://doi.org/10.1038/nrn4023

2. Debanne, D., et al. (2011). Axonal computation. Nature Reviews Neuroscience, 12(7), 375–387.

https://doi.org/10.1038/nrn3065

3. Mount, C.W., & Monje, M. (2017). Wrapped to adapt: Experience-dependent myelination. Science, 356(6340),

1238–1243. https://doi.org/10.1126/science.aam7670

4. Holtmaat, A., & Svoboda, K. (2009). Experience-dependent structural synaptic plasticity in the mammalian brain.
Nature Reviews Neuroscience, 10(9), 647–658. https://doi.org/10.1038/nrn2699

5. Harris, J.J., et al. (2012). Synaptic energy use and supply. Neuron, 75(5), 762–777.

https://doi.org/10.1016/j.neuron.2012.08.019

6. Krasnow, A.M., et al. (2018). Regulation of myelin plasticity by neuronal activity. Annual Review of Neuroscience,

41, 75–97. https://doi.org/10.1146/annurev-neuro-080317-062158