Axon

Axon
n., plural: axons
[æksɒn]
Definition: A long, slender projection of a nerve cell that conducts electrical impulses away from the cell body

What Is Axon?

An axon is a thin, long fiber of a nerve cell (or neuron). It transmits electrical impulses from the cell body (or soma) to the target cells, such as other glands, neurons, and muscles. It is a vital component of the nervous system, responsible for the transmission of signals, known as action potentials, across considerable distances. The axon ends in small branches called axon terminals, which form connections called synapses with other cells. These synapses allow the electrical signal to be transmitted as a chemical signal to other neurons or target cells.

Axons are typically covered by a myelin sheath, which helps to insulate and enhance the speed of signal transmission. They vary in length and can extend from a few micrometers to several feet in certain cases.

Let us learn more about axon definition, anatomy,  physiology, clinical significance, and history below.

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Anatomy

The axon is a specialized part of a neuron responsible for transmitting electrical signals. It has a distinct structure and is composed of several key components:

• Axonal region

The axonal region refers to the main body of the axon, which extends from the axon hillock to the axon terminals. It is a long, slender projection that varies in length depending on the type of neuron and its location in the nervous system. The axonal region is covered by the myelin sheath, which provides insulation and speeds up the transmission of electrical impulses.

• » Axon hillock

At the base of the axon, where it attaches to the cell body of a neuron, is a conical area known as the axon hillock. It plays a critical role in initiating and generating action potentials also called electrical impulses which travel along the axon. The axon hillock is rich in voltage-gated ion channels, which are responsible for the rapid changes in electrical potential necessary for signal propagation.

• » Axonal initial segment

The axonal initial segment or section is a specialized portion of the axon that immediately follows the axon hillock. It serves as the site where the action potential is first generated. The initial segment of an axon contains a high concentration of sodium channels. It is essential for the rapid depolarization that begins the action potential. This segment is crucial for the proper transmission of electrical signals along the axon.

• Axonal transport

Axonal transport is the cellular process by which materials, molecules, and organelles are transported bidirectionally along the axon. It involves two types of transport:

• 1. Anterograde, which moves substances from the cell body to the axon terminals
  2. Retrograde, which moves substances from the axon terminals back to the cell body. This essential process ensures the proper function and maintenance of neurons and their connections with other cells in the nervous system.

• Myelination

Axons within the nervous system can possess either myelin coating or lack it altogether. Myelination refers to the existence of the protective myelin sheath, which comprises a substantial ratio of lipids to proteins.

• Axons are myelinated by Schwann cells in the peripheral nervous system. These glial cells envelop the axons to form myelin sheaths.
• In contrast, the task of myelination is carried out by oligodendrocytes in the central nervous system. Remarkably, a single oligodendrocyte can myelinate as many as 50 axons.

• Nodes of Ranvier

Nodes of Ranvier are brief sections of unmyelinated axons. These specific locations serve to decrease the diameter of the axon. The presence of these nodes is crucial for the initiation of action potentials.

Saltatory conduction facilitates the transmission of electrical currents with minimal loss from one Ranvier node to the next. At each node, the electrical currents give rise to another action potential. This mechanism enables action potentials to “leap” between nodes, bypassing the need for myelinated segments. As a result, myelinated axons propagate at a faster pace compared to even the swiftest unmyelinated axons.

• Axon terminals

Axons can divide into multiple telodendria (Greek for “end of the tree“). An axon terminal ends each telodendron. The neurotransmitter is stored in synaptic vesicles in axon terminals. This allows neurons to form numerous synaptic connections. An autapse is when a neuron’s axon synapses onto its dendrite axon.

Following is the axon diagram:

Action Potentials

An action potential refers to the rapid and transient change in electrical potential that occurs along the membrane of the axon. It is a crucial process for transmitting electrical signals over long distances within the nervous system.

When an action potential is generated, the axon membrane depolarizes, meaning there is a rapid influx of positively charged ions, particularly sodium ions, into the axon. This influx of positive charges causes a localized alteration in the electrical potential, creating an electrical impulse.

Depolarization is initiated by the stimulation of the axon, either by sensory input or by signals from other neurons. This stimulation opens voltage-gated ion channels along the membrane of the axon, thus permitting sodium ions to enter the axon and causing a rapid increase in membrane potential. After the membrane potential reaches a certain threshold, it triggers a chain reaction where adjacent regions of the axon undergo depolarization. It leads to the propagation of the action potential along the length of the axon.

Following depolarization, the axon membrane undergoes repolarization, where the voltage-gated ion channels close, and potassium ions flow out of the axon. This restores the membrane potential to its resting state and prepares the axon cell body for subsequent action potentials.

The action potential travels down the axon in a wave-like fashion, allowing for rapid and efficient transmission of electrical signals from one end of the axon to the other. This enables communication between neurons and facilitates the relay of information throughout the nervous system (Raghavan et al., 2019).

Development And Growth

• Development

The process by which the axon in the body grows towards its goal is a key part of how the nervous system develops as a whole. Studies on growing hippocampal neurons show that neurons start by making several neurites that are the same, but only one of these neurites becomes the axon.

No one knows for sure if axon specification comes before or after axon elongation, but new evidence shows that axon elongation comes before axon specification.

When an undergrown axon is cut off, there is a probability that the orientation will get change. It could let other neurites grow into the axon. This change in polarity will occur only when the axon is cut off at least 10m shorter as compared to the other neurites. The longest neurite becomes the axon, while the remaining neurites, as well as the initial axon, transform into dendrites.

• » Extracellular signaling

In the extracellular matrix, some extracellular signals propagate axonal development. It includes adhesion molecules, proteins, extracellular matrix, and neurotrophic factors. The secreted protein Netrin, (UNC-6) aids in axon formation. When the mutation occurs in the UNC-5 netrin receptor some of the neurites are indiscriminately extended from neurons. It is followed by the anterior extension of a single axon. Neurotrophin-3 (NTF3), brain-derived neurotrophic factor (BDNFs), and neurotrophic factors nerve growth factor (NGF), bind to Trk receptors and are involved in axon development (Bakkum et al., 2019).

• » Intracellular signaling

At the terminal end of developing axons, PI3K activity increases during the development of axons. Its inhibition impedes the development of axons. Due to the activation of PI3K, the production of phosphatidylinositol trisphosphate increases. It leads to an increase in the size of the neurite and transforms it into an axon.

• » Cytoskeletal dynamics

An axon will develop from the neurite with the minimum concentration of actin filaments. When PGMS increases at the apex of a neurite, there is a significant reduction in the levels of f-actin. Exposure to actin-depolymerizing drugs and toxin B leads to the formation of multiple axons. The disruption of the actin network within a growth cone enhances the transformation of a neurite into an axon.

• Growth

Axonogenesis or axon growth is a fundamental process in the development and regeneration of the nervous system. During development, axons extend and navigate through complex environments to reach their target destinations. This process is guided by various molecular cues, including guidance molecules and cell adhesion proteins. These cues provide directional information, allowing axons to navigate along specific pathways and establish proper connections with their target cells.

The extension of growth cones, which are specialized structures at the terminal of growing axons, essentially drives axon growth. Highly dynamic growth cones respond to guidance cues by extending and retracting filopodia and lamellipodia, which are thin protrusions that explore the surrounding environment. These exploratory movements enable growth cones to sense and respond to attractive or repulsive cues, steering axons in the appropriate direction.

The growth of axons is also influenced by signaling molecules, such as neurotrophic factors, which promote axon survival, growth, and guidance. These factors provide essential support for axon growth by promoting the outgrowth of axons and preventing their degeneration.

In addition to development, axon growth is also critical for axon regeneration after injury. When an axon is damaged, the regrowth of the axon is facilitated by a series of cellular and molecular events. Axon regeneration is significantly facilitated by Schwann cells in the periphery and oligodendrocytes in the central nervous system. It is done by providing a conducive environment and producing growth-promoting factors.

• Length regulation

Axons exhibit a wide range of lengths, spanning from a few micrometers to meters in certain animal species. This demonstrates the existence of a cellular mechanism for modulating axon length. It allows neurons to detect the length of their axons and thus regulate their growth. Studies have revealed the crucial role of motor proteins in this length regulation process. Consequently, researchers have developed a comprehensive model to explain axonal growth, focusing on how motor proteins influence the length of the axon at the molecular level. The research shows that motor proteins transport signaling chemicals from the cell body to the axon development cone. With a frequency dependent on axon length, these signaling molecules oscillate.

Clinical Significance

There are different stages of how severe nerve injuries are, such as neurapraxia, axonotmesis, and neurotmesis. A weak form of diffuse axonal injury is a concussion. Central chromatolysis can happen when an axon is injured. Improperly functioning axons are a major cause of hereditary neurological illnesses that can affect both central and peripheral neurons.

Damaged axons deteriorate at the end farthest from the cell body. Macrophages shut off and break down damaged axons in Wallerian degeneration. This happens quickly after the injury. Neurodegenerative diseases can also cause axonal degeneration, especially when axonal action is slowed down. This is called Wallerian-like degeneration. Researchers think that this loss happens because the axonal protein NMNAT2 can’t reach the end of the axon.

Diffuse axonal injury, caused by severe traumatic brain traumas, damages axons. This can cause permanent coma. After multiple mild traumatic brain injuries in rats, a single mild traumatic axon brain injury can render it more vulnerable to subsequent damage.

Nerve guidance conduits are artificial tools used to guide axon growth and promote neuroregeneration. They are among the various treatments available for different types of nerve injuries.

History

Several well-known experts worked together to find the axon and figure out what it is.

• Otto Friedrich Karl Deiters, a German anatomist, is usually given credit for being the first person to tell the difference between an axon and a dendrite.
• The initial segment of the axon is first identified and characterized by Robert Remak and Rudolf Albert von Kolliker. The term “axon” was first used by Kolliker in 1896. Louis-Antoine Ranvier authored a paper on the branches and terminals of axons. These regions are now known as the nodes of Ranvier in his honor (Yaprak, 2008).
• Herbert Gasser and Joseph Erlanger classified peripheral nerve fibers by the size of the fiber, axonal conduction, myelination, and velocity. Their research established peripheral nerve function.
• Alan Hodgkin and Andrew Huxley conducted extensive research on the squid giant axon. It explains the ionic basis for the action potential which further leads to the development of the Hodgkin-Huxley model. Their groundbreaking contributions earned them the joint Nobel Prize in 1963. The Frankenhaeuser-Huxley equations describe the details of the axonal conductance of vertebrates.
• Ion channel details have been added to the molecular foundation of action potential propagation. These discoveries have improved our understanding of axon function and brain communication.

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Further Reading

• Human brain neuron

References

1. Bakkum, D. J., Obien, M. E. J., Radivojevic, M., Jäckel, D., Frey, U., Takahashi, H., & Hierlemann, A. (2019). The axon initial segment is the dominant contributor to the neuron’s extracellular electrical potential landscape. Advanced biosystems, 3(2), 1800308.
2. Kister, A., & Kister, I. (2023). Overview of myelin, major myelin lipids, and myelin-associated proteins. Frontiers in Chemistry, 10, 1041961.
3. Ozen, K. E., Kaya, D., Bahceci, S. A., & Malas, M. A. (2023). Microanatomic evaluation of the axon number and the parenchyma/stroma ratio of the sciatic and tibial nerves during human fetal anatomical development.
4. Raghavan, M., Fee, D., & Barkhaus, P. E. (2019). Generation and propagation of the action potential. Handbook of clinical neurology, 160, 3-22.
5. Yaprak, M. (2008). The axon reflex. Neuroanatomy, 7(1719.22).

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