We're all familiar with the nervous system in mammals (particularly humans) and how the various impulses and responses are communicated through the intricate neural network stemming from the brain and spinal cord. But, what would we find if we had to closely examine a synapse? The axon terminal is a critical part of the nervous system, and we'll investigate why below.
The axon terminal is an essential part of the neuron. The axon terminal is the "end-part" of the axon, which lies adjacent to a synapse, the gap between two consecutive neurons. Axon terminals play a fundamental role in facilitating intercellular communication through neurotransmitters.
The neuron is one of the most vital cells in the body. If nerve impulses are not effectively conducted through the body, the organism stands to suffer. The axon terminal plays a pivotal role in bridging the synapse. But how does it do this? Where exactly are axon terminals located? And what are some complications they experience?
An Axon Terminal’s Structure And Location
To better understand the axon terminal, we’ll begin by investigating where it occurs in the body, how it looks, and what it’s composed of.
The Definition Of A Axon Terminal
According to the Free Medical Dictionary, the axon terminal is the “ending of an axon which releases neurotransmitters into a synaptic space near another neuron, muscle, or gland cell.”
Another way to understand an axon terminal is its etymology (where the name derives from).
The name “axon” is from the Ancient Greek word (ἄξων) for “áxōn” or “axis.”
The “terminal” part of the name comes from the Latin word “terminalis,” which describes a boundary. “Terminalis” was derived from “terminus” (Latin), meaning “a limit, or an end.”
The Structure And Location Of Axon Terminals
Axon terminals occur at every synapse throughout the body (human and others). Axon terminals are button-like (or club-like) structures at the end of an axon. They are often enlarged compared to the rest of the axon. And are often branched.
Axon terminals have output receptors (synaptic terminals) on their ends which lie next to the synapse.
The axon (and therefore the axon terminal) forms part of the neuron (the nerve cell).
Neurons occur throughout the body and consist of:
- The cell body (soma). The soma houses the nucleus and other organelles.
- Dendrites. The root-like appendages branch from the soma. Many threadlike projections increase the surface area available for quicker communication.
- Conversely, the axon is a slender, unbranched, longer fiber extension, giving them their other name of “nerve fiber.” These axons vary in length, and humans can reach up to roughly 3 feet.
Larger axons in the peripheral nervous system are usually covered in a myelin sheath (myelinated). These myelin sheaths are made by Schwann cells.
- The axon hillock is the tapering region between the soma and the connected axon. Information from the dendrites is compiled here, and the axon hillock produces action potentials as required.
The Physiological Makeup Of Axon Terminals
Synaptic vesicles, containing neurotransmitters, “float around” in the axon terminals until they are activated. There are different types of vesicles located in the axon terminal.
A synaptic vesicle is a relatively small organelle (approximately 40nm). Due to the small size, synaptic vesicles can only accommodate a limited amount of proteins and phospholipids.
Although measurements are inconclusive, there are an estimated 10 000 molecules of phospholipids in each vesicle and roughly 200 proteins.
Some of the neurotransmitters within the synaptic vesicle include:
- Acetylcholine
- Adrenaline
- Dopamine
- Endorphins
- Enkephalins
- Glutamic acid
- Glycine
- Noradrenaline
- Serotonin
- Substance P
- Y aminobutyrate
The Purpose And Function Of An Axon Terminal
Axon terminals facilitate communication between the axon of one neuron and the dendrites of other neurons or effector cells (muscle and gland cells) across a synaptic gap.
The purpose of this synapse (connection gap) is to transfer “efferent” (outgoing) information (called action potentials and nerve impulses) “forward” through the axon of the presynaptic neuron into the postsynaptic neuron's (or other cells) dendrites.
There are two principal types of synapses.
- Chemical synapses. When nerve impulses/action potential moves from a neuron to a subsequent neuron or an effector cell, the information moves via chemicals in the axon terminal.
- Electrical synapses transfer messages at a faster rate. The gaps are much smaller, allowing the nerve impulse to bridge the gap between neurons faster than a chemical synapse. The synapse travels through gap junctions (pores) made of connexin proteins.
These signals carry a graded potential, which might not be strong enough to initiate the action potential needed for neurotransmitters.
Without the axon terminal and its associated parts, neurons could not communicate.
Scientists believe that the synaptic vesicles, located within the axon terminal, have the sole purpose of releasing neurotransmitters.
The exact “function” of many of the specific vesicle proteins is yet unknown (i.e., what specific proteins stimulate).
The table below examines some synaptic vesicle proteins and their functions.
| Protein | Function in the vesicle |
| Cysteine string protein | Function unknown. A Peripheral membrane protein. |
| Cytochrome b561 | This protein facilitates dopamine-β-hydroxylase and peptide amidase activity. It is an electron transport protein. |
| Neurotransmitter transporters | They facilitate the transfer of glutamate, acetylcholine, catecholamines, glycine/GABA, and ATP. |
| Rab3A, rab3C, rab5, rab7, and ra1 | They regulate the docking and fusing processes. |
| Rabphilin-3A | This protein assists in GTP by binding to rab3A and rab3C. It is a peripheral membrane protein. |
| SV2s | Unknown function. These are glycosylated proteins. |
Scientists divide these proteins into two categories.
- Transport proteins
- Trafficking proteins
How The Axon Terminal Works
Once the central nervous system (brain and spinal cord) sends an impulse, it sets in motion a “chain-reaction,” whereby the preceding neuron “tags” the postsynaptic neuron, perpetuating the nerve impulse.
The axon terminal contains neurotransmitters within “docked” vesicles. Thes docked vesicles are in a standby phase/state, waiting to be activated. The neuron requires an action potential to start the process.
An action potential is an eclectic charge that alters the neuron's membrane potential. Sodium moving into the cell while potassium moves out creates the action potential. When not in use, a neuron has a “resting potential.”
A voltage difference between the outside and inside of a neuron's membrane results in a charge. When neurotransmitters from the preceding neuron make contact, they initiate a change in the charge.
Once a graded or action potential (but mostly action) moves into the neuron, it triggers the neuron to permit access to free-floating calcium ions. The process behind the influx of calcium ions is the electrical depolarization of the membrane (at the synapse).
These calcium ions trigger the vesicles to fuse against the axon terminal’s membrane. These calcium ions also trigger the various proteins within the (synaptic) vesicle to form fusion pores along the axon terminal/vesicle membrane.
The neurotransmitters within the synaptic vesicles pass through the pores (they are released by exocytosis).
After passing through these pores, the neurotransmitters affect their targeted cells (by binding to the target cell’s receptors). Neurotransmitters are either inhibitory or excitatory in their function (i.e., they either decrease or increase a response).
As the neurotransmitters move between neurons, they bind to the postsynaptic neuron’s receptors (located on the membranes of the dendrites). Once this neuron receives the “information,” it creates an action potential in the axon hillock, which triggers the process.
The axon terminal allows the neuron to pass the information on to subsequent neurons through neurotransmitters and electrochemical signals.
The neurotransmitters only have a limited timeframe to act, and once their time expires, they are reabsorbed into the neuron they exited or broken down by enzymes.
The type of neurotransmitter released will determine the affected cell. For example, when the neurotransmitter acetylcholine moves into the synapse (once released by the neuron), it stimulates a muscle cell.
Axonal Transport Within The Neuron
Neurons are not equal in length. Those in the brain are conceivably shorter than those in the peripheries. In most neurons, the body (soma) is usually the same size. However, the axon length is what differs. The axons that stretch from the spinal cord to the feet are often up to 3.3 feet long.
The nuclease in the soma (cell body) synthesizes most of the important cell materials. Once synthesized, these materials must move throughout the neuron, including down the axon (until the axon terminal).
Any movement relating to the axon is referred to as axonal transport. Important to note is that the movement of cellular materials is a “two-way” street. When materials move toward the axon terminal, it's called anterograde transport.
When materials move away from the axon terminal (toward the soma), it's called retrograde transport.
Traffic flows both ways simultaneously in the neuron. Within the axon, microtubules provide "highways" for cellular materials to move. The "horsepower" for movement comes from motor proteins, which bind to the relevant material and move through the tubule.
Although vesicles, mitochondria, and other matter important to the neuron don’t travel through the tubule, the motor proteins act like a train, carrying their load along the microtubule train tracks.
Kinesin is the motor protein that moves material anterogradely, while cytoplasmic dynein moves materials retrogradely.
Some of the important materials which move from the soma to the axon terminal include:
- Proteins. Proteins are essential for a plethora of bodily functions, regulating, and other uses.
- Vesicles. Vesicles are essential for a neuron to communicate with postsynaptic neurons, glands, and muscle cells.
- Mitochondria. These energy supply cells are essential throughout the body for various processes. Without energy from mitochondria, the axon may not have enough “energy” to operate.
Why Correct Functioning Of The Axon Terminal Is Essential
The axon terminal is critical in inter-nerve cell communication by facilitating neurotransmitters moving from the presynaptic neuron to the target cell.
Without a properly functioning axon terminal, nerve cells could not pass messages through the body effectively, rendering the organism unable to function correctly.
Neurotransmitters are essential for various functions, like movement, metabolic activity, and hormone secretions.
In severe cases, a loss of functionality in the axon terminal could lead to paralysis (i.e., muscles no longer function as they should), injury (sensory nerves do not convey the message swiftly enough), and death (either through injury or loss of critical function like breathing).
Microtubules position themselves in all directions within the soma. Inside the axon, the microtubule’s positively charged end points toward the axon terminal, while the negatively charged end points towards the cell body.
Complications Of The Axon Terminal
Below we'll investigate how the axon terminal is negatively affected, including various diseases and injuries.
Toxins Bind To And Limit The Axon Terminal’s Function
Toxins affect neuromuscular interaction. In a healthy, functional system, the motor neurons (axon terminals) make a synapse with a skeletal muscle cell’s motor end plate.
As the action potential moves into the presynaptic neuron, it stimulates the neuron’s membrane to permit calcium ions to enter the cell. As these ions enter, the synaptic vesicles, which contain acetylcholine (a neurotransmitter), fuse to the axon terminal’s cell membrane.
Once fused, the neurotransmitters flood into the synapse and bind to receptors in the muscle cell membrane (specifically nicotinic acetylcholine receptors).
The purpose and result of this process are that the muscle contacts.
However, various proteins and other molecules are involved in this process, which is susceptible to toxins. These toxins bind to the proteins on either side of the synaptic rift.
Once bound, these toxins reduce or prevent the neuron's functioning, leading to muscle paralysis.
In medicine, doctors harness this binding trait of certain toxins to relax muscles for diagnostic and research purposes.
Congenital Myasthenic Syndromes
When the neuromuscular proteins mutate, it often leads to various congenital myasthenic syndromes. These syndromes result in impaired function within the axon terminal and the receptor cells of the postsynaptic cell.
The parts of the acetylcholine receptors are the most frequently affected areas.
These mutations potentially lead to muscle weakness and, in rare cases, congenital myasthenic syndromes.
The three commonly occurring autoimmune disorders affecting the neuromuscular junction are:
- Lambert-Eaton Myasthenic Syndrome.
- Myasthenia gravis.
- Neuromyotonia.
The Devastating Effects Of Trauma On The Axon Terminal
Trauma is another reason axon terminals (and neurons) no longer work effectively. For example, if an individual sustains a head injury, the axons are usually damaged, and the individual is often left in a vegetative state.
When an axon tears, it can also lead to loss of consciousness, axon degeneration, and eventual nerve death. When axons experience trauma (crushing or severing), it leads to Wallerian degeneration.
Sometimes damage and degeneration of the axon (and, by extension, the axon terminal) are due to diseases, including:
- Alzheimer’s disease (and other memory disorders)
- Amyotrophic lateral sclerosis (ALS)
- Huntington’s disease
- Parkinson’s disease
Conclusion
The axon terminal is a critical part of the already essential neuron. Axon terminals facilitate intercellular communication by allowing synaptic vesicles to bind to their membrane and release neurotransmitters into the synaptic rift after an action potential stimulates them. Without proper functioning of the axon terminal, the organism loses function. Several diseases and trauma affect the functioning of the neuron and axon terminal.
https://www.biologyonline.com/dictionary/axon-terminal
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/axon-terminal
https://organismalbio.biosci.gatech.edu/chemical-and-electrical-signals/neurons/
https://study.com/learn/lesson/what-is-an-axon-terminal-function-types.html
https://medical-dictionary.thefreedictionary.com/axon+terminal
https://kids.frontiersin.org/articles/10.3389/frym.2020.00012
