ArticlesHistologyTypes of tissuesNervous tissueNeuron histology

ArticlesHistologyTypes of tissuesNervous tissueNeuron histology

Neuron histology

Author: Lorenzo Crumbie, MBBS, BSc • Reviewer: Jerome Goffin
Last reviewed: July 17, 2023
Reading time: 17 minutes

Multipolar neuron (Neuron multipolare)

Prior to the late 19th century, neurons were viewed as collective functional units that formed a syncytium. Subsequent research showed that each neuron is capable of operating independently. This laid the foundation for what has been referred to as the neuron doctrine.

A neuron (nerve cell) is a specialized cell that conveys electrochemical impulses throughout the body. The cytology of a neuron facilitates the transmission of either:

'top-down' information from the brain to the periphery, via efferent neurons (e.g. to permit locomotion) (efferent neurons) or,
'bottom-up' information, in the opposite direction carrying sensory information the central nervous system, via afferent neurons (e.g. to alert the body of danger).

Key facts about neurons
Categories	Nuclei or laminae (CNS) or ganglia (PNS)
Communication	Via neurotransmitters across synapses
Neurotransmitters	Amino acids, catecholamines, cholines
Synapse	Presynaptic terminal, synaptic cleft, neurotransmitter, postsynaptic terminal
Structure	Cell body (soma), dendrites (covered with dendritic spines), axon, axon hillock. Nissl bodies
Types	Myelinated (nodes of Ranvier) vs nonmyelinated Multipolar, bipolar, pseudounipolar
Layers	Cerebrum - molecular, external granular, external pyramidal, internal granular, internal pyramidal, multiform layers Cerebellum - molecular, Purkinje, granular layers Peripheral nerves - epineurium, perineurium, endoneurium

This article will explain the histology of neurons, providing you with information about their structure, types, and clinical relevance. It will also cover briefly the histological layers of the central and peripheral nervous systems.

Contents

Overview
Cytology of the neuron
Types of neurons
Neurons of the central nervous system
Neurons of the peripheral nervous system
Clinical relevance
1. Wallerian degeneration
2. Axonal regeneration
Sources

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Overview

Neurons are one of the most diverse cellular populations in the human body. They have a wide variety of branching patterns that is characteristic of a particular subset of neurons. The size differences are also very eclectic. Some neurons are long, wide and myelinated (covered in myelin sheath), while others are short, narrow and unmyelinated.

Neurons have been grouped into two broad categories: those found in the central nervous system (brain and spinal cord) and those in the peripheral nervous system. In the central nervous system, they are found in clusters referred to as nuclei, or in layers also known as laminae. However, in the peripheral nervous system, they are found in ganglia.

Neurons are able to communicate with each other and with end organs (muscles, glands, etc.) with the aid of neurotransmitters. Neurotransmitters are small molecules that are synthesized in the cell body, stored in vesicles, transported within the axons along microtubules to the end of the nerve fibers where they are released when an appropriate stimulus is received. This article will focus on the general structure of neurons, in addition to differences between those found in the central nervous system and those found in the peripheral nervous system.

Cytology of the neuron

Cell body

The cell body is sometimes referred to as the perikaryon or soma. Like cell bodies of non-neuronal cells, it houses the nucleus and other organelles within its cytoplasmic membrane. In addition to carrying out general house-keeping functions (cellular repair, etc), the organelles of the cytoplasm are responsible for the synthesis of neurotransmitters (e.g. acetylcholine; ACh).

The soma has numerous cytoplasmic projections branching from its surface known as dendrites. These dendrites form specialized connections with other neurons in order to receive and process information. The dendrites are covered with even smaller projections called dendritic spines, which are the points of contact with axons from other neurons." These contact points are called synapses, and they can occur not only between two neurons, but between a neuron and a muscle fibre (neuromuscular junction).

Axon

The cell bodies of most neurons taper off and produce a long, solitary projection known as an axon. The axon is connected to the cell body by the axon hillock. The axon hillock is a portion of the soma that has clusters of microtubules, fine granular substances deep to the plasma membrane and dispersed collections of ribosomes. Unlike other areas in the soma, Nissl bodies (granular collections of rough endoplasmic reticulum) are seldom seen at the axon hillock.

Axons may be myelinated or unmyelinated, depending on their diameter. Myelin is a membranous sheath that insulates the axon. There are regions of the axon between bundles of myelin that remain bare, which are known as nodes of Ranvier. They promote rapid impulse transmission along the axon in a manner known as saltatory conduction. The rate of conduction increases with the diameter of the axon. Larger axons are typically more heavily myelinated than smaller axons, and consequently neurons with larger axons also transmit impulses faster than those with smaller axons:

Skeletal muscle (histological slide)
Type IA fibers have a diameter of 12 – 20 μm and transmit an impulse at about 70 – 120 m/s (meters per second). They are useful in carrying motor signals to skeletal muscles and relaying proprioception from the muscle spindles.
Type IB fibers are 10 – 15 μm in diameter and has a conduction rate of 60 – 80 m/s. They are involved with afferent relay from the tendons and skin.
Type II fibers conduct impulses around 30 – 80 m/s with a diameter of 5 – 15 μm. They carry touch sensation from Meissner’s and Pacinian corpuscles in the skin and proprioception from muscle spindles.
Aγ and Aδ fibers are both about 3 – 8 μm. However, the former has a conduction velocity of 10 – 30 m/s, while the latter conducts impulses at 15 – 40 m/s. They carry efferent information to muscle spindles and temperature and pain from free nerve endings, respectively.
White ramus communicans (cranial view)
Type B fibers are the smallest of the myelinated fibers. At 1 – 3 μm in diameter and a conduction velocity of 5 – 15 m/s, they are found in white rami and the fibers of CN III, CN VII, CN IX and CN X.
Unmyelinated fibers (type C/IV) are the smallest class of nerve fibers that carries pain, temperature and olfactory afferents. It has a diameter of 0.2 – 1.5 μm and conducts at a rate of 0.5 to 2.5 m/s.

The cells responsible for carrying out the myelination vary depending on whether the neurons are in the central nervous system (myelinated by oligodendrocytes) or in the peripheral nervous system (myelinated by Schwann cells). The end of the axon branches out into numerous projections called telodendria (s. telodendron).

Synapse

Neurotransmitters are released from the end of the telodendria onto neighbouring axons, somata, dendrites, or end organs to propagate the message being transmitted. These junctions are collectively known as synapses. They are specialized areas where chemical information is passed from a neuron to another neuron or end effector organ, resulting in the generation of an action potential.

The end of the preceding neuron constitutes the synaptic bulb, while the modified area of the subsequent neuron forms the synaptic cleft. The neurotransmitters are synthesized in the soma and stored in vesicles that are transported along the axon to the synaptic bulb. When a stimulus arrives at the synaptic bulb, the vesicle fuses with the cell membrane and is released into the cleft, where it binds to its corresponding receptor.

Neurotransmitters

Neurotransmitters can be classified as amino acids (glycine, gamma-aminobutyric acid and glutamate), catecholamines (norepinephrine or noradrenaline and dopamine), or cholines (acetylcholine). There are numerous receptors that respond to the varying neurotransmitters that are found in the synaptic clefts:

Catecholaminergic receptors such as α-, β-receptors and dopamine (D) receptors are activated by norepinephrine and dopamine, respectively.
Cholinergic receptors that are stimulated by acetylcholine (ACh) include muscarinic (M) and nicotinic (N) receptors.
There are also histaminergic (H) and serotonergic (5-HT) receptors that respond to the binding of histamine and serotonin, respectively.

The activity of the receptors can be modified by other neurotransmitters like glutamate (excitatory response) or glycine and GABA (inhibitory response).

Types of neurons

Multipolar

Neurons can also be classified based on the number of processes that emerge from the somata. The cells can either be multipolar, bipolar, unipolar or pseudounipolar. Multipolar cells are most predominant in the brain and spinal cord and are inclusive of motor neurons as well as interneurons. These cell types have a single axon extending from one end of the cell body and several dendrites branching as they protrude from the other side of the cell body. Because of the numerous branching, the cells appear fusiform or polygonal.

Bipolar

Bipolar cells are only associated with afferent impulses. They have a single axon projecting from one end of the oval cell body and a lone dendritic tree extending from the other end. These cells are found in the vestibulocochlear (hearing), olfactory and ocular (viz. retina) systems.

Unipolar

Unipolar cells are another subtype of neurons. They have a single axon projecting from the spherical cell body, while other regions of the cell membrane are devoid of dendritic branches. These cells are usually encountered in peripheral nerves and sensory ganglia.

Pseudounipolar

Pseudounipolar cells relate to an older nomenclature used to describe unipolar cells. The cell body, which is found in dorsal root ganglia, has one single process that serves both the role of the axon and the role of the dendrite. This process bifurcates close to the cell body and one branch (the central, or axonic) travels from the cell body to the spinal cord, while the other (the peripheral or dendritic) travels from the periphery to the cell body. These cells are associated with proprioception and joint position.

This quiz challenges you on the different nerve cell types. Give it a try!

Neurons of the central nervous system

The cerebrum (neocortex) and cerebellum are histologically divided into layers. The former has six layers, while the latter has three layers. Each layer within the respective region of the brain contains specific neurons.

The outermost layer (layer I) is the molecular layer, which contains the terminal dendritic and axonal branches. The axons arise from cells of the ipsilateral and contralateral hemispheres and the thalamus, while and most of the dendrites arise from the pyramidal cells. Retzius-Cajal cells can be observed between the axons and dendrites.
Small pyramidal cells and associated interneurons are seen in layer II (external granular layer).
Layer III (external pyramidal layer) contains pyramidal cells that become progressively larger in deeper regions of the layer. They act as commissural and association fibers in the cortex.
Layer IV, or the internal granular layer, primarily contains stellate cells and few pyramidal cells and interneurons.
The internal pyramidal layer, also known as layer V, contains the large pyramidal cells of Betz in the primary motor cortex of the frontal lobe. They send information to the striatum, spinal cord and brainstem, among other subcortical areas.
Finally, the multiform layer (layer VI) contains some pyramidal cells and interneurons. However, it is mostly populated by fusiform cells. Efferents from layer VI projects to the thalamus and claustrum.

The cell bodies of pyramidal cells, as their names suggest, have an apex and a base. There is a single dendrite arising from the apex of the cell (apical dendrite), which may branch subsequently. Furthermore, more dendrites extend from the base of the pyramid (basal dendrites). The cell size increases with each level. Other cell types are found in the cell layers, such as glial cells and granular cells.

The middle layer of the cerebellar cortex is known as the Purkinje cell layer. It contains pyriform (pear-shaped) cells with its dendritic branches projecting into the molecular (outer) layer. The inner cortical layer of the cerebellum (granular layer) has numerous small neurons, while the outer layer has few small neurons.

Neurons of the peripheral nervous system

Neurons of the peripheral nervous system are somewhat similar to those found in the central nervous system. They are continuations of the cranial and spinal nerves travelling through the spinal cord. Occasionally, mixed nerves, i.e. having both efferent and afferent properties, may be encountered in the peripheral nervous system. This permits bidirectional transmission of information between the brain and the end organs.

Peripheral nerve fibers are encircled by layers of connective tissue that divide clusters of nerve into fascicles. Groups of fascicles are surrounded by dense irregular connective tissue known as epineurium. The individual fascicle is then surrounded by a slightly thinner connective tissue layer known as perineurium. The endoneurium, which is a vascular, thin, loose connective tissue layer, surrounds groups of unmyelinated axons or single myelinated axons with their Schwann cells.

Clinical relevance

Wallerian degeneration

Wallerian degeneration refers to axonal breakdown distal to the point of injury. Typically, smaller neurons would be completely lost due to physical injury or diseases processes (infarction, autoimmune activity, etc) affecting the tissue. However, larger neurons can be partially damaged, resulting in a neuronopathy (damage to the soma) or an axonopathy (damage to the axon). If the cell body is destroyed, the axon becomes isolated and is no longer receiving necessary nutrients. Consequently, the axon will degenerate and the remnants are phagocytosed. However, if the cell body is preserved, then the axon distal to the lesion would degenerate as part of the Wallerian degeneration and regeneration process.

Wallerian degeneration in the peripheral nervous system includes:

Chromatolysis, or the transformation of Nissl substance to a finely granular dispersion within the first 24 – 48 hours.
Irregular swelling of the axon is also noticed in the first day of injury.
Two to three days later, there is a decline in electrical activity to the motor unit associated with the damaged nerve.
Axonal fragmentation occurs between 3 to 5 days post injury.
Disintegration of the myelin sheath also occurs within the first few days of injury.
10 to 20 days after the injury, the soma swells and the nucleus assumes an unconventional position. The degree of swelling is related to the proximity of the injury to the cell body.
Mononuclear leukocytes migrate to the affected area and congregate within the basal lamina of the column of Schwann cells (bands of von Büngner).
Denervation atrophy results in the associated effector units. In other words, the end organ associated with the damaged neuron loses its input.

Axonal regeneration

Subsequent regeneration of damaged cells is possible in the peripheral nervous system. This axonal regeneration involves:

Regeneration begins along the bands of von Büngner.
Schwann cells guide the growth of the budding axons towards the intended peripheral target. It is able to reach the previous target if growth beyond the point of injury is not obstructed.
It is unlikely that the regenerated neuron will exceed 80% of its previous diameter.
Denervation super-sensitivity refers to increased electrical stimulation of an end organ or muscle by a previously regenerated neuron. The over activity could be due to enhanced responsiveness or increased number of neurotransmitter receptors at the end organ, there is reduced reuptake of the secreted neurotransmitters, or the newly formed nerve fibers may be innervating additional regions of the end-organ.

Sources

All content published on Kenhub is reviewed by medical and anatomy experts. The information we provide is grounded on academic literature and peer-reviewed research. Kenhub does not provide medical advice. You can learn more about our content creation and review standards by reading our content quality guidelines.

References:

Eroschenko, Victor P, and Mariano S. H. di Fiore: Difiore's Atlas Of Histology With Functional Correlations. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008.
Gaudet, Andrew D, Phillip G Popovich, and Matt S Ramer: 'Wallerian Degeneration: Gaining Perspective On Inflammatory Events After Peripheral Nerve Injury'. Journal of Neuroinflammation8.1 (2011): 110.
Haines, Duane E, and M. D Ard: Fundamental Neuroscience For Basic And Clinical Applications. 4th ed. Philadelphia, PA: Elsevier: Saunders, 2013.
Kiernan, J. A, Murray Llewellyn Barr, and Nagalingam Rajakumar: Barr's The Human Nervous System. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins.
Palay, S. L.: 'The Axon Hillock and the Initial Segment'. The Journal of Cell Biology 38.1 (1968): 193-201.

Illustrators:

White ramus communicans (cranial view) - Rebecca Betts

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