Nervous tissue is composed of two types of cells, neurons and glial cells. Neurons are the primary type of cell that most anyone associates with the nervous system. They are responsible for the computation and communication that the nervous system provides. They are electrically active and release chemical signals to target cells. Glial cells, or glia, are known to play a supporting role for nervous tissue. Ongoing research pursues an expanded role that glial cells might play in signaling, but neurons are still considered the basis of this function. Neurons are important, but without glial support they would not be able to perform their function.
Neurons are the cells considered to be the basis of nervous tissue. They are responsible for the electrical signals that communicate information about sensations, and that produce movements in response to those stimuli, along with inducing thought processes within the brain. An important part of the function of neurons is in their structure or shape. The three-dimensional shape of these cells makes the immense numbers of connections within the nervous system possible.
Parts of a Neuron
As you learned in the first section, the main part of a neuron is the cell body, which is also known as the soma (soma = “body”). The cell body contains the nucleus and most of the major organelles. But what makes neurons special is that they have many extensions of their cell membranes, which are generally referred to as processes. Neurons are usually described as having one, and only one, axon—a fiber that appears as a long cord emerging from the cell body and projects to target cells. That single axon can branch repeatedly to communicate with many target cells. It is the axon that propagates the nerve impulse, which is communicated to one or more cells. The other processes of the neuron are dendrites, which receive information from other neurons at specialized areas of contact called synapses. The dendrites are projections that branch many times, forming small, tree-shaped structures protruding from the cell body that provide locations for other neurons to communicate with the cell body. Information flows through a neuron from the dendrites, across the cell body, and down the axon. This gives the neuron a polarity—meaning that information flows in this one direction. Figure 1 shows the relationship of these parts to one another.
Where the axon emerges from the cell body, there is a special region referred to as the axon hillock. This is a tapering of the cell body toward the axon fiber. Within the axon hillock, the cytoplasm changes to a solution of limited components called axoplasm. Because the axon hillock represents the beginning of the axon, it is also referred to as the initial segment.
Many axons are wrapped by an insulating substance called myelin, which is actually made from glial cells. Myelin is a fatty substance that makes the axon appear white. It acts as insulation, much like the plastic or rubber that is used to insulate electrical wires. A key difference between myelin and the insulation on a wire is that there are gaps in the myelin covering of an axon. Each gap is called a node of Ranvier and is important to the way that electrical signals travel down the axon. The length of the axon between each gap, which is wrapped in myelin, is referred to as an axon segment. At the end of the axon is the axon terminal, where there are usually several branches extending toward the target cell, each of which ends in an enlargement called a synaptic end bulb. These bulbs are what make the connection with the target cell at the synapse.
Types of Neurons
There are many neurons in the nervous system—a number in the trillions. And there are many different types of neurons. They can be classified by many different criteria. The first way to classify them is by the number of processes attached to the cell body. Using the standard model of neurons, one of these processes is the axon, and the rest are dendrites. Because information flows through the neuron from dendrites or cell bodies toward the axon, these names are based on the neuron’s polarity (Figure 2).
Unipolar neurons have only one process emerging from the cell body which causes them to appear T-shaped. True unipolar cells are only found in invertebrate animals, so the unipolar cells in humans are more appropriately called “pseudo-unipolar” cells. Human unipolar cells have an axon that emerges from the cell body, but it splits so that the axon can extend along a very long distance. At one end of the axon are dendrites, and at the other end, the axon forms synaptic connections with a target. Unipolar cells are exclusively sensory neurons and have two unique characteristics. First, their dendrites are receiving sensory information, sometimes directly from the stimulus itself. Secondly, the cell bodies of unipolar neurons are always found in ganglia. Sensory reception is a peripheral function (those dendrites are in the periphery, perhaps in the skin) so the cell body is in the periphery, though closer to the CNS in a ganglion. The axon projects from the dendrite endings, past the cell body in a ganglion, and into the central nervous system.
Bipolar cells have two processes, which extend from each end of the cell body, opposite to each other. One is the axon and one the dendrite, forming a straight line. Bipolar cells are not very common. They are found mainly in the olfactory epithelium (where smell stimuli are sensed), and as part of the retina.
Multipolar neurons are all of the neurons that are not unipolar or bipolar. They have one axon and two or more dendrites (usually many more). With the exception of the unipolar sensory ganglion cells, and the two specific bipolar cells mentioned above, all other neurons are multipolar. Some cutting edge research suggests that certain neurons in the CNS do not conform to the standard model of “one, and only one” axon. Some sources describe a fourth type of neuron, called an anaxonic neuron. The name suggests that it has no axon (an- = “without”), but this is not accurate. Anaxonic neurons are very small, and if you look through a microscope at the standard resolution used in histology (approximately 400X to 1000X total magnification), you will not be able to distinguish any process specifically as an axon or a dendrite. Any of those processes can function as an axon depending on the conditions at any given time. Nevertheless, even if they cannot be easily seen, and one specific process is definitively the axon, these neurons have multiple processes and are therefore multipolar.
Neurons can also be classified on the basis of where they are found, who found them, what they do, or even what chemicals they use to communicate with each other. Some neurons are named on the basis of those sorts of classifications (Figure 3). For example, a multipolar neuron that has a very important role to play in a part of the brain called the cerebellum is known as a Purkinje (commonly pronounced per-KIN-gee) cell. It is named after the anatomist who discovered it (Jan Evangilista Purkinje, 1787–1869). These cells have a single, long, nerve tract entering the bottom of the cell body. Two large nerve tracts typically leave the top of the cell body but immediately branch many times to form a large web of nerve fibers. Therefore, the purkinje cell somewhat resembles a shrub or coral in shape. Pyramidal cells and olfactory cells are two other examples of neurons named for these classifications which will be discussed later.
Glial cells, or neuroglia or simply glia, are the other type of cell found in nervous tissue. They are considered to be supporting cells, and many functions are directed at helping neurons complete their function for communication. The name glia comes from the Greek word that means “glue,” and was coined by the German pathologist Rudolph Virchow, who wrote in 1856: “This connective substance, which is in the brain, the spinal cord, and the special sense nerves, is a kind of glue (neuroglia) in which the nervous elements are planted.” Today, research into nervous tissue has shown that there are many deeper roles that these cells play. And research may find much more about them in the future.
There are six types of glial cells. Four of them are found in the CNS and two are found in the PNS. Table 2 outlines some common characteristics and functions.
Glial Cell Types by Location and Basic Function
|CNS glia||PNS glia||Basic function|
|Oligodendrocyte||Schwann cell||Insulation, myelination|
||Immune surveillance and phagocytosis|
||Lining ventricles of the brain, creating CSF|
Glial Cells of the CNS
One cell providing support to neurons of the CNS is the astrocyte, so named because it appears to be star-shaped under the microscope (astro- = “star”). Astrocytes have many processes extending from their main cell body (not axons or dendrites like neurons, just cell extensions). Those processes extend to interact with neurons, blood vessels, or the connective tissue covering the CNS that is called the pia mater (Figure 4). Generally, they are supporting cells for the neurons in the central nervous system. Some ways in which they support neurons in the central nervous system are by maintaining the concentration of chemicals in the extracellular space, removing excess signaling molecules, reacting to tissue damage, and contributing to the blood-brain barrier (BBB). The blood-brain barrier is a physiological barrier that keeps many substances that circulate in the rest of the body from getting into the central nervous system, restricting what can cross from circulating blood into the CNS. Nutrient molecules, such as glucose or amino acids, can pass through the BBB, but other molecules cannot. This actually causes problems with drug delivery to the CNS. Pharmaceutical companies are challenged to design drugs that can cross the BBB as well as have an effect on the nervous system.
Like a few other parts of the body, the brain has a privileged blood supply. Very little can pass through by diffusion. Most substances that cross the wall of a blood vessel into the CNS must do so through an active transport process. Because of this, only specific types of molecules can enter the CNS. Glucose—the primary energy source—is allowed, as are amino acids. Water and some other small particles, like gases and ions, can enter. But most everything else cannot, including white blood cells, which are one of the body’s main lines of defense. While this barrier protects the CNS from exposure to toxic or pathogenic substances, it also keeps out the cells that could protect the brain and spinal cord from disease and damage. The BBB also makes it harder for pharmaceuticals to be developed that can affect the nervous system. Aside from finding efficacious substances, the means of delivery is also crucial.
Also found in CNS tissue is the oligodendrocyte, sometimes called just “oligo,” which is the glial cell type that insulates axons in the CNS. The name means “cell of a few branches” (oligo- = “few”; dendro- = “branches”; -cyte = “cell”). There are a few processes that extend from the cell body. Each one reaches out and surrounds an axon to insulate it in myelin. One oligodendrocyte will provide the myelin for multiple axon segments, either for the same axon or for separate axons. The function of myelin will be discussed below.
Microglia are, as the name implies, smaller than most of the other glial cells. They have rectangular bodies and many dendrite like projections stemming from their shorter sides. The projections connect at the dendrites and are so extensive that they give the microglial cell a fuzzy appearance. Ongoing research into these cells, although not entirely conclusive, suggests that they may originate as white blood cells, called macrophages, that become part of the CNS during early development. While their origin is not conclusively determined, their function is related to what macrophages do in the rest of the body. When macrophages encounter diseased or damaged cells in the rest of the body, they ingest and digest those cells or the pathogens that cause disease. Microglia are the cells in the CNS that can do this in normal, healthy tissue, and they are therefore also referred to as CNS-resident macrophages.
The ependymal cell is a glial cell that filters blood to make cerebrospinal fluid (CSF), the fluid that circulates through the CNS. Because of the privileged blood supply inherent in the BBB, the extracellular space in nervous tissue does not easily exchange components with the blood. Ependymal cells line each ventricle, one of four central cavities that are remnants of the hollow center of the neural tube formed during the embryonic development of the brain, as well as the central canal of the spinal cord. The choroid plexus is a specialized structure in the ventricles where ependymal cells come in contact with blood vessels and filter and absorb components of the blood to produce cerebrospinal fluid. Because of this, ependymal cells can be considered a component of the BBB, or a place where the BBB breaks down. These glial cells appear similar to epithelial cells, making a single layer of cells with little intracellular space and tight connections between adjacent cells. They also have cilia on their apical surface to help move the CSF through the ventricular space.
Glial Cells of the PNS
One of the two types of glial cells found in the PNS is the satellite cell. Satellite cells are found in sensory and autonomic ganglia, where they surround the cell bodies of neurons. This accounts for the name, based on their appearance under the microscope. They provide support, performing similar functions in the periphery as astrocytes do in the CNS—except, of course, for establishing the BBB.The second type of glial cell is the Schwann cell, which insulate axons with myelin in the periphery. Schwann cells are different than oligodendrocytes, in that a Schwann cell wraps around a portion of only one axon segment and no others. Oligodendrocytes have processes that reach out to multiple axon segments, whereas the entire Schwann cell surrounds just one axon segment. The nucleus and cytoplasm of the Schwann cell are on the edge of the myelin sheath. The relationship of these two types of glial cells to ganglia and nerves in the PNS is seen in Figure 5.
The insulation for axons in the nervous system is provided by glial cells, oligodendrocytes in the CNS, and Schwann cells in the PNS. Whereas the manner in which either cell is associated with the axon segment, or segments, that it insulates is different, the means of myelinating an axon segment is mostly the same in the two situations. Myelin is a lipid-rich sheath that surrounds the axon and by doing so creates a myelin sheath that facilitates the transmission of electrical signals along the axon. The lipids are essentially the phospholipids of the glial cell membrane. Myelin, however, is more than just the membrane of the glial cell. It also includes important proteins that are integral to that membrane. Some of the proteins help to hold the layers of the glial cell membrane closely together.The appearance of the myelin sheath can be thought of as similar to the pastry wrapped around a hot dog. The glial cell is wrapped around the axon several times with little to no cytoplasm between the glial cell layers. For oligodendrocytes, the rest of the cell is separate from the myelin sheath as a cell process extends back toward the cell body. A few other processes provide the same insulation for other axon segments in the area. For Schwann cells, the outermost layer of the cell membrane contains cytoplasm and the nucleus of the cell as a bulge on one side of the myelin sheath. During development, the glial cell is loosely or incompletely wrapped around the axon (Figure 6). The edges of this loose enclosure extend toward each other, and one end tucks under the other. The inner edge wraps around the axon, creating several layers, and the other edge closes around the outside so that the axon is completely enclosed.Myelin sheaths can extend for one or two millimeters, depending on the diameter of the axon. Axon diameters can be as small as 1 to 20 micrometers. Figure 1, Figure 4, and Figure 5 show the myelin sheath surrounding an axon segment, but are not to scale. If the myelin sheath were drawn to scale, the neuron would have to be immense—possibly covering an entire wall of the room in which you are sitting.
The nervous system
The nervous system can be organized in several different ways. For example, nerves can be classified based on their function. Afferent nerves carry information from sensory organs to the brain, while efferent nerves carry motor impulses from the brain to the muscles.Taking location into account, the nervous system can be divided into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of nervous tissue that is protected within bony structures – the brain within the cranium and the spinal cord within the vertebral column. The PNS encompasses all nervous tissue outside of bony structures, and includes all peripheral and cranial nerves, plexuses, and ganglia. Primarily, the PNS is made up of the axons of neurons whose cell bodies are located within the CNS (within the brain for cranial nerves and the spinal cord for peripheral nerves – yet another way to divide the nervous system based on location). The tissues of the nervous system can also be divided into grey matter and white matter. Grey matter is composed mainly of unmyelinated cell bodies and dendrites, and appears grey in color. White matter consists of myelinated axons. It is this myelin, a lipid-rich sheath covering axons, that causes white matter to be lighter in color than grey matter. In general, the brain is composed of an exterior layer of grey matter covering internal areas of white matter, with another internal layer of grey matter in the deepest part of the brain (called the basal nuclei). The spinal cord contains a butterfly-shaped area of grey matter surrounded by an outer layer of white matter. Confusingly, structures within white and grey matter are referred to by different terms, depending on whether they are located in the CNS or the PNS. A group of neuronal cell bodies is called a nucleus in the brain or spinal cord, and a ganglion in the PNS. Both will appear grey to the naked eye and under the microscope, due to their lack of myelin. Bundles of myelinated axons in the brain are called tracts, while bundles of axons in the PNS are called nerves. Different regions of the nervous system have distinct histological characteristics that make them easily recognizable, under the microscope.
The cerebral cortex
The sample on the slide below (Figure 7) was taken from the motor cortex, an area of the frontal lobe of the cerebral cortex that is involved in the conscious planning and execution of voluntary muscle movement. The predominant cells visible on the slide are called pyramidal cells (named for their triangular shape). Pyramidal cells in the cerebral cortex act as upper motor neurons, which then synapse with the lower motor neurons that are in direct contact with muscles to initiate contraction. The axons of pyramidal cells will descend through the interior white matter of the cerebrum into the three parts of the brainstem: the midbrain, the pons, and the medulla. Within the medulla, most axons will cross over to the opposite hemisphere of the brain from which they originated – – a process called decussation – – and then continue within the white matter of the spinal cord, before synapsing with interneurons and lower motor neurons, in the grey matter of the spinal cord. Remember, this entire pathway is traveled by cells whose axons may be three feet long!
Due the nature of histological sampling, it is impossible to see the entirety of a three-foot-long neuron on a single slide. In the above image, we can observe only the relatively large, triangular-shaped cell bodies of the pyramidal cells with clearly visible nuclei, parts of the dendrites, and the beginnings of axons.
The cerebellum is the part of the brain responsible for integrating input from the sensory organs to coordinate the precise, voluntary movements originally initiated in the cerebral cortex. The cerebellum consists of an outer cortex of grey matter covering an inner area of white matter, which itself surrounds a deeper layer of grey matter (called the cerebellar nuclei). The outer cerebellar cortex, shown in Figure 8, is tightly folded and has three distinct layers:
- the outer molecular layer, which has granules interspersed throughout
- the central layer of Purkinje cells
- the inner granular layer, composed mostly of densely packed granular cells.
Purkinje cells are typically arranged in a single row between the exterior molecular and interior granular layers. They are large, easily distinguishable, and have an extensive dendritic tree that is not visible in typical histology. To visualize this dendritic tree, an osmium stain can be used. Dendrites of Purkinje cells extend deep into the molecular layer, while the axons of Purkinje cells cross the granular layer and join other nerve fibers in the interior white matter of the cerebellum.
Remember, a nerve is a bundle of axons, running in parallel, in the PNS. As such, nerves do not contain neural cell bodies.
A longitudinal section of a nerve looks very different than a transverse section:
In a longitudinal section of a nerve (Figure 9), the axons stain darker and are visible as purple lines. The lighter-colored layers on both sides of the axon are myelin. These layers of myelin are many times thicker than the diameters of the axons. In the PNS, myelin is produced by Schwann cells, which wrap around the axon. The small gap in the myelin sheath that occurs between adjacent Schwann cells is called a node of Ranvier. Two nodes of Ranvier are circled in Figure 9 below.
In a transverse section of a nerve (Figure 10), single myelinated axons look like little circles organized in bundles called fascicles. The membrane wrapped around the fascicle is called an endoneurium and is made of the loose reticular connective tissue. The central axons are so thin that they appear as purple dots in the middle of the lighter-colored circles of myelin. This nerve was additionally stained with osmium and the membranes of myelin are visible as dark rings.
central nervous system (CNS)
node of Ranvier
peripheral nervous system (PNS)
- What is the distinction between the CNS and the PNS?
- Why is white matter lighter in color?
- In general, where in the brain can grey matter be found? How is this different in the spinal cord?
- What is the difference between a ganglion and a nucleus? between a tract and a nerve? Which are classified as grey matter? as white matter?
- Movement on one side of the body is often controlled by nerve impulses originating on the opposite side of the brain. What anatomical feature explains this phenomenon?
- Contrast the differences in the histological appearance of a pyramidal cell versus a Purkinje cell.
- Using only histological evidence, could you determine from where in the nervous system a sample of tissue was taken? How?