Overview – Nerves
Plate 8-1. The Motor Neuron
Plate 8-2. The Myelinated Nerve Fiber
Plate 8-3. The Unmyelinated Nerve Fiber
Plate 8-4. The Myelin Sheath And The Synapse
Plate 8-5. Ganglion Cells Of The Autonomic Nervous System
The latest estimates place the number of nerve cells in the human nervous system at 100 billion. (The number of nerve cells in the nervous system is similar to the number of stars in our galaxy). In addition, each nerve cell can receive input from 1000 other nerve cells and send information to up to 1000 nerve cells. The tremendous complexity of the nervous system raises a question that puzzles neurobiologists of a philosophical bent: can the brain ever understand itself? We cannot now understand the nervous system; it is too complex, and we don’t know enough about it to explain basic phenomena, such as what a thought is, or how memory works. Nevertheless, great strides have been made in our understanding of the nervous system within the past century. We do, for instance, know a great deal about the structure and function of individual nerve cells.
The nerve cell, or Neuron, is the functional unit of the nervous system. Neurons are concerned with information transfer. There are three basic phases of information transfer in which neurons participate. First, they receive inputs from the environment, other neurons, or both. Second, they transmit information from one point in space to another. Third, they integrate and process information. Because neurons located in different places within the nervous system vary in structure, it is difficult to pinpoint a “typical” Neuron. Nevertheless, some structural features that are common to many neurons allow us to make some general statements about “the nerve cell.” Figure 8-1 is a simplified drawing of a Motor Neuron, a nerve cell that causes a muscle to contract. The Motor Neuronhas a large cell body, or Soma, in which the Nucleus resides. The Cytoplasmaround the Nucleus is often called the Perikaryon. The cell body gives rise to a very long and slender cylindric cytoplasmic extension, the Axon, that goes from the cell body to the muscle fibers innervated by the motor Neuron. The Axon may branch along its length, and each branch may have many functional endings that connect with many muscle fibers.
The point at which the Axon makes functional contact with the muscle Fiber is called the Motor End Plate, or the Myoneural Junction. Information travels along the Axon to the muscle Fiber in the form of an action potential, a kind of electrical excitation that does not decrease in strength with distance. The Action Potentialoriginates at the initial segment of the Axon as a result of electrical excitation the Motor Neuron receives from other nerves. These signals are received by the dendrites and cell body of the Motor Neuron. The dendritic tree is a vast system of branched cytoplasmic extensions that bring information from other neurons into the motor Neuron itself. The Motor Neuron, then, has dendrites that serve as the input stage, a cell body that is a receiving and integrating center, and an Axon that carries information away from the cell body to the “target” cells of the Motor Neuron — the muscle fibers with which it makes functional connections.
The nervous system is a giant, integrated communications network. For simplicity, neurobiologists have subdivided the nervous system into several categories, which, being artificial, overlap biologically. The nervous system is commonly subdivided into three major categories: the central nervous system, the peripheral nervous system, and the autonomic nervous system. The Central Nervous System is that part of the nervous system consisting of the brain and spinal cord. The peripheral nervous system is that part of the nervous system consisting of the nerves outsidethe brain and spinal cord. The Autonomic Nervous System, which is subdivided into the sympathetic and parasympathetic nervous systems, is that part of the nervous system that participates in the regulation of the activity of Smooth Muscle, cardiac muscle, and glands. The overlap between the central, peripheral, and autonomic nervous systems underlies the operation of an integrated nervous system. Consider, for example, a motor neuroon that innervates a runner’s Gastrocnemius (calf) muscle. The cell body of that Neuron is in the spinal cord and hence is the Central Nervous System. Its Axon, which leaves the spinal cord and travels to the Gastrocnemius in a large nerve trunk, is in the peripheral nervous system.
In addition to neurons, the nervous system contains supporting cells called neruoglia, also known as glia or glial cells. Just as there is a variety of nerve cells, so is there a variety of glial cells. One example of a glial cell is the Schwann Cell — the cell that generates the Myelin Sheath that covers many large axons in the peripheral nervous system. Another example of a glial cell is the Oligodendrocytewhich gnerates the Myelin Sheath of some axons within the Central Nervous System. In general, nerve cells cannot exist without glia, and they die very quickly without their support. A related distinguishing feature of nerve cells in the human nervous system is that nerve cells are a static cell population. Unlike epithelial cells, they do not turn over during the life of the individual. Once the cell body of a Neuron dies, it is lost for all time, and cannot be replaced by mitotic activity of other cells. (there is one known exception to this rule; olfactory receptor neurons, described in Chapter 20, do turn over during life, and lost cells can be replaced by mitotic activity of basal cells). Consequently, neuronal degeneration can have disastrous effects. In the crippling disease Poliomyelitis, for example, the polio virus takes residence in the cell bodies of motor neurons within the ventral horn of the spinal cord. If the viruses kill the cell body, the motor Neuron dies, its Axondegenerates, and the individual can no longer move the muscle fibers originally innervated by the destroyed neurons. The severity of the ensuing paralysis depends upon the number and location of the infected motor neurons.
Given the complexity of the nervous system, the objective of this chapter is to present the microanatomy of several prototypes of major classes of nerve cells in order to facilitate their recognition and understanding in histological material. The chapter starts with the motor Neuron described above and moves on to describe myelinated nerve fibers, unmyelinated nerve fibers, the Myelin Sheath, the Synapse by which nerve cells communicate with one another, and Ganglion cells of the Autonomic Nervous System. Careful study of the light and electron micrographs should greatly facilitate your recognition and understanding of nerves encountered in sectioned material.
The Motor Neuron
The Motor Neuron, such as the one depicted at right, is one of the largest kinds of nerve cell in the nervous system. Motor neurons are important to proper body function because they are responsible for exciting the skeletal muscles that power our voluntary movements. Each Motor Neuron houses its cell body within the spinal cord. From there, it sends a long Axon out into the periphery; the Axonterminates by making synaptic contact with one or more Skeletal Muscle fibers. Take, for example, one of the motor neurons that innervates the muscles that move one of your toes. Its cell body, which measures some 50 Â µm in diameter, is in your spinal cord; its Axon, some 3 m long, travels out of the spinal cord, down your leg, and into your foot to its point of contact with the specific muscle fibers it innervates. Consequently, the cell body is charged with the manufacture and maintenance of a vast amount of axoplasm. It is not surprising, then, that the cell body of the Motor Neuron contains much of the biosynthetic material essential for large-scale macromolecular synthesis.
Figures A and B at right are a matched pair of light and electron micrographs of serial sections taken through the ventral horn of the spinal cord, a region inhabited by many motor neurons. In this field, the same motor Neuron is seen by light and electron microscopy. The large cell body, or Soma, contains a round, centrally located, euchromatic Nucleus (N) with a conspicuous Nucleolus. In the light micrograph, the cell body contains a large quantity of highly basophilic material known as Nissl Substance (Ni). Also called Nissl Bodies, the basophilic material consists of the cytoplasmic machinery responsible for protein systhesis: the rough Endoplasmic Reticulum and a large number of free ribosomes. When viewed by electron microscopy (Figure B), the granular nature of the Nissl Substance is evident even at this relatively low magnification. The granular appearance of the Nissl Substance is created by the large population of ribosomes, which look like small dark dots in thin sections. Some large, electron-dense inclusions represent Lipofuscin Granules (L), often called “wear and tear granules,” which are darkly pigmented, membrane-limited bodies that are secondary lysosomes filled with indigestible material sequestered from the rest of the Cytoplasm. Since neurons are not replaced by mitotic activity, the number of lipofuscin granules within motor neurons tends to increase with age.
Although the geometry of the Motor Neuron is not evident in sectioned material (see Figure 8-1 for an illustration of a Motor Neuron), some of its cytoplasmic extensions are evident in the photomicrographs at right. A large Dendrite (D) reaches out from the right side of the cell body. At the left of the cell body, one of many smaller incoming dendrites (D) may be seen. Surrounding the Motor Neuronare a number of components of the spinal cord, such as capillaries (C) and myelinated nerve fibers (NF).
Plate 8-1, Figures A and B. Matched pair of light and electron micrographs of serial thick and thin sections taken through the anterior (ventral) horn of the spinal cord. C, capillary; D, Dendrite of Motor Neuron; L, Lipofuscin Granules; N, Nucleus; NF, cross section through myelinated nerve Fiber; Ni, Nissl Substance; S, Soma (cell body) of Motor Neuron. 2000 X
The Myelinated Nerve Fiber
As described in the previous plate, each Motor Neuron has an Axon that extends from the nerve cell body to the Axon‘s destination, a Skeletal Muscle Fiber. Plate 8-2 is an electron micrograph of a longitudinal section taken through a group of large myelinated axons of motor neurons that course through a peripheral nerve. Because each Axon is tubular, its profile, when cut in longitudinal section, resembles a soda straw split in half. In Plate 8-2, each Axon (A) contains a core of pale axoplasm. The axoplasm contains many slender Mitochondria (arrowhead) and is supported by cytoskeletal elements including microtubules and Neurofilaments. The microtubules and Neurofilaments, too small to be individually resolved at this magnification, appear as wispy strands. Each of these axons is covered by an electron – dense Myelin Sheath (M). The Myelin Sheath, composed of the compressed, spiral wrappings of the Plasma membrane of a Schwann Cell, acts as an electrical insulator. The nuclei (N) of several Schwann cells are evident near the top of the field of view. At the periphery of the Myelin Sheath, a thin layer of Schwann Cell Cytoplasm (*) is visible.
At many points along the length of the Myelin Sheath are discontinuities in the myelin called Schmidt-Lantermann clefts. Their function is unknown. Other discontinuities in the Myelin Sheath, called the nodes of Ranvier (not shown here), are better understood. They represent gaps between the myelin sheaths laid down by Schwann cells that lie next to one another along the length of the Axon. (If you were to firmly grasp a garden hose in both hands, the hose would represent the Axon, each hand would represent a Schwann Cell and the Myelin Sheath beneath it, and space between your hands spanned by the naked hose would represent a Node of Ranvier.) The nodes of Ranvier, which may be spaced at 1-mm intervals from one another along a large Axon, accelerate the rate at which the nerve impulse travels along the Axon. Nerve impulses can travel rapidly. Large axons, such as those of motor neurons, can reach 30 Â µm in diameter and have a conduction velocity of 100 m/sec. In contrast, small axons, such as those of olfactory receptor neurons, may be as small as 0.1 Â µm in diameter and have a somewhat sluggish conduction velocity of 0.5 m/sec.
The relatively “empty” appearance of the axoplasm (A) is due largely to the absence of cytoplasmic organelles associated with protein synthesis. The Axon has neither rough Endoplasmic Reticulum nor free ribosomes. Consequently, its protein must come from a distant source-the cell body. Protein synthesized in the Nissl substance within the nerve cell body travels down the Axon by an active, energy-dependent process known as Axoplasmic transport. Although rates of Axoplasmic transport vary in different axons, and even within the same Axon, a good average rate of transport observed in many axons is about I mm/day. The rate of regeneration of severed axons proceeds at the same rate – about 1 mm/day. Should the Axon of a Neuron be severed but its cell body and Schwann Cell sheath remain intact, a new Axon, derived from materials synthesized in the cell body, can grow down through the Schwann Cell sheath and reestablish its original pattern of connection.
Plate 8-2, Electron micrograph of a longitudinal section through axons of motor neurons within a peripheral nerve. A, Axon; CT, connective tissue of Endoneurium; M, Myelin Sheath; N, Nucleus of Schwann Cell; *, Cytoplasm of Schwann Cell; arrow, Schmidt-Lantermann cleft; arrowhead, mitochondrion in axoplasm. 1,400 X
The Unmyelinated Nerve Fiber
As described in the overview to this chapter, the term “nerve Fiber” commonly refers to a single Axon and its sheath. Plate 8-2 showed the myelinated nerve Fiber. Plate 8-3 shows the unmyelinated nerve Fiber. An unmyelinated nerve Fiber, as its name indicates, does not have a Myelin Sheath; its sheath, in the case of a peripheral nerve, consists of a Schwann Cell and its Basement Membrane.
The plate at right is an electron micrograph of a cross section taken through a small peripheral nerve found in the spermatic cord of the squirrel monkey. Much can be learned from close study of this micrograph, since it contains a variety of permutations and combinations of axons and their sheaths. At lower left in the field, for example, a cross-sectional image of a small myelinated Axon (M) is evident. Here, the Schwarm cell responsible for the formation of the Myelin Sheath has been cut at the level of its Nucleus (N’). Note that a single Schwann Cell typically ensheathes a single Axon in the peripheral nervous system. At the top of the field, an Axon undergoing myelination is visible (AM). Here again, a single Schwann Cell is associated with a single Axon. The remainder of the field, however, is filled with unmyelinated axons. In some cases, a single unmy- elinated Axon is encased within the Cytoplasm of a single Schwann Cell (A). In other cases, many unmyelinated axons are surrounded by the Cytoplasm of one Schwann cell. In the nerve bundle labeled A’, for example, 15 unmyelinated axons are invested by one Schwann Cell. A more striking example is evident at far left within the plate; a bundle of unmyelinated axons are arranged radially at the periphery of a small nerve bundle, in the center of which sits the large Nucleus (N) of a Schwann cell.
All of the nerve fibers within this small peripheral nerve are surrounded by a delicate support system of loose connective tissue fibrils (CT) that comprise the Endoneurium. The connective tissue of the Endoneurium is elaborated by a small number of fibroblasts, one of which (F) is present in the center of the field of view. The perimeter of the peripheral nerve is, in this case, defined by a sheath called the Perineurium (P), which consists of cells and connective tissue. Large peripheral nerves are surrounded by a thicker sheath called the Epineurium. Small peripheral nerves such as the one shown here, however, do not have an Epineurium and are protected by a perineurial sheath alone.
Plate 8-3, Electron micrograph of a cross section taken through a small peripheral nerve in the spermatic cord of the squirrel monkey. A, single unmyelinated Axon in Schwann Cell sheath; A’, group of unmyelinated axons ensheathed by a single Schwann cell; AM, Axon undergoing the process of myelination; CT, connective tissue fibrils of the Endoneurium; F, Fibroblast; M, myelinated Axon; N, Nucleus of Schwann Cell that invests many unmyelinated axons; N’, Nucleus of Schwann Cell that ensheathes one myelinated Axon; P, Perineurium. 17,600 X
The Myelin Sheath And The Synapse
Two important components of the nervous system – the Myelin Sheath that surrounds many axons and the Synapse that provides a mechanism for communication of excitation between neurons-are illustrated by electron microscopy in Figures A and B at right. Figure A is a cross section taken through a small myelinated Axon found within the spinal cord. The Axon itself (A) contains a mitochondrion (M), a few microtubules (Mt), and many Neurofilaments (Nf). In addition to providing cytoskeletal support to the Axon, the microtubules and Neurofilaments are believed to participate in the process of Axoplasmic transport described in Plate 8-2. The cell membrane of the Axon (arrow) is surrounded by a myelin sheath (MS), which when examined closely has a laminated appearance. The layers of the Myelin Sheath consist of tight, spiral wrappings of the Plasmamembrane of the Schwann Cell that surrounds the Axon. During the process of myelination, the Schwann Cell spins around the Axon and wraps it with layers of its Plasma membrane, much as a spider wraps up a fly in its web. With each successive revolution of the Schwann cell, the Cytoplasm is squeezed out from between the neighboring layers of Cell Membrane. The result of these complex maneuvers, the Myelin Sheath, is an effective electrical insulator that isolates the activities of large axons.
Whereas the Myelin Sheath is an electrical insulator, the Synapse is just the opposite: it is the site of the communication of excitation between nerve cells. Figure B is an electron micrograph of an unusual situation in which four axons (Al, A2, A3, and A4) are making synaptic contact with a single Dendrite (D). In this image, part of the Dendrite is sandwiched in between the adjacent Axonterminals, forming a series of crests of dendritic Cytoplasm (C). At the right side of the field, a single crest of dendritic Cytoplasm makes synaptic contact with two separate Axon terminals (A3, A4). Here, the fine structure of the Synapse is apparent. At the point of synaptic contact between Axon and Dendrite, the space between adjacent cell membranes is expanded to form the Synaptic Cleft. A number of synaptic vesicles (SV), filled with neurotransmitter material, are clustered within the Axon terminal near the Synaptic Cleft. When the Axon is electrically stimulated that is, when an action potential arrives at the Axon terminal – some of the membrane-limited synaptic vesicles fuse with the AxonCell Membrane and liberate their contained neurotransmitter into the Synaptic Cleft. The liberated neurotransmitter alters the electrical properties of the postsynaptic DendriteCell Membrane, thereby either exciting or inhibiting the Dendrite. In this way, neurons can “speak” to one another via chemical synapses. Not all synapses are chemical; some are electrical, centering their function around the Gap Junction, or Nexus. The Gap Junction permits certain ions to flow between adjacent cells. Since currents in nerves are carried by ions in solution, ionic continuity between cells creates electrical continuity between cells. Although electrical synapses are common, they are outnumbered by chemical synapses.
Plate 8-4, Figure A. Electron micrograph of a cross section taken through a small myelinated Axon in the spinal cord. A, Axon; MS, myelin sheath; M, mitochondrion; Mt, Microtubule; Nf, neurofilament; SV, Synaptic Vesicle in nearby nerve terminal; arrow, Plasma membrane of Axon; arrowhead, mesaxon (point at which Cell Membrane folds upon itself) of Schwann Cell. 68,000 X
Figure B. Electron micrograph of a series of synapses in the brain. Al, A2, A3, and A4, separate synaptic endings, each from a different Axon; C, crest of Dendrite Cytoplasm; D, Dendrite; M, mitochondrion; Mt, Microtubule; S, Synapse; SC, Synaptic Cleft; SV, Synaptic Vesicle. (Micrograph of “crest” Synapse courtesy of Dr. Tom Mehalick.) 57,500 X
Ganglion Cells Of The Autonomic Nervous System
The Autonomic Nervous System consists of motor neurons that participate in the regulation of a variety of “involuntary” visceral activities. Whereas the motor neurons of the peripheral nervous system innervate Skeletal Muscle fibers that power voluntary movements, the motor neurons of the Autonomic Nervous System innervate Smooth Muscle fibers that power involuntary movements of such structures as the gut, blood vessels, and sweat glands. In addition, the myoepithelial cells associated with glands such as the salivary glands are regulated by motor neurons of the autonomic nervous system.
The Autonomic Nervous System is not a system unto itself; despite its name, it does not act autonomously. Instead, its functions and its neurons are closely tied to the central and peripheral nervous systems. Many of the cell bodies of autonomic neurons reside within the Central Nervous System. Whereas the motor neurons of the peripheral nervous system are arranged so that one Motor Neuron, with its cell body in the spinal cord, transmits activity to a particular muscle, the autonomic nervous system employs two motor neurons arranged in series. The first Neuron, located in the brain or spinal cord, sends its Axon out and makes contact with the second Neuron in the series, which is usually located in a Ganglion or plexus close to the structure whose activity it mediates. An example of the second Neuron in the series, often called an autonomic Ganglion cell, is illustrated at right.
Figure A is a light micrograph of a section taken through the submaxillary Ganglion in the vicinity of the salivary glands. Here, the Ganglion cells are seen to be large cells with round, pale nuclei (N). In autonomic Ganglion cells, the prominent Nucleolus (Nu) is often placed off center. The Cytoplasm, or Perikaryon, has an abundance of Nissl substance (NS) that makes the Ganglioncells appear more dense than the nerve fibers (NF) that course past them. In the connective tissue (CT) surrounding the Ganglion, a capillary (C) is evident, as are several mast cells (M).
The same Ganglion cells are seen in greater detail in the electron micrograph in Figure B. This photomicrograph was taken of a serial thin section cut adjacent to the thick section depicted in Figure A. Here, the large, round Nucleus (N) of the Ganglion cells is mostly euchromatic; a thin ring of Heterochromatin is closely applied to the inner margin of the Nuclear Envelope. In this image, the Nissl Substance, which appeared as dense, amorphous material by light microscopy (Figure A), consists of Cisternae of the rough Endoplasmic Reticulum (RER) interspersed with thousands of free ribosomes (R). The nerve fibers (NF) that run around the Ganglion cells are small, unmyelinated fibers. Their small size becomes apparent when you notice that most of them are dwarfed by the nuclei of the Schwarm cells (SN) that ensheath them. Small, unmyelinated nerve fibers are often difficult to identify by light microscopy. Comparison of light and electron micrographs of the same bundles of small nerves, such as those depicted in Figures A and B, can facilitate the recognition of small unmyelinated nerves in histological sections.
Plate 8-5, Figure A. Light micrograph of the submandibular Ganglion of the rat. C, capillary; CT, connective tissue; M, Mast Cell; N, Nucleus of autonomic Ganglioncell Motor Neuron; NF, nerve fibers; NS, Nissl Substance; Nu, eccentrically placed Nucleolus in Ganglion cell Nucleus; SN, Schwarm cell Nucleus. 2,500 X
Figure B. Electron micrograph of serial thin section taken through the same Ganglion cells shown in Figure A. CT, connective tissue; N, Nucleus of autonomic Ganglion cell; NF, nerve fibers; R, free ribosomes; RER, rough endoplasmic reticulum; SN, Schwarm cell Nucleus. 4,000 X