I. Organization of Nervous Tissue
Nervous tissue, which is derived from neuroectoderm, is organized into two major systems:
A. Central nervous system (CNS)
B. Peripheral nervous system (PNS)
The peripheral nervous system consists of nerves that emerge from the brain stem and spinal cord:
—Cranial nerves, from the brain stem
—Spinal nerves, from the spinal cord
II. The Neuron
The structural and functional unit of the nervous system is the nerve cell or neuron. Neurons are structurally classified according to the number of cytoplasmic processes, called nerve fibers, that they possess. For example, a unipolar neuron has one fiber, a bipolar neuron has two fibers, and a multipolar neuron has several fibers. Each neuron consists of a cell body or perikaryon, from which arise the nerve fibers. And each neuron has two kinds of fibers: a single axon, which conveys nerve impulses away from the cell body, and one or more dendrites, which convey nerve impulses towards the cell body. Neurons are functionally linked by their fibers at connections called synapses. All neurons are post-mitotic.
A. The functional classification of neurons
Functionally, there are three kinds of neurons:
These neurons convey sensory information towards the CNS.
These neurons convey motor impulses away from the CNS.
interlink and coordinate activity in the other two neurons.
B. The location of neurons
Whereas the interneurons all lie within the CNS, portions of the afferent and efferent neurons project out of the CNS and constitute the nerves of the PNS. The cell bodies of afferent neurons reside in discrete structures called ganglia located near the CNS. Thus, the cell bodies of the afferent spinal nerves are located in dorsal root ganglia, present on either side of the spinal cord. Likewise, the cell bodies of the afferent cranial nerves are located in the cranial ganglia of the head. It is important to remember, however, that these ganglia are located near the CNS, but not within it.
Afferent neurons are essentially bipolar, or more correctly speaking, pseudounipolar. One process or fiber extends from the cell body in the ganglion into the CNS (i.e., the central fiber). The other fiber extends from the cell body in the ganglion to peripheral regions of the body (i.e., the peripheral fiber). The peripheral fiber receives sensory input and transmits this information back to the ganglion. This impulse then continues along the central fiber into the CNS. The cell bodies of efferent neurons, on the other hand, all lie within the CNS. The axons of these neurons leave the CNS and innervate skeletal muscle.
C. The reflex arc of neurons
An example of the interaction between afferent and efferent neurons is illustrated by a neural pathway called the reflex arc.
—The knee jerk response
Stretching the patellar tendon with a soft hammer blow stimulates afferent nerve endings in the muscle spindle. The sensory impulse that is generated here travels along afferent fibers to cell bodies located in a dorsal root ganglion and from there to the spinal cord. Within the spinal cord, the afferent fibers synapse on the cell bodies of efferent neurons, whose long axons extend to innervate muscles in the leg. Motor impulses are then conveyed down these efferent fibers to cause muscle contraction, thereby eliciting a reflex jerk. This is an example of a monosynaptic pathway involving only two neurons. Usually, more than two neurons are involved and such a pathway is said to be polysynaptic. In most neural pathways, there are several interneurons interposed between the central portions of the afferent and efferent neurons.
D. Neuronal structure
Most neurons in the CNS are multipolar with many dendrites. The large nucleus contains a prominent nucleolus and abundant euchromatin. Basophilic structures in the cytoplasm of the cell body and dendrites are called Nissl bodies. These bodies represent large numbers of ribosomes, both free and attached (i.e., much protein synthesis is occurring). Neurons contain numerous microtubules (neurotubules) and intermediate filaments (neurofilaments). These provide structural support to the neuron and help maintain its characteristic shape. The microtubules also provide a means of intracellular transport, acting as "railroad tracks" that guide the movement of materials within the cell. Because neurons are post-mitotic, they tend to accumulate "wear-and-tear" pigments called lipofuscin.
The longest nerve fiber is the singular axon, which may give off a number of collateral branches. The part of the cell body from which the axon emerges is called the axon hillock. This region and the axon itself are devoid of Nissl bodies. The cell membrane covering the axon is termed the axolemma, and the cytoplasm inside is called the axoplasm. Axons contain many neurotubules and neurofilaments, and the smooth endoplasmic reticulum here is referred to as the axoplasmic reticulum. In a myelinated axon, the axon is wrapped with numerous concentric layers of cell membrane forming a myelin sheath. The cell membrane forming this sheath is provided by a non-neuronal cell, such as the oligodendrocyte discussed below. Not all axons are myelinated, however. Some are unmyelinated.
Since the axon lacks a rough endoplasmic reticulum, proteins must be synthesized in the cell body and transported down the axon in a process called axoplasmic transport (anterograde transport). There are both fast and slow components to this transport. The fast component (~200 mm/day) transports neurotransmitter-filled vesicles and other membranous components that are needed for synaptic transmission at the axon terminals. The slow component (~2 mm/day) transports some enzymes and other proteins that are needed for general axonal growth and maintenance.
In addition to anterograde transport from the cell body to the nerve terminals, the axon exhibits retrograde transport of material in the reverse direction. This process enables the neuron to recycle membrane that would otherwise accumulate in the axolemma of the axon terminal during sustained release of neurotransmitter. To retrieve accumulated membrane, vesicles are formed in the terminals by endocytosis and transported back to the cell body for lysosomal digestion. This type of transport is clinically important because viruses can be transported from infected tissues to the CNS by this mechanism.
The neurotubules play a key role in these axoplasmic transport processes, though the exact nature of their involvement is not well understood. But in essence, movement along the neurotubules is thought to involve the microtubule-associated proteins (MAPs) kinesin and dynein. These “molecular motors” interact with the neurotubules in such a way as to “pull” their cargo along the length of the axon. Kinesin is responsible for anterograde transport and dynein is responsible for retrograde transport.
Dendrites are branched fibers, generally much shorter than the axon. Their surfaces are covered with numerous small processes called dendritic spines, which provide a large surface area for receiving nerve impulses from neighboring neurons. Like axons, dendrites can transport substances to or from the cell body. Unlike axons, however, dendrites contain Nissl bodies.
E. The nerve impulse
When a neuron is not conducting a nerve impulse, its membrane is polarized; that is, it carries a transmembrane potential. This means that the inside of the neuron is negative, i.e., has a net negative charge, relative to the outside, which is more positive. The resting potential, as it is called, is about -70 mV.
This membrane potential is due to a higher concentration of negative ions within the neuron and a higher concentration of positive ions outside the neuron. The high concentration of negative ions is due principally to nondiffusible macromolecules that carry a net negative charge (e.g., polyanionic proteins and nucleic acids). The charge separation is maintained through the activity of the sodium-potassium pump, which uses the energy obtained from ATP hydrolysis to pump potassium ions (K+) into the neuron and pump sodium ions (Na+) out of the neuron. However, because more Na+ is pumped out of the neuron than K+ pumped in, and because the K+ tends to diffuse back out of the neuron, the cytoplasm has a deficit of positive charges to balance the negative charges present. This is how the inside of the neuron is able to maintain itself negative relative to the outside.
It should be remembered that the sodium-potassium pump works against the concentration gradients exhibited by these two cations. Thus, Na+ is normally at a higher concentration outside the neuron than within, and the reverse is true of K+. The pump must therefore work against the natural tendency of these cations to diffuse along their concentration gradients, i.e., from regions of high concentration to regions of low concentration.
When a neuron receives an appropriate stimulus, the first thing that happens is that there is a massive influx of Na+ due to an opening of Na+ channels in the membrane. This influx of positive charges neutralizes the negative charges present and destroys the resting potential that was present before the stimulus, i.e., the membrane is depolarized. In fact, so many positive charges rush into the cytoplasm that the inside of the neuron becomes temporarily positive relative to the outside.
Shortly after the Na+ influx, there is a similar efflux of K+ due to the opening of K+ channels. Because the interior of the neuron is now losing positive charges, the membrane potential begins to be restored, i.e., the membrane becomes repolarized. Actually, the loss of K+ is so great that the inside of the neuron is temporarily more negative than normal, i.e., the membrane is hyperpolarized.
While these ion fluxes are occurring, the sodium-potassium pump is continuing to operate, pumping Na+ out and pumping K+ in. Shortly after the K+ efflux, the pump restores the normal charge separation of the resting potential. This entire sequence of events is called the action potential. A wave of depolarization that travels from one end of a nerve fiber to the other is called a nerve impulse.
In unmyelinated axons, the entire axolemma is involved in the propagation of a nerve impulse. However, in myelinated axons, only the unmyelinated regions of the axon (nodes of Ranvier) undergo depolarization. This is because myelin acts as an electrical insulator and prevents the flow of current across the axolemma. Therefore, the wave of depolarization "jumps" from one node to the next in a process called saltatory conduction. This is a much faster mode of conduction than that exhibited by unmyelinated axons.
F. The synapse
Nerve impulses are transmitted from one neuron to the next at sites called synapses. Most synapses are chemical synapses, which means that they transmit an impulse in one direction only through the action of neurotransmitters. Electrical synapses are basically gap junctions through which ions freely pass in either direction. Conjoint synapses represent a combination of the two.
The part of the neuron that delivers the impulse at the synapse is the presynaptic terminal, whereas the part of the neuron that receives the impulse is the postsynaptic terminal. The presynaptic terminal is present at the ends of axons (axon terminals). The synapse consists of a specialized region of the cell membrane of the axon terminal (presynaptic membrane), which is closely applied to the cell membrane of an adjoining cell body, dendrite, or axon (postsynaptic membrane). Between the pre- and postsynaptic membranes is a narrow synaptic cleft. The axon terminal contains numerous mitochondria and synaptic vesicles filled with neurotransmitter.
When a wave of depolarization reaches the axon terminal, it causes Ca++ channels to open in the axolemma, resulting in Ca++ influx into the axon terminal. This induces the exocytosis of the synaptic vesicles, which discharge their contents into the synaptic cleft. The released neurotransmitter then combines with receptors on the postsynaptic membrane. Depending on the type of neurotransmitter involved, this interaction results in either membrane depolarization or hyperpolarization. Thus, a neurotransmitter can exert either excitatory or inhibitory effects. Whether or not a neuron becomes sufficiently depolarized to conduct an action potential is determined by the sum total of the excitatory and inhibitory signals it receives.
As mentioned earlier, the accumulation of excess cell membrane at the axon terminal is prevented by membrane recycling, whereby vesicle membrane added to the axolemma during exocytosis is retrieved through endocytosis. The coated vesicles thus formed have two possible fates. They can return to the cell body for lysosomal digestion or, in some instances, they can fuse with a large membranous cisterna from which new synaptic vesicles are subsequently produced.
III. The Central Nervous System
The neurons constituting the CNS are not supported by connective tissue. Rather, specialized glial cells provide support for the nerve cell bodies and their fibers. They also provide other functions, as we will see. Within the CNS, aggregations of nerve cell bodies are referred to as nuclei, which are analogous to the ganglia of the PNS. Bundles of nerve fibers within the CNS are referred to as tracts, which are analogous to the nerves of the PNS.
A. The spinal cord
The brain and spinal cord are each divided into two major components known as gray and white matter.
Gray matter consists principally of the cell bodies of efferent neurons and associated glial cells or neuroglia. These cell bodies are surrounded by a tangled mass of nerve fibers and glial processes, collectively referred to as the neuropil. In the spinal cord, the gray matter is organized into anterior (ventral) and posterior (dorsal) horns, which are continuous columns of cells extending the length of the spinal cord.
Surrounding the gray matter is the white matter, which lacks neuronal cell bodies. It contains bundles of nerve axons, running the length of the spinal cord, that originate from neuronal cell bodies in the gray matter. Although the white matter does not contain any neuronal cell bodies, it does contain many glial cells. One type of glial cell, the oligodendrocyte, is responsible for forming myelin sheaths around axons in the white matter. Essentially, each oligodendrocyte wraps a portion of an axon with several concentric layers of one of its cytoplasmic processes. The myelin sheath thus formed is not continuous along the length of the axon, but is interrupted at intervals called nodes of Ranvier. The ensheathed segments between the bare nodes are called internodes.
B. The brain
In much of the brain, the relative positions of white and gray matter are reversed as compared to their positions in the spinal cord. Hence, the outer layer of the cerebral hemispheres and cerebellum consists of gray matter, which covers the white matter beneath.
The cerebral cortex
The outer layer of the cerebrum, called the cortex, is convoluted into folds and fissures referred to as gyri and sulci, respectively. In general, the cell bodies of the cortical neurons are arranged in six layers:
This is the most superficial layer. It contains few cell bodies, but many nerve fibers from neurons in underlying layers.
—Outer granular layer
This layer contains the cell bodies of small neurons.
This layer contains large, pyramid-shaped neuronal cell bodies.
—Inner granular layer
This layer contains more cell bodies of small neurons.
—Inner pyramidal (ganglionic) layer
This layer contains more pyramid-shaped neuronal cell bodies. In the part of the cortex responsible for motor control, the pyramidal cells in this layer are very large and are called Betz cells.
—Polymorphic (multiform) layer
This is the lowermost layer. It contains cell bodies with a variety of different shapes.
The cerebellar cortex
In contrast to the cerebrum, the cortex of the cerebellum has only three layers:
This is the most superficial layer and is similar to the molecular layer in the cerebral cortex.
This layer contains the cell bodies of large Purkinje cells, which are characterized by an extensive system of branching dendrites.
This is the
lowermost layer and is similar to the granular layers in the cerebral cortex.
The neuroglia provide a supportive role to the neurons of the CNS. There are four types of neuroglia: (1) oligodendrocytes, (2) astrocytes, (3) microglia, and (4) ependymal cells.
Within the white matter of the CNS, the cytoplasmic processes of oligodendrocytes form concentric wrappings around axons. Each such wrapping constitutes an internodal segment of a myelin sheath. Because each oligodendrocyte has several processes, it can form myelin on several different axons.
Astrocytes are star-shaped cells. Some of their numerous processes attach to capillaries, others attach to neurons. Thus, they are interposed between capillaries and neurons. Their foot processes almost completely cover the surface of capillaries. There are two types of astrocytes: (1) Fibrous astrocytes in the white matter, and (2) protoplasmic astrocytes in the gray matter. In addition to their supportive function, astrocytes are thought to regulate the ionic composition of the extracellular environment, and regulate the exchange of nutrients and metabolites between blood and neuron. Also, astrocytes form scar tissue when the CNS is injured. They react to injury by proliferating in a process called gliosis. Astrocytes contain intermediate filaments composed of glial fibrillary acidic protein (GFAP), the presence of which can be used to distinguish astrocytes from other glial cells and neurons.
Microglia are small cells distributed throughout the gray and white matter. They can transform into active macrophages in response to CNS damage.
Ependymal cells cover the choroid plexuses, as well as line the ventricles of the brain and the central canal of the spinal cord. They constitute a simple cuboidal epithelial membrane called the ependyma, the free surface of which exhibits cilia and microvilli.
D. The meninges
meninges are the connective tissue coverings of the brain and spinal
This layer is applied to the outer surface of the brain and spinal cord. It consists primarily of a simple squamous epithelium and associated connective tissue fibers. The blood vessels nourishing the brain and spinal cord are most abundant in this layer. The capillaries here have zonula occludens junctions, which form the basis of the blood-brain barrier.
This layer is situated above the pia. Joining the two layers are numerous strands or trabeculae of delicate connective tissue. The space between the pia and arachnoid is called the subarachnoid space, which is filled with cerebrospinal fluid. The arachnoid consists of connective tissue fibers covered by simple squamous epithelia.
This outermost layer is made of dense fibrous connective tissue. In the skull, the dura is continuous with the periosteum of the cranial vault. The potential space between the arachnoid and dura is called the subdural space. Similarly, the potential space between the dura and the bone of the cranium or vertebral canal is called the epidural space.
Peripheral Nervous System
A. Components of the PNS
peripheral nervous system is composed of the following:
Ganglia contain the cell bodies of neurons:
—Cranial and spinal ganglia
These ganglia contain the cell bodies of cranial and spinal afferent (sensory) neurons.
These ganglia contain the cell bodies of efferent (motor) neurons of the autonomic nervous system.
Nerves contain the axons of both afferent and efferent neurons:
—Cranial nerves, originating from the brain stem
nerves, originating from
the spinal cord
Axons terminate in specialized structures:
—Afferent nerve endings
These are sensory nerve endings, specialized for different sensory modalities (e.g., pain, heat, etc.).
—Efferent nerve endings
motor nerve endings that innervate muscles and glands.
B. Spinal ganglia
As noted earlier, the dorsal root ganglia contain the cell bodies of afferent neurons. These cell bodies are surrounded by a layer of satellite or capsule cells, which are the PNS equivalents of the neuroglia found in the CNS. Each neuronal cell body gives off two fibers. One fiber passes centrally into the gray matter of the spinal cord, the other exits through the dorsal root of a spinal nerve. This branch terminates at a receptor ending in the periphery. Both branches have the structural characteristics of myelinated axons, even though the peripheral branch conducts impulses towards the cell body like a dendrite. Nevertheless, both fibers are considered axons.
C. Peripheral nerves
Unlike the CNS, the nerves of the PNS contain supportive layers of connective tissue:
—Epineurium, surrounds entire nerve. This layer contains small blood vessels, the vasa nervorum.
—Perineurium, surrounds fascicles (bundles) of nerve fibers.
—Endoneurium, surrounds individual nerve fibers. This layer is in contact with the basement membrane around the nerve fiber.
Within the endoneurium, each axon is invested by a myelin sheath. The myelin sheath that covers axons in the PNS is derived from Schwann cells, which wrap around an axon in much the same way as the oligodendrocytes do in the CNS. However, whereas each oligodendrocyte can form an internode on several different axons, each Schwann cell can form only one internode on a single axon. Another difference between CNS and PNS myelin is that, in peripheral nerves, there are small defects in the myelin called clefts of Schmidt-Lantermann. These are small pockets of Schwann cell cytoplasm trapped in the myelin.
Some afferent fibers and autonomic efferent fibers have no myelin sheath. These nerve fibers are nevertheless supported by Schwann cells. Unmyelinated axons are held in small invaginations of the Schwann cell surface. Many such Schwann cells arranged end-to-end provides a supporting sheath for the unmyelinated axons.
D. Response to injury
When an axon is transected, the distal segment of the axon and its myelin sheath degenerate. Phagocytic cells remove most of the debris, but remnants of the endoneurial sheath and a few Schwann cells often leave a tubular pathway back to the innervated tissue. On the proximal side of injury, the perikaryon swells and exhibits chromatolysis (dissolution of Nissl substance). The nucleus migrates to the periphery and several neurites grow out of the proximal axon stump. Proliferating Schwann cells bridge the gap across the injury site. A neurite may then grow across the scar and enter the endoneural tube, eventually re-connecting with the peripheral target tissue.
V. The Autonomic Nervous System
The efferent innervation of cardiac muscle, smooth muscle, and glands is via the ANS (involuntary control). This is in contrast to the efferent innervation of skeletal muscle by cranial and spinal nerves (voluntary control). The ANS constitutes part of the larger PNS. The remainder of the PNS is often referred to as the somatic nervous system.
A. Divisions of the autonomic nervous system
There are two divisions of the ANS:
—The sympathetic division ("fight or flight")
—The parasympathetic division ("feed or fornicate")
Each division of the ANS communicates with the CNS. Moreover, each division innervates the peripheral target tissue (i.e., cardiac muscle, smooth muscle, or glands) with two efferent neurons: (1) a preganglionic neuron whose cell body resides within the CNS, and (2) a postganglionic neuron whose cell body resides in an autonomic ganglion located outside the CNS.
B. The sympathetic division
The cell bodies of preganglionic sympathetic neurons are located in the gray matter of the thoracolumbar region of the spinal cord. Their axons leave the CNS via spinal nerves and synapse with postganglionic nerve cell bodies located in sympathetic ganglia near the spinal cord (prevertebral and paravertebral ganglia). The axons of these postganglionic neurons then leave the ganglia and innervate peripheral tissues. The neurotransmitter released from the axon terminals of preganglionic nerves is acetylcholine, whereas that released from postganglionic axon terminals is norepinephrine.
C. The parasympathetic division
The cell bodies of some preganglionic parasympathetic neurons are located in the gray matter of the brain stem. Their axons leave the CNS via cranial nerves. The cell bodies of the other preganglionic neurons are located in the gray matter of the sacral region of the spinal cord. Their axons leave the CNS via spinal nerves. Therefore, the parasympathetic division is also called the craniosacral division, in contrast to the thoracolumbar (sympathetic) division. The axons of the preganglionic neurons synapse with postganglionic nerve cell bodies located in head ganglia or in terminal ganglia located near the target tissue. The axons of these postganglionic neurons then leave the ganglia and innervate the target tissue. The neurotransmitter released from both pre- and postganglionic axon terminals is acetylcholine.