I. General Features of Nerve Tissue & the Nervous System
Nerve tissue consists of neurons that transmit electrochemical impulses and the supporting cells that surround them. It contains little extracellular material.
Neurons (II). These cells are specialized to receive, integrate, and transmit electrochemical messages. Each has a cell body, also called the soma (“body”) or perikaryon (“around the nucleus”), comprising the nucleus, the surrounding cytoplasm, and the plasma membrane. Each neuron has a variable number of dendrites (cytoplasmic processes that collect incoming messages and carry them toward the soma) and a single axon (a cytoplasmic process that transmits messages to the target cell). Axons of most neurons have a myelin sheath formed by supporting cells and interrupted by gaps called nodes of Ranvier. Axon segments between the gaps are called internodes.
Supporting cells (III) are called neuroglia (“nerve glue”) or glial cells. Their functions include structural and nutritional support of neurons, electrical insulation, and enhancement of impulse conduction velocity (VII.B.2 and 5).
Signals (impulses) are propagated as a wave of depolarization along the plasma membrane of the dendrites, soma, and axon. Depolarization involves channels (ionophores) in the membrane, which allow ions (e.g., Na+, K+) to enter or exit the cell. In unmyelinated axons, depolarization occurs in waves over the entire surface. In myelinated axons, depolarization occurs only at nodes of Ranvier, jumping from node to node (saltatory conduction). Impulse conduction is therefore faster in myelinated axons.
Signals pass from neuron to target cell by specialized junctions called synapses. A target may be another neuron or a cell in the end-organ (e.g., gland or muscle). At chemical synapses (IV), signals are transmitted by the exocytosis of neurotransmitters—chemicals such as acetylcholine that cross a narrow gap (synaptic cleft) between cells to initiate target cell depolarization. At the less common electrical synapses, signals are transmitted by ions flowing through a gap-junction–like complex.
D. Subsystems of the Nervous System
The nervous system comprises two overlapping pairs of subsystems.
The central and peripheral nervous systems are defined mainly by location. The central nervous system (CNS) includes the brain and spinal cord. The peripheral nervous system (PNS) includes all other nerve tissue. See Table 9–1 for terminology associated with the CNS and PNS and structural comparisons.
The autonomic and somatic nervous systems are defined according to function but also have distinctive anatomic features. Each has CNS and PNS components. The autonomic nervous system (ANS; Fig. 9–1) controls involuntary visceral functions (e.g., glandular secretion, smooth muscle contraction) and has both motor and sensory pathways, although visceral sensory pathways typically are not considered part of the ANS. Each motor pathway consists of two neurons that synapse in a peripheral autonomic ganglion (V; Fig. 9–1). The cell body of the first (preganglionic) neuron is in the CNS; the cell body of the second (postganglionic) neuron is in the autonomic ganglion. The cell bodies of the sensory neurons are in craniospinal ganglia (V) and have processes that extend centrally and peripherally. The ANS is subdivided into the sympathetic and parasympathetic nervous systems, whose structure and functions are compared in Table 9–2. When they innervate the same end-organ, sympathetic and parasympathetic nerves usually have opposing effects. The somatic nervous system includes all nerve tissue except that of the ANS. It controls somatosensory perception (e.g., touch, heat, cold) and somatomotor (voluntary) functions (e.g., skeletal muscle contraction). Acetylcholine is the most common somatic neurotransmitter.
E. Embryonic Development of Nerve Tissues (Fig. 9-2)
All neurons and supporting cells derive from ectoderm. Cells of the early embryo's midline dorsal ectoderm are induced by the underlying notochord to form a thickened neural plate. The plate's lateral border thickens and the center invaginates, forming a troughlike neural groove. As the groove deepens, the lateral borders contact each other to close the groove and form the neural tube. Cells lining the tube elongate to form a mitotically active pseudostratified columnar epithelium (neuroepithelium), and they eventually form the layers that generate the entire CNS. As the neural groove closes, cells at its lateral borders proliferate to form two columnar masses that come to lie dorsal to the neural tube and form the neural crest. Neural crest cells migrate away from the neural tube and form the PNS, including the sensory neurons of the craniospinal ganglia (V), the postganglionic neurons of the ANS, the Schwann cells of peripheral nerves, and the satellite cells of ganglia. Neural crest cells also form the meninges (I.G) and the craniofacial mesenchyme. Neural crest derivatives described in other chapters include the odontoblasts of developing teeth (15.III.C.5.b and E), the skin's melanocytes (18.II.B.2), and the adrenal medulla's chromaffin and ganglion cells (21.II.B.1 and 2).
Mature neurons are generally incapable of mitosis and are often used as examples of terminally differentiated cells. Aging neurons may contain abundant lipofuscin pigment. The inability of neurons to divide makes repair of nerve tissue more difficult than repair of most other tissues. Neuron cell bodies lost through injury or surgery cannot easily be replaced, but if an axon is severed or crushed and the cell body remains intact, axonal regeneration is possible (VIII). Supporting cells, unlike mature neurons, can divide if stimulated by injury. Recent advances in stem cell biology are raising hopes for improved repair of damaged neural tissue and neuronal replacement. Approaches include activating or recruiting endogenous stem cells or providing exogenous stem cells.
The brain and spinal cord are separated from the bony compartments housing them (skull and vertebral canal) by three connective tissue layers termed the meninges. The outer layer, or dura mater, is dense connective tissue bound tightly to the periosteum of the surrounding bone. The middle layer, or arachnoid, has two components: (1) a layer of loose connective tissue in contact with the dura mater and (2) many connective tissue strands (trabeculae) attaching the arachnoid to the underlying pia mater. The spaces between the arachnoid trabeculae contain cerebrospinal fluid. Projections of the arachnoid into sinuses in the dura are called arachnoid villi. The innermost layer, or pia mater, is a thin, richly vascularized layer of loose connective tissue that is firmly attached to the surface of the brain or spinal cord but is separated from the neurons by neuroglial cell processes. Ramified, cuboidal epithelium-covered projections of the pia mater into the brain's ventricles are collectively termed the choroid plexus; they produce the cerebrospinal fluid by selective ultrafiltration of blood plasma.
CNS tissue receives oxygen and nutrients from capillaries in the pia mater. These capillaries are relatively impermeable because (1) their endothelial cells lack fenestrations and are joined at their borders by tight junctions and (2) they are surrounded by the cytoplasmic processes of neuroglia called astrocytes (III.A.1). These features contribute to a structural and functional barrier that protects CNS neurons from many extraneous influences and prevents certain antibiotics and chemotherapeutic agents from reaching the CNS.
Table 9–1. Comparisons of Central and Peripheral Nervous Systems and Associated Terminology. ||Download (.pdf)
Table 9–1. Comparisons of Central and Peripheral Nervous Systems and Associated Terminology.
Central Nervous System
Peripheral Nervous System
Brain and spinal cord
Peripheral nerves, ganglia, and nerve plexuses
Term(s) for collections of nerve cell bodies
Gray matter (groups of cell bodies in gray matter are called nuclei)
Ganglia (V) (e.g., spinal or dorsal root ganglia and sympathetic ganglia)
Term for collections of myelinated axons
Types of supporting cells present
Astrocytes, oligodendrocytes, microglia, and ependymal cells
Schwann cells and satellite cells
Cell type that forms myelin
Supporting cell type that invests unmyelinated fibers
Table 9–2. Comparisons of Motor Pathways of the Sympathetic and Parasympathetic Divisions of the Autonomic Nervous System. ||Download (.pdf)
Table 9–2. Comparisons of Motor Pathways of the Sympathetic and Parasympathetic Divisions of the Autonomic Nervous System.
Sympathetic Motor Pathways
Parasympathetic Motor Pathways
Location of cell bodies of preganglionic motor neurons
Thoracolumbar outflow: intermediolateral cell column of spinal cord gray matter in spinal segments T1 to L3
Craniosacral outflow: cranial division—medulla and midbrain nuclei; axons exit CNS through cranial nerves III, VII, IX, and X; sacral division—intermediate gray matter of sacral spinal cord
Relative length of preganglionic axons
Short (some preganglionic fibers extend to adrenal medulla and are thus longer)
Typical preganglionic neurotransmitter
Location of cell bodies of postganglionic motor neurons
Sympathetic chain ganglia (close to spinal column)
Intramural ganglia and other ganglia close to target organs
Relative length of postganglionic axons
Typical postganglionic neurotransmitter
Epinephrine or norepinephrine
Schematic diagram of autonomic motor pathways. Note that the sympathetic (thoracolumbar) outflow involves short preganglionic and long postganglionic fibers, whereas the parasympathetic (craniosacral) outflow involves long preganglionic and short postganglionic fibers.
The cell body (soma, perikaryon) is the neuron's synthetic and trophic center. It receives signals from axons of other neurons through synaptic contacts on its plasma membrane and subsequently relays them to its axon. The nucleus typically is large, central, and euchromatic. It has a prominent nucleolus and heterochromatin around the nuclear envelope's inner surface. The soma's cytoplasm contains many organelles, including mitochondria, lysosomes, and centrioles. The abundant free and RER-associated polyribosomes appear as basophilic clumps collectively called Nissl bodies. The well-developed Golgi complex packages neurotransmitters in neurosecretory, or synaptic, vesicles. Once packaged, the vesicles are transported by molecular motor proteins along microtubules (neurotubules) through the axon to the terminal bouton (II.C). Neurotubules and bundles of neurofilaments (intermediate filaments) are found throughout the perikaryon and extend into the axon and dendrites.
These extensions of the soma increase the surface available for incoming signals. The farther they are from the soma, the thinner they are, owing to successive branching. Much of their surface may be covered with synaptic contacts, and some have sharp projections, termed dendritic spines, or gemmules, that act as synaptic sites. Dendrites lack Golgi complexes but contain small amounts of other organelles found in the perikarya.
Each neuron has one axon, a complex cell process that carries impulses away from the soma. An axon is divisible into several regions. The axon hillock, the part of the soma leading into the axon, differs from the rest of the perikaryon in that it lacks Nissl bodies. An entire axon is usually not visible in sectioned material, but its origin is often distinguishable from that of dendrites by the absence of Nissl-related basophilia. The initial segment is the part of a myelinated axon between the axon hillock's apex and the beginning of the myelin sheath. It is characterized by a thin layer of electron-dense material, or dense undercoating, beneath the plasma membrane, and it contains neurotubule and neurofilament bundles originating in the axon hillock. The axon proper is the axon's main trunk. Unlike dendrites, the axon diameter tends to be constant along its entire length. The larger an axon's diameter, the more likely it is to be myelinated and the higher its rate of impulse conduction. Some axons have branches, termed collaterals, that may contact other neurons or even return to the soma of origin to modulate their own subsequent depolarization. The axoplasm (cytoplasm) contains few organelles other than some mitochondria and parallel bundles of neurotubules and neurofilaments. It has limited metabolic activity, but it conveys metabolic products to and from the axon terminals (VII.A). Signal transmission (VII.B) relies heavily on the asymmetric ion distribution (potential differences) on either side of the axolemma, the axonal plasma membrane. Many axons undergo branching (arborization) near their terminations. The degree of terminal arborization depends on axon size and function. Each terminal branch ends in an enlargement called a terminal end-bulb or terminal bouton. Swellings in an axon's wall before its termination are termed boutons en passage. Each bouton contains many mitochondria and neurosecretory vesicles. A specialized region of its plasma membrane, the presynaptic membrane, forms part of a synapse (IV).
D. Classification of Neurons
Overlapping classifications describe the wide variety of neurons in terms of their structure and function (Table 9–3).
Table 9–3. Classification of Neuron Types. ||Download (.pdf)
Table 9–3. Classification of Neuron Types.
Types and Description
Configuration of cell processes
Multipolar: most abundant; two or more dendrites radiating in many directions; those of Purkinje cells extend in flat, fanlike array
Motor neurons of ventral horn of spinal cord gray matter, pyramidal cells of cerebral cortex, and Purkinje cells of cerebellar cortex
Bipolar: single dendrite arising from pole of soma opposite the axon; special sensory function
Retina, olfactory mucosa, and cochlear (spiral) and vestibular ganglia of inner ear
Pseudounipolar: single T-shaped process; both branches of T resemble axons in structure and function; impulses are carried only by processes, bypassing the soma; general sensory function
Sensory neurons of dorsal root and in most cranial ganglia; begin in embryo as bipolar neurons; axon and dendrite subsequently fuse
Unipolar: single short axon and no dendrites
Photoreceptor cells (rods and cones; 24.V.E.1)
Golgi type I: large soma and long axon
Motor neurons of spinal cord and pyramidal cells of cerebral cortex
Golgi type II: small soma and short axon that undergoes extensive terminal arborization close to soma
Interneurons of the spinal cord
Motor neurons: carry impulses to end-organs; induce or inhibit muscle contraction and glandular secretion; both somatic and autonomic systems have motor components
Multipolar neurons of spinal cord gray matter and autonomic ganglia; pyramidal cells of cerebral cortex; Purkinje cells of cerebellar cortex
Sensory neurons: receive impulses generated by stimulation of peripheral sensory cells and organs and carry them toward central nervous system
Bipolar neurons of special sensory ganglia, pseudounipolar neurons of craniospinal ganglia, and unipolar neurons (rods and cones) of retina
Interneurons: carry signals between (1) motor neurons, (2) sensory neurons, and (3) motor and sensory neurons
Golgi type II neurons in brain and spinal cord that coordinate neural activity and mediate reflexes
Cholinergic neurons release acetylcholine
Most somatic motor neurons (at neuromuscular synapses) and parasympathetic motor neurons
Adrenergic and noradrenergic neurons release adrenaline (epinephrine) and noradrenaline (norepinephrine), respectively
Most postganglionic sympathetic motor neurons
GABAergic neurons release GABA, an inhibitory neurotransmitter
Some neurons of cerebellum, cerebral cortex, and hippocampus
Dopaminergic neurons release dopamine
Some hypothalamic neurons (20.III.E.2)
Serotonergic neurons release serotonin (5-hydroxytryptamine)
Parasympathetic neurons in gut and pineal gland
Glycinergic neurons release glycine
Some neurons of spinal cord
By providing neurons with structural and functional support, these cells play a more indirect role in neural activity. Positioned between the blood and the neurons, they define compartments and monitor materials passing between them. It is difficult to maintain neurons in tissue culture without supporting cells. As indicated in Table 9–1, different supporting cell types are found in the CNS and PNS.
A. Supporting Cells of the CNS
There are approximately 10 neuroglial cells per neuron in the CNS. Glial cells are typically smaller than neurons. Their processes, although abundant and extensive, are indistinguishable without special stains. Identification is based on nuclear morphology. The supporting cells in the CNS are the macroglia (astrocytes and oligodendrocytes), the microglia, and ependymal cells.
Astrocytes are the largest glial cells. Their nuclei, also the largest, are irregular, spherical, and pale-staining, with a prominent nucleolus. Their branching cytoplasmic processes are tipped by vascular end-feet; these surround capillaries of the pia mater and are important components of the blood–brain barrier (I.H). Protoplasmic astrocytes (mossy cells) are more common in gray matter. They have ample granular cytoplasm and short, thick, highly branched processes. Fibrous astrocytes are more common in white matter. Silver stains reveal fibrous material in their cytoplasm. Their long, thin processes are less branched than those of protoplasmic astrocytes.
Oligodendroglia or oligodendrocytes, the most numerous glial cells, occur in both gray and white matter. The size and staining intensity of their spherical nuclei are intermediate between those of the astrocytes and microglia. Like the Schwann cells of the PNS, oligodendrocytes form myelin and occur in rows to myelinate entire axons. Unlike a Schwann cell, each may provide myelin for segments of several axons. Unmyelinated axons of the CNS are not sheathed (compare with III.B.1).
Microglia, the smallest and rarest of the glia, occur in both gray and white matter. Their nuclei are small and often bean-shaped, and their chromatin is so condensed that they often appear black in H&E–stained sections. Their processes are shorter than those of astrocytes and are covered with thorny branches. Microglial cells may derive from mesenchyme, or they may be glioblasts (immature oligodendrocytes) of neuroepithelial origin. Some microglia are components of the mononuclear phagocyte system and have phagocytic capabilities. When neural injury is unaccompanied by vascular injury, phagocytic cells in the lesioned area appear to derive from macroglia.
Ependymal cells derive from ciliated neuroepithelial cells lining the neural tube (I.E). In adults, they retain their epithelial nature and some cilia and line the neural tube derivatives (the brain's ventricles and aqueducts and the spinal cord's central canal). The lining resembles a simple columnar epithelium, but ependymal cells have basal cell processes extending deep into the gray matter. The ependymal lining is continuous with the cuboidal epithelium of the choroid plexus (I.G).
B. Supporting Cells of the PNS
Schwann cells are the supporting cells of peripheral nerves. One Schwann cell may envelop segments of several unmyelinated axons or provide a segment of a single myelinated axon with its myelin sheath. Each myelinated axon segment is surrounded by multiple layers of a Schwann cell process with most of its cytoplasm squeezed out; the multilayered Schwann cell plasma membrane, called myelin, consists mainly of phospholipid. Gaps between the myelin sheath segments are the nodes of Ranvier. Ovoid or flattened Schwann cell nuclei lie peripheral to the axon they support. They are larger and more euchromatic than the fibrocyte nuclei scattered among the axons.
Satellite cells are specialized Schwann cells in craniospinal and autonomic ganglia (V), where they form a one-cell-thick covering over the cell bodies of the neurons (ganglion cells). Their nuclei are spherical, with mottled chromatin. In sections, the nuclei typically appear as a “string of pearls” surrounding the much larger ganglion cell bodies.
Synapses are specialized junctions by means of which stimuli are transmitted from a neuron to its target cell. Artificially stimulated axons can propagate a wave of depolarization in either direction, but the signal can travel in only one direction across a synapse, which functions as a unidirectional signal valve. Synapses are named according to the structures they connect (e.g., axodendritic, axosomatic, axoaxonic, and dendrodendritic). The three major structural components of each synapse are the presynaptic and postsynaptic membranes and the synaptic cleft between them (Fig. 9–3).
This is the part of the terminal bouton membrane closest to the target cell. It includes an electron-dense thickening into which many short intermediate filaments insert, as in a hemidesmosome. In response to stimulation, neurosecretory vesicles in the bouton fuse with the presynaptic membrane and exocytose their neurotransmitters into the synaptic cleft. SNAREs are required for vesicle binding to the presynaptic membrane. Neurosecretory vesicles occur only in the presynaptic component of the junction. Vesicle membrane added to the presynaptic membrane is recycled by pinocytosis lateral to the synaptic cleft. Intact vesicles do not cross the cleft.
B. Synaptic Cleft (Synaptic Gap)
This is a fluid-filled space, generally 20-nm wide, between the presynaptic and postsynaptic membranes. It is shielded from the rest of the extracellular space by supporting cell processes and basal lamina material that binds the presynaptic and postsynaptic membranes together. Some clefts are traversed by dense filaments that link the membranes and perhaps guide neurotransmitters across the gap.
This thickening of the plasma membrane of the target cell (e.g., neuron or muscle) resembles the presynaptic membrane but also contains receptors for neurotransmitters. When enough receptors are occupied, transmitter-gated ion channels (2.II.C.2.a) open, depolarizing the postsynaptic membrane (VII.B.2). Neurotransmitter (e.g., acetylcholine) remaining in the cleft after stimulating the postsynaptic neuron (or other target cell) is degraded by enzyme (e.g., acetylcholinesterase) in the cleft. Degradation products undergo endocytosis by coated pits (2.II.C.3.c) in the bouton membrane, lateral to the presynaptic thickening. Removal of excess transmitter allows the postsynaptic membrane to reestablish its resting potential and prevents continuous activation of the target cell in response to a single stimulus.
Schematic diagram of a terminal bouton and synapse. Labeled components include the bouton (A) surrounded by a thin basal lamina (dashed line) that extends into the narrow synaptic cleft (B), the presynaptic membrane (C), neurosecretory vesicles (D), and the postsynaptic membrane (E).
Clusters of neuron cell bodies in the PNS are called ganglia. The two major types are craniospinal ganglia and autonomic ganglia. Each ganglion contains large ganglion (neuron) cell bodies surrounded by satellite cells. Cell processes are supported by Schwann cells with smaller, elongated, pale-staining nuclei. Condensed fibroblast nuclei occur in the capsule and scattered through the ganglion. Table 9–4 compares the key structural and functional features of the two main ganglion types.
Table 9–4. Comparisons of the Two Main Types of Ganglia. ||Download (.pdf)
Table 9–4. Comparisons of the Two Main Types of Ganglia.
Examples and location
Two types: ganglia of cranial nerves in head and dorsal root (or spinal) ganglia associated with spinal cord
Two types: sympathetic ganglia lie close to the CNS in sympathetic chain, or in clusters called prevertebral ganglia and parasympathetic ganglia occur farther from CNS, often in target organs (Table 9–2); lack connective tissue capsules typical of other ganglia
Neuron type (ganglion cells)
Mainly pseudounipolar; impulses bypass cell body (Table 9–3); no synapses in these ganglia; spiral (auditory) ganglia have bipolar neurons (Table 9–3)
Large, multipolar neurons
Ganglion cell distribution
Concentrated peripherally around a core of myelinated and unmyelinated cell processes
Randomly distributed throughout ganglion
Ganglion cell nuclei
Large, spheric, and mostly central
Large, ovoid, and mostly eccentric
Relative number of satellite cells
More numerous and spheric; completely surround soma of each ganglion cell
Less numerous; discontinuous layer (interrupted by cell processes of multipolar neurons)
Peripheral nerves contain myelinated and unmyelinated axons, Schwann cells, and fibroblasts, but lack neuron cell bodies. Nuclei seen in peripheral nerve cross-sections belong to Schwann cells (large, pale-staining) or to fibrocytes (mature fibroblasts; small, dark-staining). Each peripheral nerve (Fig. 9–4) is surrounded by a dense connective tissue sheath, or epineurium, branches of which penetrate the nerve, dividing the nerve fibers into bundles, or fascicles. The sheath surrounding each fascicle is called the perineurium. Fine slips of reticular connective tissue from the perineurium penetrate the fascicles to surround each nerve fiber, forming the endoneurium. Branches of blood vessels in the epineurium penetrate the nerve along with the connective tissue. The three main fiber types in peripheral nerves (A, B, and C) are compared in Table 9–5.
Schematic diagram of a peripheral nerve in cross-section. Labeled coverings include the epineurium (A), the perineurium (B), the endoneurium (C), and the myelin sheath (D) surrounding each axon (E).
Table 9–5. Fiber Types in Peripheral Nerves. ||Download (.pdf)
Table 9–5. Fiber Types in Peripheral Nerves.
Type A Fibers
Type B Fibers
Type C Fibers
Impulse conduction velocity
VII. Histophysiology of Nerve Tissue
A. Axoplasmic (Axonal) Transport
Movement of metabolic products through the axoplasm, which can be fast (e.g., 400 mm/d) or slow (e.g., 1 mm/d), involves neurotubules and neurofilaments. Anterograde or orthograde axoplasmic transport moves newly synthesized products and synaptic vesicles toward the axon's terminal arborization and can be fast or slow. Retrograde axoplasmic transport, the return of worn materials to the perikaryon for degradation or reutilization, is usually fast.
B. Signal Generation and Transmission
The basic function of nerve tissue is to generate and transmit signals as nerve impulses, or action potentials, from one part of the body to another. The arrangement of neurons in chains and circuits allows the integration of simple on–off signals into complex information. The microscopic structure of nerve tissue (e.g., axon diameter, presence or absence of myelin) exploits physicochemical phenomena to regulate the rate and sequence of signal transmission.
Resting membrane potential. The K+ concentration is 20-fold higher inside neurons than outside, whereas the Na+ concentration is 10-fold higher outside than inside. Because the plasma membrane is more permeable to K+ than to other ions, K+ ions tend to leak out until the accumulated positive charge outside the cell inhibits further K+ movement. In this state of equilibrium, the inside of the cell is negatively charged (−40 to −100 mV) relative to the outside; this potential difference (voltage) across the membrane is the resting membrane potential. Energy-requiring pumps in the plasma membrane help maintain the resting potential, keeping the neuron ready to receive and transmit signals. The best-known pump is Na+/K+-ATPase, which exchanges internal Na+ for escaped K+ when ATP is available.
Firing and propagating action potentials. The binding of excitatory neurotransmitters (e.g., acetylcholine) to receptors in the postsynaptic membrane opens transmitter-gated ion channels (2.II.C.2.a) and allows positive ions to enter the cell, reducing the potential difference across the membrane. When this membrane depolarization reaches a critical level, or threshold, integral membrane proteins acting as voltage-gated Na+ channels open, allowing Na+ ions to rush in and reverse the membrane potential in one region of the membrane. This is the firing of the action potential. Incoming Na+ ions diffuse to nearby sites, causing threshold depolarization and opening the voltage-gated Na+ channels in these areas; thus, a wave of depolarization spreads along the neuron surface. Spread of the wave of depolarization is termed propagation of the action potential. The firing of an action potential is an “all-or-none” event and does not occur unless the threshold is reached.
Refractory period. Reversal of the membrane potential at threshold opens voltage-gated K+ channels and allows K+ ions to exit the cell, returning the membrane to its resting potential (repolarization). An even greater potential difference (hyperpolarization) may be achieved before stabilizing at normal resting levels. The refractory period is the 1- to 2-ms interval between the firing of the action potential and the restoration of the resting potential, during which another impulse cannot be generated. Na+/K+-ATPase helps restore the normal balance of ions (resting potential) across the membrane during this period.
Direction of signal transmission. For action potentials fired by neurotransmitters crossing a synapse, the sequence of depolarization is usually dendrites → soma → axon → synapse → next neuron (or end-organ). This is termed orthodromic spread. Two factors normally prevent antidromic spread along the axon toward the soma: (1) the region directly behind the newly depolarized region of the axon is refractory, and (2) the signal cannot be propagated in a reverse direction across a synapse. In response to action potentials fired artificially by electric stimulation of an axon, both orthodromic and antidromic spread occur, but the antidromic spread has no effect because it cannot cross a synapse.
Saltatory conduction. Depolarization of myelinated axons occurs only at nodes of Ranvier, where insulation is reduced and Na+ and K+ channels are concentrated. The action potential, therefore, jumps from node to node along the axons, a phenomenon called saltatory (jumping) conduction. The result is faster impulse conduction, less change in ion concentration, and thus a lower energy requirement for recovery of resting potential.
Blocking signal transmission. Cold, heat, and pressure on a nerve can block impulse conduction. Local anesthetics allow more complete and reversible impulse blocking by disturbing the resting potential. Some poisons (neurotoxins, Table 9–6) block ion channels or synaptic transmission and prevent propagation of the action potential.
Table 9–6. Examples of Neurotoxins. ||Download (.pdf)
Table 9–6. Examples of Neurotoxins.
Agitoxin, charybdotoxin, ergotoxine-1, hongotoxin, iberiotoxin, kaliotoxin, margatoxin, maurotoxin, scyllatoxin, tamapin
Brevetoxin, ciguatoxin, gonyautoxin, saxitoxin
Agatoxin, grammotoxin, huwentoxin-1, SNX-482
Calcicludine, calciseptine, taicatoxin
α- and β-bungarotoxin, cobrotoxin, erabutoxin
Black Widow Spider
Joro spider toxin
VIII. Response of Nerve Tissue to Injury
A. Damage to the Cell Body
Because mature neurons rarely divide, dead neurons cannot be readily replaced. Neurons not connected with other functioning neurons or end-organs are useless, and mechanisms have evolved to dispose of them. Thus, if a neuron makes synaptic contact with only one other neuron and the latter is destroyed, the former undergoes autolysis, a process termed transneuronal degeneration. Most neurons, however, have multiple connections.
Regeneration can occur in axons injured or severed far enough from the soma to spare the cell. Partial degeneration, and subsequent regeneration, follows.
Degeneration. A crushed or severed axon degenerates both distal and proximal to the injury. Distal to the injury, both the axon and myelin sheath degenerate completely because the connection with the soma has been lost. During this wallerian, descending, or secondary degeneration, which takes approximately 2–3 days, nearby Schwann cells proliferate, phagocytose degenerated tissue, and invade the resulting endoneurial channel. Proximal to the injury, degeneration of the axon and myelin sheath is similar but incomplete. This retrograde, ascending, or primary degeneration proceeds for approximately two internodes before the injured axon is sealed. The cell body also changes in response to injury. The perikaryon enlarges; chromatolysis, or dispersion of Nissl substance, occurs; and the nucleus moves to an eccentric position. Proximal degeneration and cell body changes take approximately 2 weeks.
Regeneration. It begins during the third week after injury. As the perikaryon gears up for increased protein synthesis, the Nissl bodies reappear. The axon's proximal stump gives off a profusion of smaller processes called neurites; one of these grows into the endoneurial channel while the others degenerate. In the channel, the neurite grows 3–4 mm/d, guided and subsequently myelinated by the Schwann cells. Growth is maintained by orthograde axoplasmic transport of material synthesized in the soma. When the neurite tip reaches its termination, it connects with its end-organ or another neuron in the chain. If a severed nerve's cut ends are matched by fascicle size and arrangement and sutured together by their epineurial sheaths within 3–4 weeks, innervation often can be restored. If the gap between the cut ends is too wide, the neurites may fail to find endoneurial sheaths and may grow out in a potentially painful disorganized swelling called a neuroma. Target organs deprived of innervation often atrophy.