Berne and Levy Physiology, 6th ed

4. The Nervous System: Introduction to Cells and Systems

 

The nervous system is a communications and control network that allows an organism to interact in appropriate ways with its environment. The environment includes both the external environment (the world outside the body) and the internal environment (the components and cavities of the body). The nervous system can be divided into central and peripheral parts, each with further subdivisions. The peripheral nervous system (PNS) provides an interface between the environment and the central nervous system (CNS). It includes sensory (or primary afferent) neurons, somatic motor neurons, and autonomic motor neurons. Autonomic motor neurons are discussed in Chapter 11.

 

The general functions of the nervous system include sensory detection, information processing, and the expression of behavior. Other systems, such as the endocrine and immune systems, share some of these functions, but the nervous system is specialized for them.

 

Sensory detection is the process whereby neurons transduce environmental energy into neural signals. Sensory detection is accomplished by special neurons called sensory receptors. Various forms of energy can be sensed, including mechanical, light, sound, chemical, thermal, and in some animals, electrical.

 

Information processing, including learning and memory, depends on intercellular communication in neural circuits. The mechanisms involve both electrical and chemical events. Information processing includes the following:

1.     Transmission of information via neural networks

2.     Transformation of information by recombination with other information (neural integration)

3.     Perception of sensory information

4.     Storage and retrieval of information (memory)

5.     Planning and implementation of motor commands

6.     Thought processes and conscious awareness

7.     Learning

8.     Emotion and motivation

 

Behavior consists of the totality of the organism's responses to its environment. Behavior may be covert, as in cognition, but animals can only overtly express behavior with a motor act (such as a muscle contraction) or an autonomic response (such as glandular release). In humans, language constitutes a particularly important set of behaviors, and plays a role in the processing and storage of information. Learning and memory are special forms of information processing that permit behavior to change appropriately in response to previously experienced environmental challenges.

 

CELLULAR COMPONENTS OF THE NERVOUS SYSTEM

 

The nervous system is made up of cells, connective tissue, and blood vessels. The major cell types are neurons (nerve cells) and neuroglia ("nerve glue"). Neurons are anatomically and physiologically specialized for communication and signaling, and these properties are fundamental to function of the nervous system. Traditionally, neuroglia, or just glia, are characterized as supportive cells that sustain neurons both metabolically and physically, as well as isolate individual neurons from each other and help maintain the internal milieu of the nervous system.

 

Neurons

 

The functional unit of the nervous system is the neuron (Fig. 4-1), and neural circuits are made up of synaptically interconnected neurons. Neural activity is generally coded by sequences of action potentials propagated along axons in the neural circuits (see Chapter 5). The coded information is passed from one neuron to the next by synaptic transmission (see Chapter 6). In synaptic transmission, the action potentials that reach a presynaptic ending usually trigger the release of a chemical neurotransmitter. The neurotransmitter can either excite the postsynaptic cell (possibly to discharge one or more action potentials), inhibit the activity of the postsynaptic cell, or influence the action of other axon terminals.

 

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Figure 4-1 Schematic diagram of an idealized neuron and its major components. Most afferent input from axons of other cells terminates in synapses on the dendrites (d), although some may terminate on the soma (S). Excitatory terminals tend to terminate more distally on dendrites than inhibitory ones do, which often terminate on the soma. (Redrawn from Williams PL, Warwick R: Functional Neuroanatomy of Man. Edinburgh, Churchill Livingstone, 1975.)

 

The typical neuron consists of a cell body, or soma, and a variable number of branch-like dendrites and another that extends from the soma, the axon. The cell body (perikaryon, soma) of the neuron contains the nucleus and nucleolus of the cell and also possesses a well-developed biosynthetic apparatus for manufacturing membrane constituents, synthetic enzymes, and other chemical substances needed for the specialized functions of nerve cells. The neuronal biosynthetic apparatus includes Nissl bodies, which are stacks of rough endoplasmic reticulum, and a prominent Golgi apparatus. The soma also contains numerous mitochondria and cytoskeletal elements, including neurofilaments and microtubules. In contrast to most cells in the body, neurons have an enormous variety of shapes and sizes. Neurons with similar morphologies often characterize specific regions of the CNS. Morphological variation is produced by differences in the branching pattern of dendrites and the axon.

 

Dendrites are tapering and branching extensions of the soma and generally convey information toward the cell body. A neuron's branched set of dendrites is termed its dendritic tree. In some neurons the dendrites are longer than 1 mm, and they may account for more than 90% of the surface area. The proximal dendrites (near the cell body) contain Nissl bodies and parts of the Golgi apparatus. However, the main cytoplasmic organelles in dendrites are microtubules and neurofilaments. Because the dendrites are the major area that receives synaptic input from other neurons, the shape and size of the dendritic tree, as well as the population and distribution of channels in the dendritic membrane, are important determinants of how the synaptic input will affect the neuron. Synaptic input to dendrites can be passively conducted to the cell body, but these signals usually diminish as they pass to the soma and, in large cells, would have little influence on it. However, the dendrites of large neurons may have active zones, often using Ca++-dependent, voltage-dependent channels, that can produce voltage spikes important in the integration of multiple synaptic input to a single neuron (see Chapter 6).

 

The axon is an extension of the cell that conveys the output of the cell to the next neuron or, in the case of a motor neuron, to a muscle. In general, each neuron has only one axon, and it is usually of uniform diameter. The length and diameter of axons vary with the neuronal type. Some axons do not extend much beyond the length of the dendrites, whereas others may be a meter or more long. Axons may have orthogonal branches en passant, but they often end in a spray of branches called terminal arborization (Fig. 4-1). The size, shape, and organization of the terminal arborization determine which other cells it will contact. The axon arises from the soma (or sometimes from a proximal dendrite) in a specialized region called the axon hillock. The axon hillock and axon differ from the soma and proximal dendrites in that they lack rough endoplasmic reticulum, free ribosomes, and Golgi apparatus. The axon hillock is usually the site where action potentials are generated because it has a high concentration of the necessary channels (see Chapters 5 and 6). Because the soma is the metabolic engine for the axon, it is only reasonable that a large soma is required to support large, long axons and that very small neurons are associated with short axons. Thus, axons not only transmit information in neural circuits but also convey chemical substances toward or away from the synaptic terminals by axonal transport. For this reason also, axons degenerate when disconnected from the cell body.

 

Axonal Transport

 

Most axons are too long to allow efficient movement of substances from the soma to the synaptic endings by simple diffusion. Membrane and cytoplasmic components that originate in the biosynthetic apparatus of the soma must be distributed to replenish secreted or inactivated materials along the axon and, especially, to the presynaptic elements at the terminal end. A special transport mechanism called axonal transport accomplishes this distribution (Fig. 4-2).

 

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Figure 4-2 Axonal transport has been proposed to depend on the movement of transport filaments. Energy is required and is supplied by glucose. Mitochondria control the level of cations in the axoplasm by supplying ATP to the ion pumps. An important cation for axonal transport is Ca++. Transport filaments move along the cytoskeleton (microtubules [M] or neurofilaments [NF]) by means of cross-bridges. Transported components attach to the transport filaments. CaBP, Ca++-binding protein; NF, neurofilaments.

 

Several types of axonal transport exist. Membrane-bound organelles and mitochondria are transported relatively rapidly by fast axonal transport. Substances that are dissolved in cytoplasm, such as proteins, are moved by slow axonal transport. In mammals, fast axonal transport proceeds as rapidly as 400 mm/day, whereas slow axonal transport occurs at about 1 mm/day. Synaptic vesicles, which travel by fast axonal transport, can travel from the soma of a motor neuron in the spinal cord to a neuromuscular junction in a person's foot in about 2.5 days. In comparison, the movement of some soluble proteins over the same distance can take nearly 3 years.

 

Axonal transport requires metabolic energy and involves calcium ions. Microtubules provide a system of guide wires along which membrane-bound organelles move (Fig. 4-2). Organelles attach to microtubules through a linkage similar to that between the thick and thin filaments of skeletal muscle fibers. Ca++ triggers movement of the organelles along the microtubules. Special microtubule-associated motor proteins called kinesin and dynein are required for axonal transport.

 

Axonal transport occurs in both directions. Transport from the soma toward the axonal terminals is called anterograde axonal transport. This process involves kinesin, and it allows the replenishment of synaptic vesicles and enzymes responsible for the synthesis of neurotransmitters in synaptic terminals. Transport in the opposite direction, which is driven by dynein, is called retrograde axonal transport. This process returns recycled synaptic vesicle membrane to the soma for lysosomal degradation.

 

THE SUPPORTIVE MATRIX OF THE CENTRAL NERVOUS SYSTEM

 

The local environment of most CNS neurons is controlled such that neurons are normally protected from extreme variations in the composition of the extracellular fluid that bathes them. This control is provided by the buffering functions of neuroglia, regulation of the CNS circulation, the presence of a blood-brain barrier, and exchange of substances between the cerebrospinal fluid (CSF) and extracellular fluid of the CNS.

 

Neuroglia

 

IN THE CLINIC

 

Certain viruses and toxins can be conveyed by axonal transport along peripheral nerves. For example, herpes zoster, the virus of chickenpox, invades dorsal root ganglion cells. The virus may be harbored by these neurons for many years. However, eventually, the virus may become active because of a change in immune status. The virus may then be transported along the sensory axons to the skin. Another example is the axonal transport of tetanus toxin. Clostridium tetani bacteria may grow in a dirty wound, and if the person had not been vaccinated against tetanus toxin, the toxin can be transported retrogradely in the axons of motor neurons. The toxin can escape into the extracellular space of the spinal cord ventral horn and block the synaptic receptors for inhibitory amino acids. This process can result in tetanic convulsions.

 

 

The major nonneuronal cellular elements of the nervous system are the neuroglia (Fig. 4-3), or supportive cells. Neuroglial cells in the human CNS outnumber neurons by an order of magnitude: there are about 1013 neuroglia and 1012 neurons.

 

Neuroglia do not participate directly in the short-term communication of information through the nervous system, but they do assist in that function. For example, some types of neuroglial cells take up neurotransmitter molecules and in this manner directly influence synaptic activity. Others provide many axons with myelin sheaths that speed up the conduction of action potentials along axons (see Chapter 5) and thereby allow some axons to communicate rapidly over relatively long distances.

 

Neuroglial cells in the CNS include astrocytes and oligodendroglia (Fig. 4-3) and, in the PNS, Schwann cells and satellite cells. Microglia and ependymal cells are also considered to be central neuroglial cells.

 

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Figure 4-3 Schematic representation of nonneural elements in the CNS. Two astrocytes are shown ending on a neuron's soma and dendrites. They also contact the pial surface or capillaries, or both. An oligodendrocyte provides the myelin sheaths for axons. Also shown are microglia and ependymal cells. (Redrawn from Williams PL, Warwick R: Functional Neuroanatomy of Man. Edinburgh, Churchill Livingstone, 1975.)

 

Astrocytes (named for their star shape) help regulate the microenvironment of the CNS. Their processes contact neurons and surround groups of synaptic endings, isolating them from adjacent synapses and the general extracellular space. Astrocytes also have foot processes that contact the capillaries and connective tissue at the surface of the CNS, the pia mater (Fig. 4-3). These foot processes may help mediate the entry of substances into the CNS. Astrocytes can actively take up K+ ions and neurotransmitter substances, which they metabolize, biodegrade, or recycle. Thus, astrocytes serve to buffer the extracellular environment of neurons with respect to both ions and neurotransmitters. The cytoplasm of astrocytes contains glial filaments, which provide mechanical support for CNS tissue. After injury, the astrocytic processes that contain these glial filaments hypertrophy and form a glial "scar."

 

AT THE CELLULAR LEVEL

 

Astrocytes are coupled to each other by gap junctions such that they form a syncytium through which small molecules and ions can redistribute along their concentration gradients or by current flow. When normal neural activity gives rise to a local increase in extracellular [K+], this coupled network can enable the spatial redistribution of K+ over a wide area via current flow in many astrocytes.

 

Under conditions of hypoxia, such as might be associated with ischemia secondary to blockage of an artery (i.e., a stroke), [K+] in the extracellular space of a brain region can increase by a factor of as much as 20. This will depolarize neurons and synaptic terminals and result in the release of transmitters such as glutamate, which will cause further release of K+ from neurons. The additional release only exacerbates the problem and can lead to neuronal death. Under such conditions, local astroglia will probably take up the excess K+ by K+-Cl- symport rather than by spatial buffering because the elevation in extracellular [K+] tends to be widespread rather than local.

 

 

Many axons are surrounded by a myelin sheath, which is a spiral multilayered wrapping of glial cell membrane (Fig. 4-4, also see Fig. 4-1). In the CNS, myelinated axons are ensheathed by the membranes of oligodendroglia (Fig. 4-4, A), and unmyelinated axons are bare. In the PNS, unmyelinated axons are surrounded by Schwann cells (Fig. 4-4, C), whereas myelinated axons are ensheathed by multiply wrapped membranes of Schwann cells, much as the oligodendroglia ensheath central axons. One major distinction is that many central axons can be myelinated by a single oligodendroglial cell, whereas in the periphery, each Schwann cell ensheathes only one axon. Myelin increases the speed of action potential conduction, in part by restricting the flow of ionic current to small unmyelinated portions of the axon between adjacent sheath cells, the nodes of Ranvier (Fig. 4-4, B; see also Chapter 5).

 

Satellite cells encapsulate dorsal root and cranial nerve ganglion cells and regulate their microenvironment in a fashion similar to that used by astrocytes.

 

Microglia are latent phagocytes. When the CNS is damaged, microglia help remove the cellular products of the damage. They are assisted by neuroglia and by other phagocytes that invade the CNS from the circulation.

 

Ependymal cells form the epithelium lining the ventricular spaces of the brain that contain CSF. Many substances diffuse readily across the ependyma, which lies between the extracellular space of the brain and the CSF. CSF is secreted in large part by specialized ependymal cells of the choroid plexuses located in the ventricular system.

 

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Figure 4-4 Myelin sheaths of axons. A, Myelinated axons in the CNS. A single oligodendrocyte (G) emits several processes, each of which winds in a spiral fashion around an axon to form the myelin sheath. The axon is shown in cutaway. The myelin from a single oligodendrocyte ends before the next wrapping from another oligodendrocyte. The bare axon between segments is the node of Ranvier (N). Conduction of action potentials is saltatory down the axon, skipping from node to node. B, Myelinated axon in the PNS shown in a longitudinal view. The node of Ranvier (N) is shown between adjacent sheaths formed by two Schwann cells (S1 and S2). (Redrawn from Patton HD et al: Introduction to Basic Neurology. Philadelphia, Saunders, 1976.) C, Three-dimensional impression of the appearance of a bundle of unmyelinated axons enwrapped by Schwann cells. The cut face of the bundle is seen to the left. One of the three unmyelinated axons is represented as protruding from the bundle. A mesaxon is indicated, as is the nucleus of the Schwann cell. To the right, the junction with an adjacent Schwann cell is depicted.

 

Most neurons in the adult nervous system are postmitotic cells (although some stem cells may also remain in certain sites in the brain). Many glial precursor cells are present in the adult brain, and they can still divide and differentiate. Thus, the cellular elements that give rise to most intrinsic brain tumors in the adult brain are the glial cells. For example, brain tumors can be derived from astrocytes (which vary in malignancy from the slowly growing astrocytoma to the rapidly fatal glioblastoma multiforme), from oligodendroglia (oligodendroglioma), or from ependymal cells (ependymoma). Meningeal cells can also give rise to slowly growing tumors (meningiomas) that compress brain tissue, as Schwann cells do (e.g., "acoustic neurinomas," which are tumors formed by Schwann cells of the eighth cranial nerve). In the brain of infants, neurons that are still dividing can sometimes give rise to neuroblastomas (e.g., of the roof of the fourth ventricle) or retinoblastomas (in the eye).

 

The Blood-Brain Barrier

 

Movement of large molecules and highly charged ions from blood into the brain and spinal cord is severely restricted. The restriction is at least partly due to the barrier action of the capillary endothelial cells of the CNS and the tight junctions between them. Astrocytes may also help limit the movement of certain substances. For example, astrocytes can take up potassium ions and thus regulate [K+] in the extracellular space. Some pharmaceutical agents, such as penicillin, are removed from the CNS by transport mechanisms.

 

THE CENTRAL NERVOUS SYSTEM

 

The CNS, among other functions, gathers information about the environment from the PNS; processes this information and perceives part of it; organizes reflex and other behavioral responses; is responsible for cognition, learning, and memory; and plans and executes voluntary movements. The CNS includes the spinal cord and the brain (Fig. 4-5).

 

IN THE CLINIC

 

The blood-brain barrier can be disrupted by pathology of the brain. For example, brain tumors may allow substances that are otherwise excluded to enter the brain from the circulation. Radiologists can exploit this by introducing a substance into the circulation that normally cannot penetrate the blood-brain barrier. If the substance can be imaged, its leakage into the region occupied by the brain tumor can be used to demonstrate the distribution of the tumor.

 

 

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Figure 4-5 Schematic of the major components of the CNS as shown in a longitudinal midline view. (From Haines DE [ed]: Fundamental Neuroscience for Basic and Clinical Applications, 3rd ed. Philadelphia, Churchill Livingstone, 2006.)

 

 

 

Figure 4-6 Lateral view of the human brain showing the left cerebral hemisphere, cerebellum, pons, and medulla. Note the division of the lobes of the cerebrum (frontal, parietal, occipital, and temporal) and the two major fissures (lateral and central). (From Nolte J, Angevine J: The Human Brain in Photographs and Diagrams, 2nd ed. St Louis, Mosby, 2000.)

 

All vertebrate nervous systems begin as an invagination of a longitudinal groove in a thickened ectodermal plate, the neural plate. Closure of the neural groove results in the formation of a hollow neural tube that is bordered dorsolaterally by columns of neural crest. The ectoderm closes over the invaginated neural tube to form the skin of the back. The neural tube subsequently develops into the CNS, whereas the neural crest is the source of cells in the dorsal root and autonomic ganglia, Schwann cells, Merkel's disks, and melanocytes, to name a few.

 

The upper part of the neural tube dilates into three primary brain vesicles, the rhombencephalon, mesencephalon, and prosencephalon. The rhombencephalic vesicle (rhombencephalon = rhomboid- or diamond-shaped brain) is continuous with the spinal cord caudally. The rhombencephalon develops into a caudal portion, the medulla oblongata, and a rostral portion that includes the pons and cerebellum. The mesencephalon becomes the midbrain. Above the prosencephalon develops into the diencephalon (thalamus and hypothalamus), and the telencephalon (cerebrum) most rostrally. The spaces in these vesicles become the fluid-filled ventricles and cerebral aqueduct. The largest, the lateral ventricles, develop inside the telencephalon; the narrow third ventricle remains between the two halves of the diencephalon. The narrow lumen of the mesencephalon becomes the cerebral aqueduct, and the fourth ventricle is the space of the rhombencephalon.

 

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Figure 4-7 Representative sections through the brain at various levels, with the major landmarks labeled. A, Cerebrum and thalamus; B, midbrain; C, upper pons; D, lower pons; E, upper medulla; F, lower medulla; G, junction of the medulla and spinal cord; H, cervical spinal cord.

 

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The enormous expansion of the telencephalon eventually covers the thalamus, midbrain, and portions of the cerebellum. The expanding telencephalon takes on a shape not unlike a boxing glove. The surface area of the telencephalon is divided into five deeply furrowed lobes named after the overlying bones of the skull: the frontal, parietal, temporal, and occipital lobes (Fig. 4-6). The right and left cerebral hemispheres are connected across the midline by a massive bundle of axons, the corpus callosum (Fig. 4-7, A). Expansion of the frontal, parietal, and temporal lobes buries and isolates the insula, hence its name, deep within the lateral fissure (Fig. 4-7A).

 

The spinal cord (lower part of Fig. 4-5) can be subdivided into a series of regions, each composed of a number of segments named for the vertebrae where their nerve roots enter or leave: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. Each portion maintains its tubular appearance, although its lumen, the spinal canal, may not remain patent (Fig. 4-7, H).

 

The major functions of the different parts of the CNS are listed in Table 4-1.

 

Cellular Circuitry in the Central Nervous System

 

Sensory receptors can be classified in terms of the type of energy that they transduce (e.g., photoreceptors transduce light, mechanoreceptors transduce displacement and force) or according to the source of the input (e.g., exteroceptors signal external events, proprioceptors signal the position of a body part with respect to space or another body part). Primary afferent neurons are connected peripherally to sensory receptors, which are specialized structures that transduce changes in environmental energy. In general, that information is transmitted to the CNS by trains of action potentials in primary afferent neurons. The cell bodies of primary afferent neurons are located in dorsal root and cranial nerve ganglia. Each primary afferent neuron has two types of processes: (1) a peripheral process that extends distally within a peripheral nerve to reach the appropriate sensory receptors and (2) a central process that enters the CNS through a dorsal root or a cranial nerve (Fig. 4-8).

 

In the CNS, axons often travel in bundles or tracts. The names applied to tracts usually describe their origin and termination. For example, the spinocerebellar tract conveys information from the spinal cord to the cerebellum. The term pathway is similar to tract but is generally used to suggest a particular function (e.g., the auditory pathway: a series of neuron-to-neuron links, across several synapses, that convey and process auditory information).

 

 

 

Table 4-1. Parts and Functions of the Central Nervous System

 

Region

Nerves (Input/Output)

General Functions

Spinal cord

Dorsal/ventral roots

Sensory input, reflex circuits, somatic and autonomic motor output

Medulla

Cranial nerves VIII-XII

Cardiovascular and respiratory control, auditory and vestibular input, brainstem reflexes

Pons

Cranial nerves V-VIII

Respiratory/urinary control, control of eye movement, facial sensation/motor control

Cerebellum

Cranial nerve VIII

Motor coordination, motor learning, equilibrium

Midbrain

Cranial nerves III-IV

Acoustic relay and mapping, control of the eye (including movement, lens and pupillary reflexes), pain modulation

Thalamus

Cranial nerve II

Sensory and motor relay to the cerebral cortex, regulation of cortical activation, visual input

Hypothalamus

 

Autonomic and endocrine control, motivated behavior

Basal ganglia

 

Shape patterns of thalamocortical motor inhibition

Cerebral cortex

Cranial nerve I

Sensory perception, cognition, learning and memory, motor planning and voluntary movement, language

 

 

 

Behavior is expressed by movement brought about through the contraction of muscle fibers or by the release of chemical compounds from glands. These events are triggered by the activation of motor neurons, the term applied to cells whose axons leave the CNS to affect the periphery. For example, a motor unit can be regarded as the basic unit of movement, and it consists of an α motor neuron, its axon, and all the skeletal muscle fibers that it supplies. A given α motor neuron (and its motor unit) may participate in a variety of reflexes and in voluntary movement as it responds to the central neurons and pathways that synapse on it. Because the α motor neuron (in mammals) and its axon represent the only means of communication between the nervous system and the muscle, these motor neurons have been termed the final common pathway. They are also sometimes referred to as "lower motor neurons" to distinguish them from the central "upper motor neurons," which synapse on them via various central pathways.

 

 

 

Figure 4-8 Diagram of the spinal cord, spinal roots, and spinal nerve. A primary afferent neuron is shown with its cell body in the dorsal root ganglion and its central and peripheral processes distributed, respectively, to the spinal cord gray matter and to a sensory receptor in the skin. An α motor neuron is shown to have its cell body in the spinal cord gray matter and to project its axon out the ventral root to innervate a skeletal muscle fiber.

 

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Regions of the CNS containing high concentrations of axon pathways (and very few neurons) are called white matter because the axonal myelin sheaths of the axons are highly refractive to light. Regions containing high concentrations of neurons and dendrites are, by contrast, called gray matter. Axons are also present in gray matter. Gray matter has a much higher metabolic rate than white matter does and consequently is more highly vascularized. A group of neurons in the CNS is called a nucleus, similar to what would be called a ganglion outside the CNS. When neurons are organized into layers, they may form a cortex. The most prominent cortex covers the entire surface of the cerebral hemispheres, where its structural variation reflects the general functional organization of the cerebrum (see Fig. 10-3).

 

Cerebrospinal Fluid

 

CSF fills the ventricular system, a series of interconnected spaces within the brain, and the subarachnoid space directly surrounding the brain. The volume of CSF within the cerebral ventricles is approximately 30 mL, and that in the subarachnoid space is about 125 mL. Because about 0.35 mL of CSF is produced each minute, CSF is turned over more than three times daily. The intraventricular CSF reflects the composition of the brain's extracellular space via free exchange across the ependyma, and the brain "floats" in the subarachnoid CSF to minimize the effect of external mechanical forces.

 

CSF is formed largely by the choroid plexuses, which contain ependymal cells specialized for transport. The choroid plexuses are located in the lateral, third, and fourth ventricles (Fig. 4-9). The lateral ventricles are situated within the two cerebral hemispheres. They connect with the third ventricle through the interventricular foramina (of Monro). The third ventricle lies in the midline between the diencephalon on the two sides. The cerebral aqueduct (of Sylvius) traverses the midbrain and connects the third ventricle with the fourth ventricle. The fourth ventricle is interposed between the pons and medulla below and the cerebellum above. The central canal of the spinal cord continues caudally from the fourth ventricle, although in adult humans the canal is not generally patent.

 

 

 

Figure 4-9 Midsagittal view of the brain showing the third and fourth ventricles, the cerebral aqueduct of the midbrain, and the choroid plexus. The CSF formed by the choroid plexus in the lateral ventricles enters this circulation via the interventricular foramen. Note also the location of the corpus callosum and other commissures. (From Haines DE [ed]: Fundamental Neuroscience for Basic and Clinical Applications, 3rd ed. Philadelphia, Churchill Livingstone, 2006.)

 

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CSF escapes from the ventricular system through three apertures (the medial aperture of Magendie and the two lateral apertures of Luschka) located in the roof of the fourth ventricle. After it leaves the ventricular system, CSF circulates through the subarachnoid space that surrounds the brain and spinal cord. Regions where these spaces are expanded are called subarachnoid cisterns. An example is the lumbar cistern, which surrounds the lumbar and sacral spinal roots below the level of termination of the spinal cord. The lumbar cistern is the target for lumbar puncture, a procedure used clinically to sample CSF. A large part of CSF is removed by bulk flow through the valvular arachnoid granulations into the dural venous sinuses in the cranium.

 

 

 

Table 4-2. Constituents of Cerebrospinal Fluid and Blood

 

Constituent

Lumbar CSF

Blood

Na+ (mEq/L)

148

136-145

K+ (mEq/L)

2.9

3.5-5

Cl- (mEq/L)

120-130

100-106

Glucose (mg/dL)

50-75

70-100

Protein (mg/dL)

15-45

6.8 × 103

pH

7.3

7.4

 

 

From Willis WD, Grossman RG: Medical Neurobiology, 3rd ed. St Louis, Mosby, 1981.

 

Because the extracellular fluid within the CNS communicates with the CSF, the composition of the CSF is a useful indicator of the composition of the extracellular environment of neurons in the brain and spinal cord. The main constituents of CSF in the lumbar cistern are listed in Table 4-2. For comparison, the concentrations of the same constituents in blood are also given. CSF has a lower concentration of K+, glucose, and protein but a greater concentration of Na+ and Cl- than blood does. Furthermore, CSF contains practically no blood cells. The increased concentration of Na+ and Cl- enables CSF to be isotonic to blood despite the much lower concentration of protein in CSF.

 

The pressure in the CSF column is about 120 to 180 mm H2O when a person is recumbent. The rate at which CSF is formed is relatively independent of the pressure in the ventricles and subarachnoid space, as well as systemic blood pressure. However, the absorption rate of CSF is a direct function of CSF pressure.

 

NERVOUS TISSUE REACTIONS TO INJURY

 

Injury to nervous tissue elicits responses by neurons and neuroglia. Severe injury causes cell death. Except in specific instances, once a neuron is lost, it cannot be replaced because neurons are postmitotic cells.

 

Degeneration

 

 

 

Figure 4-10 A, Normal motor neuron innervating a skeletal muscle fiber. B, A motor axon has been severed, and the motor neuron is undergoing chromatolysis. C, This is associated in time with sprouting and, in D, with regeneration of the axon. The excess sprouts degenerate. E, When the target cell is reinnervated, chromatolysis is no longer present.

 

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IN THE CLINIC

 

Obstruction of the circulation of CSF leads to increased CSF pressure and hydrocephalus, an abnormal accumulation of fluid in the cranium. In hydrocephalus the ventricles become distended, and if the increase in pressure is sustained, brain substance is lost. When the obstruction is within the ventricular system or in the foramina of the fourth ventricle, the condition is called a noncommunicating hydrocephalus. If the obstruction is in the subarachnoid space or the arachnoid villi, it is known as a communicating hydrocephalus.

 

 

When an axon is transected, the soma of the neuron may show an "axonal reaction," or chromatolysis. Normally, Nissl bodies stain well with basic aniline dyes, which attach to the RNA of ribosomes (Fig. 4-10, A). After injury to the axon (Fig. 4-10, B), the neuron attempts to repair the axon by making new structural proteins, and the cisterns of the rough endoplasmic reticulum become distended with the products of protein synthesis. The ribosomes appear to be disorganized, and the Nissl bodies are stained weakly by basic aniline dyes. This process, called chromatolysis, alters the staining pattern (Fig. 4-10, C). In addition, the soma may swell and become rounded, and the nucleus may assume an eccentric position. These morphological changes reflect the cytological processes that accompany increased protein synthesis.

 

Because it cannot synthesize new protein, the axon distal to the transection dies (Fig. 4-10, C). Within a few days, the axon and all the associated synaptic endings disintegrate. If the axon had been a myelinated axon in the CNS, the myelin sheath would also fragment and eventually be removed by phagocytosis. However, in the PNS the Schwann cells that had formed the myelin sheath remain viable, and in fact they undergo cell division. This sequence of events was originally described by Waller and is called wallerian degeneration.

 

If the axons that provide the sole or predominant synaptic input to a neuron or to an effector cell are interrupted, the postsynaptic cell may undergo transneuronal degeneration and even death. The best known example of this is atrophy of skeletal muscle fibers after their innervation by motor neurons has been interrupted. If only one or a few axons are removed, the other surviving axons may sprout additional terminals, thereby taking up the synaptic space of the damaged axons and increasing their influence on the postsynaptic cell.

 

Regeneration

 

In the PNS, after an axon is lost through injury, many neurons can regenerate a new axon. The proximal stump of the damaged axon develops sprouts (Fig. 4-10, C), these sprouts elongate, and they grow along the path of the original nerve if this route is available (Fig. 4-10, D). The Schwann cells in the distal stump of the nerve not only survive the wallerian degeneration but also proliferate and form rows along the course previously taken by the axons. Growth cones of the sprouting axons find their way along these rows of Schwann cells, and they may eventually reinnervate the original peripheral target structures (Fig. 4-10, E). The Schwann cells then remyelinate the axons. The rate of regeneration is limited by the rate of slow axonal transport to about 1 mm/day.

 

In the CNS, transected axons also sprout. However, proper guidance for the sprouts is lacking, in part because the oligodendroglia do not form a path along which the sprouts can grow. This limitation may be a consequence of the fact that a single oligodendroglial cell myelinates many central axons, whereas a single Schwann cell provides myelin for only a single axon in the periphery. In addition, different chemical signals may affect peripheral and central attempts at regeneration differently. Another obstacle to CNS regeneration is the formation of a glial scar by astrocytes.

 

Trophic Factors

 

A number of proteins are now known to affect the growth of axons and maintenance of synaptic connections. The best studied of these substances is nerve growth factor (NGF). NGF was initially thought to enhance the growth and maintain the integrity of many neurons of neural crest origin, including small dorsal root ganglion cells and autonomic postganglionic neurons. However, NGF also affects some neurons in the CNS.

 

Many other growth factors have also been described, including the brain-derived growth factors neurotrophin 3, neurotrophin 4, neurotrophin 5, and ciliary neurotrophic factor. Some of these factors affect the growth of large dorsal root ganglion cells or motor neurons.

 

A large assortment of molecular factors play roles in the differentiation, growth, and migration of neurons to their proper locations in the PNS and CNS, and another large contingent influences the growth and guidance of axons as they extend from neurons to reach their proper synaptic targets. Prenatal and perinatal disruption of these factors secondary to genetic or environmental influences can result in malformations, ectopic locations, and errors in circuitry that can be associated with functional deficits from the punctate (e.g., loss of a single function) to the global (e.g., mental retardation). Known environmental influences include radiation, chemical exposure, maternal alcohol consumption, and malnutrition.

 

KEY CONCEPTS

 

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1.     General functions of the nervous system include excitability, sensory detection, information processing, and behavior. Different types of neurons are specialized for different functions.

2.     The CNS includes the spinal cord and brain. The brain includes the medulla, pons, cerebellum, midbrain, thalamus, hypothalamus, basal ganglia, and cerebral cortex.

3.     The PNS includes primary afferent neurons and the sensory receptors that they innervate, somatic motor neurons, and autonomic neurons.

4.     The neuron is the functional unit of the nervous system. Neurons contain a nucleus and nucleolus, Nissl bodies (rough endoplasmic reticulum), Golgi apparatus, mitochondria, neurofilaments, and microtubules.

5.     Information is conveyed through neural circuits by action potentials in the axons of neurons and by synaptic transmission between axons and the dendrites and somas of other neurons or between axons and effector cells.

6.     Sensory receptors include exteroceptors, interoceptors, and proprioceptors. Stimuli are environmental events that excite sensory receptors, responses are the effects of stimuli, and sensory transduction is the process by which stimuli are detected.

7.     Sensory receptors can be classified in terms of the type of energy they transduce or according to the source of the input. Central pathways are usually named by their origin and termination or for the type of information conveyed. The motor neuron is the only means of communication between the CNS and effectors, like muscles and glands. It is often referred to as "the final common pathway" as it is the only way for the CNS to express its operations as behavior.

8.     Chemical substances are distributed along the axons by fast or by slow axonal transport; the direction of axonal transport may be anterograde or retrograde.

9.     Neuroglial cells include astrocytes (regulate the CNS microenvironment), oligodendroglia (form CNS myelin), Schwann cells (form PNS myelin), ependymal cells (line the ventricles), and microglia (CNS macrophages). Myelin sheaths increase the conduction velocity of axons.

10. Choroid plexuses form CSF. CSF differs from blood in having a lower concentration of K+, glucose, and protein and a higher concentration of Na+ and Cl-; CSF normally lacks blood cells.

11. The extracellular fluid composition of the CNS is regulated by CSF, the blood-brain barrier, and astrocytes.

12. Damage to the axon of a neuron causes an axonal reaction (chromatolysis) in the cell body and wallerian degeneration of the axon distal to the injury. Regeneration of PNS axons is more likely than regeneration of CNS axons.

13. The growth and maintenance of axons are affected by trophic factors such as nerve growth factor.



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