Section 17: Central Nervous System

Ronald A. Bergman, Ph.D., Adel K. Afifi, M.D., Paul M. Heidger, Jr., Ph.D.
Peer Review Status: Externally Peer Reviewed

Plates

Knowledge of the structural organization of the nervous system is essential to the proper understanding of its normal, as well as altered, function.

For didactic purposes, the nervous system is generally divided into central and peripheral components. The central nervous system includes the brain and the spinal cord. The peripheral nervous system includes cranial and peripheral nerves and associated ganglia. The autonomic nervous system includes parts of the central and peripheral nervous systems.

The brain includes the cerebral hemispheres, the cerebellum, and the brain stem. The latter includes the diencephalon; mesencephalon, or midbrain; pons; and medulla oblongata. Each of these components is made up of cell groups and fibers, arranged in a manner that characterizes the particular component. Bundles of nerve fibers serving a common function and sharing a common origin and destination are grouped together in tracts or fasciculi. A group of neurons serving a common function forms a nucleus.

Knowledge of the existence and location of tracts has been gained through years of clinical observation and experimentation in both animals and man. Some of the methods used in the tracing of neural pathways follow:

1. Study of normal preparations: Many aspects of fiber connectivity of the nervous system have been elucidated by early studies using normal material and methods that demonstrate myelin sheaths (Weigert and Weil methods) or that impregnate cell bodies and their processes (Golgi method). The disadvantage of these methods is the difficulty of determining the site of termination of these fibers.
   
2. Myelinogenesis: This method, introduced by Flechsig, makes use of the fact that different fiber tracts become myelinated at different times in their development. Thus, study of the nervous system in embryos and in early neonatal life often affords information about the existence and locality of the different fiber tracts. This method is infrequently used today.
   
3. Study of pathological conditions in man and experimental lesions in animals: This method accounts for most of our current knowledge of neural connectivity. Although human material has been of use, experimentally produced lesions in animals have the major advantage of selectivity of site and size. Caution should be exercised, however, in applying to humans results achieved in experimental animals.
   
   After a lesion has been produced in animals or man and sufficient time has elapsed for anterograde degeneration to set in, the brains and spinal cords can be studied, and degenerated tracts can be localized by one of the following three methods:
   1. Methods that stain normal myelin (Weigert, Weil): In such preparations, normal myelin appears dark blue or black, and the degenerated tracts will be conspicuous by their failure to pick up the stain.
   2. Methods that stain degenerating myelin (Marchi): In such preparations, only degenerating myelinated tracts pick up the stain and can be followed from origin to termination. Normal myelinated tracts remain unstained. A major advantage of the Marchi method is that positive results may be obtained years after degeneration has occurred, making it particularly useful in the study of human material postmortem. One disadvantage of this method is that thinly myelinated or unmyelinated tracts will not stain. Another disadvantage is that it does not stain degenerating terminals; hence, the exact site of termination of a tract cannot be determined with certainty.
   3. Methods that stain degenerating axons (Nauta-Gygax, Fink-Heimer, De Olmos): These are silver impregnation techniques that stain degenerating axons and pre-terminals (Nauta-Gygax) or terminals (Fink-Heimer, De Olmos). These methods have a distinct advantage over myelin methods, since they are capable of revealing poorly myelinated as well as unmyelinated nerve fibers, because the axon, and not the myelin, is stained by these methods.
      
      A neuroanatomist is interested not only in the location and course of fiber tracts but also in their site of termination. To determine the latter, methods that stain the terminal boutons (Glees, Bodian) are used. Electron microscopy can also be used for this purpose.
      
4. Retrograde cell changes: By this method, the position of neurons giving rise to the tract is determined. Such neurons undergo chromatolytic changes of their Nissl substance or disappear completely (retrograde degeneration) if their axon is severed. These changes can be demonstrated by any of the methods that stain ribonucleic acids (Nissl material), the Nissl stains.
   
5. Autoradiography: This is a relatively recent pathway tracing technique used in brain research. it utilizes the principle that radioactive amino acids injected in the vicinity of neuronal perikarya will be taken up by the neuron, incorporated into its macromolecules, and transported anterograde along the axon to its terminal. After a finite time following injection, the radioactive amino acid can be demonstrated by autoradiography. By this method, the path of a neural tract can be traced from its origin to its termination.
   
6. Enzymatic method: When the enzyme horseradish peroxidase (HRP) is injected at the site of termination of nerve fibers, it is taken up by the nerve terminals and transported retrograde to the perikaryon where it is visualized by an enzyme histochernical technique as brown granules in the soma and dendrites.
   
7. Fluorescence method: This method, introduced in the early 1960s, is used to trace the fiber pathways of adrenergic and monaminergic neural systems. It relies on the observation that primary amines form fluorescent condensation products when treated with formaldehyde in the presence of protein. Fluorescent condensation products are demonstrated in cells, axons, and terminals by fluorescence microscopy.
   
8. Physiological exploration: By this method, stimulation and recording techniques are used to establish the presence or absence of structural and/or functional relationships between two or more loci in the nervous system. The stimulation and recording of evoked potentials may be orthodromic (recording of activity in the terminal projection site of a fiber system) or antidromic (recording of activity in the cells of origin when their axon terminals or axons are stimulated). Gross stimulation and recording techniques reflect the relationship between groups of neurons; intracellular recordings reflect the relationship between pairs of neurons.

These methods used to study neural connectivity are based on the principle of the neuron as a trophic unit. If an axon is transected, its peripheral parts, including its termination, undergo degeneration. This is referred to as anterograde degeneration. The methods described in 3 above are used to show this type of degeneration. Simultaneously with anterograde degeneration, changes occur in the proximal components of the neuron, namely in the proximal axon, the cell body, and dendrites. These changes are known as retrograde changes.

When considered together, anterograde and retrograde methods allow a detailed mapping of neural connectivity.

Next Page | Previous Page | Section Top | Title Page

URL: http://www.anatomyatlases.org/