Cells of the Nervous System
- There are two broad classes of cells in the nervous system: neurons, which process information, and glia, which provide the neurons with mechanical and metabolic support.
- Three general categories of neurons are commonly recognized (Peters, Palay, & Webster, 1976). Receptors are highly specialized neurons that act to encodesensory information. For example, the photoreceptors of the eye transform variations in light intensity into electrical and chemical signals that can be read by other nerve cells. It is the receptor cells that begin the process of sensation and perception. Interneurons form the second category of nerve cells. These cells receive signals from and send signals to other nerve cells. Interneurons serve to process information in many different ways and constitute the bulk of the human nervous system. Effectors or motor neurons are the third class of neurons. These cells send signals to the muscles and glands of the body, thereby directly governing the behavior of the organism.
- In all neurons, the cell membrane separates the interior of the cell from the surrounding fluids. This outer membrane is fundamental to the neuronís information processing functions. Once thought to be relatively simple and uniform in structure, the cell membrane is now known to be highly complex and specialized molecular machine that performs a wide variety of roles in cellular function. Further, the membrane has different properties in different specialized functional regions of the neuron
- A typical neuron may be divided into three distinct parts: its cell body, dendrites, and axon (see Figure 3.1). The cell body, or soma, contains the nucleus of the cell and its associated intracellular structures. Dendrites are specialized extensions of the cell body. They function to obtain information from other cells and carry that information to the cell body. Many neurons also have an axon, which carries information from the soma to other cells, but many small cells do not. Axons terminate in endfeet, or terminal boutons (buttons), which transmit information to the receiving cell. Dendrites and axons, both extensions of the cell body, are also referred to as processes.
- The point of communication between one neuron and another is called a synapse. Synapses are generally directional in function, with activity at the end foot of the sending cell (presynaptic cell) affecting the behavior of the receiving cell (postsynaptic cell). In most neurons, the postsynaptic membrane is usually on the cell body or dendrites, but synapses between axons also occur.
- Most neurons have several dendrites and one axon. Because of their multiple processes, these are termed multipolar neurons. Simpler unipolar (one-process) and bipolar (two-process) neurons are much less common in vertebrate than in invertebrate nervous systems.
- A primary function of neurons is to process information and to integrate the influences of the cells from which they receive input. In the human brain, it is not unusual for a single neuron to receive input at 20,000 or 30,000 synapses, Thus, the information-processing functions of the neurons of the brain can be quite complex.
- It is often useful to distinguish between types of cells on the basis of their appearance, as form can provide clues about function. Perhaps the most important distinction is between neurons with and neurons without long axons.
- The long-axoned cells, called principal neurons, transmit information over long distances from one brain region to another (Sheperd,1979). Principal neurons provide the pathways of communication within the nervous system.
- In contrast local circuit neurons, which lack long axons, must exert all their effects in the local region of their cell bodies and dendrites. They are located in brain areas served by the long-axoned principal neurons and act to affect the activity in these pathways. Local circuit neurons perform integrative and modulating functions in local brain regions.
- The size and shape of neurons are often related. Principal neurons, with their long axons, usually have large cell bodies. In part, this is because the axon is dependent upon the cell body for metabolic energy and for the proteins that it needs to function and maintain itself. Furthermore, cells with large dendritic trees, like the Purkinje cell shown in Figure 3.3, also tend to have large cell bodies. In contrast, the local circuit neurons, with their short dendrites and small axons (when present), usually have small, compact cell bodies.
- Dendrites may be thought of as continuations of the cell bodyís membrane, expending that sensitive receptive surface into the surrounding nervous tissue. It is not surprising to find that the pattern of dendritic branching differs widely among cells and reflects the functions that the cell performs. In some cases, the functional properties of a neuron can be completely predicted from its pattern of dendritic spread. The dendrites, with their thin, branching, treelike forms, greatly increase the opportunity for synaptic connections in brain tissue.
- Electron microscopy confirms the concept of dendrites as extensions of the cell body. The same types of intracellular substructures that characterize the cell body of a neuron are also present in dendrites.
- Many types of neurons have dendrites with a special form of synaptic connection, dendritic spines. These are small (1-2 um), thornlike protuberances from the dendrite that form the postsynaptic element of most synapses in the brain. Figure 3.4 shows one view of a dendrite with dendritic spines as seen in high-powered light microscopy and Golgi staining. The dendritic spines appear to reach out to make contact with nearby axons.
- The pattern of the dendritic spines changes over the length of the dendrite. Near the cell body, the spines are usually small and relatively simple enlargements protruding slightly from the side of the dendrite. At greater distances, the spines become larger and more elaborate. Spines emerge from the dendrite and expand, sometimes splitting into a double spine with multiple synapses. At the very least, spines increase the synaptic surface of the dendrite, allowing a maximum of synaptic content with a minimum of dendritic volume.
- About 80 percent of all excitatory synapses (those acting to evoke activity in the postsynaptic cell) are onto dendritic spines; the remainder involving other parts of the dendrite. In contrast, fewer than one third of all inhibitory synapses involve spines, and when they do, they are coupled with an excitatory synapse on the same spine. The specific reasons for this arrangement are a matter of growing interest.
- It has also been suggested that dendritic spines are modifiable structures that may change with learning and other factors. Whatever their functional role may be, dendritic spines are a major anatomical feature of many classes of neurons in the human nervous system.
The Cell Body
The cell body integrates synaptic input and determines the message to be transmitted to other cells by the axon, but that is not its only function. The cell body also is responsible for a variety of complex biochemical processes. For example, the cell body contains the metabolic machinery necessary to transform glucose into high-energy compounds that supply the energy needs of other parts of the neuron. Furthermore, the highly active proteins that serve as chemical messengers between cells are manufactured and packaged in the cell body. The cell body contains a number of smaller, specialized substructures, called organelles, or little organs, which carry out many of the cellís functions. Figure 3.5 illustrates the organelles of a typical neuron.
- Supplying metabolic energy to the cell in form that can be easily utilized is a primary role of the mitochondria. These organelles have their own outer membrane encasing a folded, internal membrane. The major source of energy for the nervous system is the sugar glucose, which is derived from carbonhydrate foodstuffs. Mitochondria contain the enzymes necessary to transform glucose into high-energy compounds, primarily adenosine triphosphate (ATP). ATP molecules may then be transported to other regions of the cell where their energy is utilized.
- The manufacture of neuronal active compounds and other large protein molecules within the cell body is more complex. The process protein synthesis begins in the nucleus of the cell. The nucleus of a neuron is separated from the intracellular fluid and other organelle of the cell, containing the genetic information that guides cellular function. The genetic template is stored as coded strings of deoxyribonucleic acid (DNA). Each DNA molecule holds the genetic codes for all the cells in the body; only a selected part of this genetic blueprint is utilized by nerve cells . The nucleus begins the process of building protein molecules by transcribing the relevant portion of DNA code onto a complementary molecule of ribonucleic acid (RNA). RNA molecules then are released by the nucleus into the intracellular fluid surrounding it, where the process of protein synthesis actually takes place.
- The nucleolus is a separate structure within the nucleus, which also is involved in the process of protein synthesis. However the nucleolus does not manufacture proteins directly. Instead, it builds molecular complexes, called ribosomes, that are involved in protein synthesis. Ribosomes are complexes of RNA and protein that are ejected from the nucleolus and nucleus into the cell body, where they do their work.
Endoplasmic Reticulum and Golgi Apparatus
- Two other organelles are primarily responsible for the cellular manufacture of proteins, the endoplasmic reticulum and the Golgi apparatus. Together, they form a miniature manufacturing and packaging plant. The endoplasmic reticulum is a system of tubes, vesicles, and sacs constructed from membranes similar to those surrounding the neuron. The rough endoplasmic reticulum is the initial segment of structure that begins to build protein molecules; it gains its rough appearance from the presence of large numbers of ribosomes bound to its surface. The ribosomes of the rough endoplasmic reticulum construct large segments of protein molecules in the sequence of steps prescribed by the RNA released by the nucleus of the cell. These segments of the protein molecule are moved down through endoplasmic reticulum much like a product being assembled on an industrial assembly line. When completed, the segments are released into the smooth endoplasmic reticulum, which lacks ribosomes, and are transported by it to the Golgi apparatus.
- The Golgi apparatus- named in honor of Camillo Golgi- is a complex of membranes that completes the assembling of the protein and encloses the resulting molecules in their own membrane for release into the cell. It is important that the proteins be packaged in this way because they have strong effect on neural function. when enclosed in a sphere built of membrane, a vesicle, the proteins may be moved safely to the portion of the cell in which they will eventually be used. For example, the neurotransmitters that are released by a cell into a synapse are manufactured by the endoplasmic reticulum and Golgi apparatus in the cell body, encased in a vesicle, and then transported down the length of the axon to the synapse where they eventually will be used.
- The axon of a neuron arises from the cell body and extends to the region or regions of synaptic contact. Axons are specialized processes that are characterized by having an excitable membrane, a membrane that is capable of generating or propagating an action potential (Hille, 1984; Katz, 1966). An action potential is a distinctive length of the axon.
- Usually, cells have only one axon, but it may give off collaterals, or branches, to carry the action potential to more than one region of the brain. Figure 3.6 shows a Golgi stain of a single neuron located in the stalk of the brain that gives off numerous collaterals and thereby affects activity in many brain areas. This degree of branching is far from typical , however. Most cells with prominent axons have far fewer, if any, collaterals.
- The axon emerges from the cell body in a tapering cone of membrane that forms the axon hillock. This structure is very distinct from the rest of the cell body when examined microscopically; it is completely devoid of the ribosomes and endoplasmic reticulum that characterize the rest of the cell body and the neighboring portions of the dendrites. Instead, there are numerous microtubules and microfilaments, which form the basis of a transportation system for the axon, aiding in the movement of substances from the cell body to the endfeet.
- As an axon approaches its synaptic targets, it often branches into a number of smaller processes, each terminating in an endfoot. One schematic view of the axon branching into its terminal boutons was shown in Figure 3.2. The endfeet themselves may be seen in Figure 3.7. Within each endfoot are both mitochondria and synaptic vesicles. The synaptic vesicles contain neurotransmitter substances, which are released into the space between the presynaptic membrane of the endfoot and the postsynaptic membrane of the receiving cell. The space between the presynaptic and postsynaptic membrane is called the synaptic cleft.
The Cell Membrane
- The membrane that separates the neuron from other cells and from the extracellular fluid is of extreme importance in understanding neuronal function. All information received by a neuron must enter through this membrane; all messages that a neuron may send to other cells must depart through it as well. Much has been learned about cell membrane, in particular neuronal membranes, in the past two decades. The neuronal membrane is a complex molecular machine with a number of important adaptations that perform specific information-processing function for the cell.
- The neural membrane is a very old invention in evolution, one that was so successful that it has remained unchanged in both invertebrate and vertebrate nervous systems. Its major structural components are phospholipids, or fatty acids. These long, thin molecules have read that is hydrophilic, or "water loving," and a tail that is hydrophobic, or "water hating." When phospholipids are dissolved in an appropriate agent (such as benzene) and a few drops are placed on a surface of water, a remarkable biochemical self-organizing effect occurs; each molecule orients itself with its hydrophilic head on the waterís surface and itís hydrophobic tail extended away from the water into the air. Figure 3.9 illustrates a number of phospholipid molecules organizing themselves at the water-air boundary. Since both the intracellular and extracellular fluids are solutions of water and salts, one might imagine a cellular membrane made up of two layers of phospholipids, as illustrated in Figure 3.10.
- In this two-layer model, both the inner and outer surfaces of the membrane are composed of the hydrophilic heads of phospholipid molecules; the inner portion of the membrane consists of the interleaved hydrophobic tails of the fatty acids. There is ample evidence supporting this view of the membrane . For example, if a piece of membrane of a known area is broken up into its constituent phospholipid molecules and these molecules are then floated on water, the resulting area of the recognized molecules is exactly twice that of the original piece of membrane. The inner and outer layers of the biological membrane have become one on the surface of the water.
- The second major feature of the membrane is the protein molecules that are embedded within it. Proteins are complex organic molecules formed from strings of amino acids. Protein molecules within the membrane are termed integral proteins, which function as specialized biochemical machines within the membrane. The integral proteins provide a number of mechanisms that link the interior environment of the cell with its exterior environment. One function of these proteins is transport, selectively moving particular molecules such as glucose across the membrane. Integral proteins are particularly important at synapses, where a variety of specialized functions are performed. The functional aspects of membrane proteins are discussed in later chapters.
- In addition to the integral membrane proteins, there are also important peripheral proteins. These large molecules adhere to the inner or outer membrane surface, where they serve a number of specialized roles.
Glia and Other Supporting Cells
- The focus of attention in studying the biological basis of behavior is on neurons and their activities, but neurons are not the only cells in the central nervous system. They are supported by glia cells, which appear to perform a variety of housekeeping functions in the brain (Fawcett, 1981). The term glia means "glue," a reflection of the fact that glial cells really do hold the brain together, occupying the space between neurons. Glia are usually very small cells, but there are a great many of them. Thus, although a little more than one half of the brainís weight is contributed by glial cells, they outnumber neurons by a factor of between 10 and 50 (Figure 3.11).
- There are two types of glial cells in the nervous system: the large-bodied macroglia and the smaller microglia. There are two classes of macroglia in the central nervous system: astrocytes and oligodendrocytes. Figure 3.12 shows astrocytes, a numerous type of glia named for their star-shaped appearance when Golgi-stained. When examined at greater magnification, these small cells show a characteristics lack of organelles within their cell bodies. Apparently, the astrocytes are not heavily engaged in synthetic functions, such as building proteins. It was once thought that astrocytes formed a major part of the blood-brain barrier, which protects the brain from a variety of substances in the general circulation, but recent evidence suggests that this is not true. Astrocytes are now believed to provide structural support for the neurons of the brains and aid in the repair of neurons following damage to the brain. They also regulated the flow of ions and larger molecules in the region of the synapses, a fact of unknown significance.
- A second type of macroglia cells are the oligodendrocytes. These are small cells that lack the spidery processes of the astroglia. Oligendrocytes differ from astrocytes in their cell bodies contain a large number of organelles. They also contain many microtubules that are arranged in parallel arrays. Oligodendrocytes may serve a number of functional roles within the central nervous system, but only one is known with certainty. The oligendrocytes produce myelin, which surrounds the axons of many neurons. This insulating coating is called a myelin sheath.
- Outside the central nervous system. along the peripheral nerves that connect the brain and spinal cord with the muscles, glands, and sensory organs of the body, there is another type of supporting cell that is similar in many ways to the oligendrocytes. This is the Shwann cell, illustrated in Figure 3.13. In the developing nervous system, the Shwann cell first encircles an axon, then wraps itself around the neuron, building a myelin sheath (see Figure 3.14). As it moves, the cytoplasm is pushed forward, leaving only the membrane of the Shwann cell wrapped around the once-naked axon. Myelination greatly increases the speed with which action potentials are carried along an axon.
- In contrast, the microglia perform "housekeeping" functions within the central nervous system. Among their duties is the removal of dead cells within the brain. (Something like 100,000 of the brainís 100 billion neurons are estimated to die each day, a fact that accounts for the slight shrinking of the brain in aging.)
- Neurons are the information-processing cells of the nervous system. They are categorized as receptors, interneurons, or effectors, depending on their function. The dendrites of a neuron provide an extended receptive surface for the cell, increasing greatly the number of synaptic inputs. Many dendrites have dendritic spines at their more distant synapses.
- The cell body integrates information from the dendrites and other synaptic inputs in determining the messages to be transmitted to other cells through its axon. The cell body also contains a number of specialized substructures: its nucleus, mitochondria, ribosomes, endoplasmic reticulum, and Golgi apparatus. These substructures either serve metabolic functions or build complex molecules for use in other regions of the cell.
- The axon carries messages in the form of action potentials from the cell body to its endfeet, which synapse upon other neurons or effector organs. Cells with long axons are called principal neurons. These cells establish the pattern of connectivity within the nervous system. Cells with only short or no axons are called local circuit neurons; they affect activity within their own immediate vicinity.
- The cell membrane, completely separating the cell from its external environment, is composed of a phospholipid bilayer in which large protein molecules may be embedded. The proteins serve as molecular machines that are responsible for all transactions between the neuron and its environment.
- The glia are the other type of cells within the central nervous system. There are a great many glial cells, but rather little is known about their functions. They are presumed to serve primarily supportive roles for the neurons. One type of glia, the oligodendrocytes, produce the myelin sheaths that insulate the axons of many central nervous system neurons.