Organization of the Nervous System

The nervous system can be divided into central, peripheral, and autonomic nervous systems

The manner in which the nervous system is subdivided is somewhat arbitrary. All elements of the nervous system work closely together in a way that has no clear boundaries. Nevertheless, the traditional definitions of the subdivisions provide a useful framework for talking about the brain and its connections, and are important if only for that reason.

The central nervous system (CNS) consists of the brain and spinal cord ( Table 10-1 ). It is covered by three “membranes”—the meninges. The outer membrane is the dura mater; the middle is the arachnoid; and the delicate inner membrane is called the pia mater. Within the CNS, some neurons that share similar functions are grouped into aggregations called nuclei. The CNS can also be divided into gray matter, which contains neuron cell bodies, and white matter, which is rich in myelin (see pp. 199–201 ).

The peripheral nervous system (PNS) consists of those parts of the nervous system that lie outside the dura mater (see Table 10-1 ). These elements include sensory receptors for various kinds of stimuli, the peripheral portions of spinal and cranial nerves, and all the peripheral portions of the autonomic nervous system. The sensory nerves that carry messages from the periphery to the CNS are termed afferent nerves (from the Latin ad + ferens [carrying toward]). Conversely, the peripheral motor nerves that carry messages from the CNS to peripheral tissues are called efferent nerves (from the Latin ex + ferens [carrying away]). Peripheral ganglia are groups of nerve cells concentrated into small knots or clumps that are located outside the CNS.

The autonomic nervous system (ANS) is that portion of the nervous system that regulates and controls visceral functions, including heart rate, blood pressure, digestion, temperature regulation, and reproductive function. Although the ANS is a functionally distinct system, it is anatomically composed of parts of the CNS and PNS (see Table 10-1 ). Visceral control is achieved by reflex arcs that consist of visceral afferent (i.e., sensory) neurons that send messages from the periphery to the CNS, control centers in the CNS that receive this input, and visceral motor output. Moreover, visceral afferent fibers typically travel together with visceral efferent fibers.

Each area of the nervous system has unique nerve cells and a different function

Nervous tissue is composed of neurons and neuroglial cells. Neurons vary greatly in their structure throughout the nervous system, but they all share certain features that tailor them for the unique purpose of electrical communication (see Chapter 12 ). Neuroglial cells, often simply called glia, are not primary signaling cells and have variable structures that are suited for their diverse functions (see Chapter 11 ).

The human brain contains ~10 ¹¹ neurons and slightly more glial cells. Each of these neurons may interact with thousands of other neurons, which helps explain the awesome complexity of the nervous system.

Few, if any, of the receptors, ion channels, or cells in the human brain are unique to humans. The unparalleled capabilities of the human brain are presumed to result from its unique patterns of connectivity and its large size.

The brain's diverse functions are the result of tremendous regional specialization. Different brain areas are composed of neurons that have special shapes, physiological properties, and connections. One part of the brain, therefore, cannot substitute functionally for another part that has failed. Any compensation of neural function by a patient with a brain lesion (e.g., a stroke) reflects enhancement of existing circuits or recruitment of latent circuits. A corollary is that damage to a specific part of the brain causes predictable symptoms that enable a clinician to establish the anatomical location of the problem, a key step in diagnosis of neurological diseases.

The neuron doctrine first asserted that the nervous system is composed of many individual signaling units—the neurons

In 1838, Schleiden and Schwann proposed that the nucleated cell is the fundamental unit of structure and function in both plants and animals. They reached this conclusion by microscopic observation of plant and animal tissues that had been stained to reveal their cellular composition. However, the brain proved to be more difficult to stain than other tissues, and until 1885, when Camillo Golgi introduced his silver-impregnation method, “the black reaction,” there was no clear indication that the brain is composed of individual cells. The histologist Santiago Ramón y Cajal worked relentlessly with the silver-staining method and eventually concluded that not only is nervous tissue composed of individual cells, but the anatomy of these cells also confers a functional polarization to the passage of nervous signals; the tapering branches near the cell body are the receptive end of the cell, and the long-axis cylinder conveys signals away from the cell. In the absence of any reliable physiological evidence, Ramón y Cajal was nevertheless able to correctly anticipate how complex cell aggregates in the brain communicate with each other.

The pathologist Heinrich von Waldeyer referred to the individual cells in the brain as neurons. He wrote a monograph in 1891 that assembled the evidence in favor of the cellular composition of nervous tissue, a theory that became known as the neuron doctrine. It is ironic that Golgi, whose staining technique made these advances possible, never accepted the neuron doctrine, and he argued vehemently against it when he received his Nobel Prize along with Ramón y Cajal in 1906. N10-1 The ultimate proof of the neuron doctrine was established by electron microscopic observations that definitively demonstrated that neurons are entirely separate from one another, even though their processes come into very close contact.

Nerve cells have four specialized regions: cell body, dendrites, axon, and presynaptic terminals

Neurons are specialized for sending and receiving signals, a purpose reflected in their unique shapes and physiological adaptations. The structure of a typical neuron can generally be divided into four distinct domains: (1) the cell body, also called the soma or perikaryon; (2) the dendrites; (3) the axon; and (4) the presynaptic terminals ( Fig. 10-1 ). The shape and organelle composition of these domains depends strongly on their cytoskeleton, which consists of three fibrillary structures: neurofilaments (i.e., intermediate filaments; see p. 23 ), microtubules (see pp. 23–25 ), and thin filaments (see pp. 25–28 ). The cytoskeleton—especially the microtubules and thin filaments, is dynamic and imbues axons and dendrites with the capacity to change shape, a plasticity believed to participate in the synaptic alterations associated with learning and memory.

The cytoskeleton helps compartmentalize the neuron and also provides the tracks along which material travels between different parts of the neuron

Neurons are compartmentalized in both structure and function. Dendrites are tapered, have limited length, and contain neurotransmitter receptor proteins in their membranes. Axons can be very long and have a high density of Na ⁺ channels. Dendrites and the cell body contain messenger RNA, ribosomes, and a Golgi apparatus.

How does this compartmentalization come about? The molecular orientation of microtubules (see pp. 23–25 ) together with microtubule-associated proteins (MAPs) play important roles in dictating the vectorial transport of organelles and proteins. (Note that these MAPs are totally unrelated to the mitogen-activated protein [MAP] kinase; see p. 69. ) Two major classes of MAPs are found in the brain: high-molecular-weight proteins such as MAP-1 and MAP-2 and lower-molecular-weight tau proteins. Both classes of MAPs associate with microtubules and help link them to other cell components. MAP-2 is most abundant in dendrites, where it may assist in dendrite formation. Tau proteins are confined to axons; their suppression in cultured neurons prevents formation of the axon without altering formation of the dendrites. Hyperphosphorylated tau proteins can assemble into pathological aggregates called neurofibrillary tangles, which are a hallmark of Alzheimer Disease.

The polarization of microtubules (see pp. 23–25 ) helps to create remarkable morphological and functional divisions in neurons. In axons, microtubules assemble with their plus ends pointed away from the cell body; this orientation polarizes the flow of material into and out of the axon. The cytoskeletal “order” provided by the microtubules and the MAPs helps define what should or should not be in the axonal cytoplasm. In dendrites, microtubules do not have a consistent orientation, which gives dendrites a greater functional similarity to the soma and perhaps their tapered shape.

The neuron cell body is the main manufacturing site for the membrane proteins and membranous organelles that are necessary for the structural integrity and function of its processes. Axons have little or no intrinsic protein synthetic ability, whereas dendrites have some free ribosomes and are able to engage in limited protein production. The transport of proteins from the cell body all the way to the end of long axons is a challenging task. The neuron also has a second task: moving various material in the opposite direction, from presynaptic terminals at the end of the axon to the cell body. The neuron solves these problems by using two distinct mechanisms for moving material to the presynaptic terminals in an “anterograde” direction and a third mechanism for transport in the opposite or “retrograde” direction ( Table 10-2 ).

Fast Axoplasmic Transport

If the flow of materials from the soma to the distant axon terminus were left to the whims of simple diffusion, their delivery would be far too slow to be of practical use. It could take months for needed proteins to diffuse to the end of an axon, and the presynaptic terminals are high-volume consumers of these molecules. To overcome this difficulty, neurons exploit a rapid, pony express–style system of conveyance known as fast axoplasmic transport (see Table 10-2 ). Membranous organelles, including vesicles and mitochondria, are the principal freight of fast axoplasmic transport. The proteins (some associated with RNA), lipids, and polysaccharides that move at fast rates in axons do so because they have caught a ride with a membranous organelle (i.e., they are sequestered inside the organelle or bound to or inserted into the organellar membrane). The peptide and protein contents of dense-core secretory granules, which are found in the presynaptic axonal terminals, are synthesized as standard secretory proteins (see pp. 34–35 ). Thus, they are cotranslationally inserted across the membranes of the rough endoplasmic reticulum and subsequently processed in the cisternae of the Golgi complex. They are shipped to the axon in the lumens of Golgi-derived carrier vesicles.

Organelles and vesicles, and their macromolecule payloads, move along microtubules (see p. 23 ) with the help of a microtubule-dependent motor protein called kinesin ( Fig. 10-2 A ). The kinesin motor (see p. 25 ) is itself an ATPase that produces vectorial movement of its payload along the microtubule. This system can move vesicles down the axon at rates of up to 400 mm/day; variations in cargo speed simply reflect more frequent pauses during the journey. Kinesins always move toward the plus end of microtubules (i.e., away from the cell body), and transport function is lost if the microtubules are disrupted. The nervous system has many forms of kinesin that recognize and transport different cargo. It is not known how the motor proteins recognize and attach to their intended payloads.