The Human Nervous System.
The nervous system is the part of an animal’s body that coordinates its voluntary and involuntary actions and transmits signals between different parts of its body. Nervous tissue first arose in wormlike organisms about 550 to 600 million years ago. In most animal species it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS contains the brain and spinal cord. The PNS consists mainly of nerves, which are enclosed bundles of the long fibers or axons, that connect the CNS to every other part of the body. The PNS includes motor neurons, mediating voluntary movement; the autonomic nervous system, comprising the sympathetic nervous system and the parasympathetic nervous system, which regulate involuntary functions, and the enteric nervous system, which functions to control the gastrointestinal system.
At the cellular level, the nervous system is defined by the presence of a special type of cell, called the neuron, also known as a “nerve cell”. Neurons have special structures that allow them to send signals rapidly and precisely to other cells. They send these signals in the form of electrochemical waves traveling along thin fibers called axons, which cause chemicals called neurotransmitters to be released at junctions called synapses. A cell that receives a synaptic signal from a neuron may be excited, inhibited, or otherwise modulated. The connections between neurons can form neural circuits and also neural networks that generate an organism’s perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support.
Nervous systems are found in most multicellular animals, but vary greatly in complexity. The only multicellular animals that have no nervous system at all are sponges, placozoans and mesozoans, which have very simple body plans. The nervous systems of the radially symmetric organisms the ctenophores (comb jellies) and cnidarians (which include anemones, hydras, corals and jellyfish) consist of a diffuse nerve net. All other animal species, with the exception of a few types of worm, have a nervous system containing a brain, a central cord (or two cords running in parallel), and nerves radiating from the brain and central cord. The size of the nervous system ranges from a few hundred cells in the simplest worms, to around 100 billion cells in humans.
The central nervous system functions to send signals from one cell to others, or from one part of the body to others and to receive feedback. Malfunction of the nervous system can occur as a result of genetic defects, physical damage due to trauma or toxicity, infection or simply of ageing. The medical specialty of neurology studies disorders of the nervous system and looks for interventions that can prevent or treat them. In the peripheral nervous system, the most common problem is the failure of nerve conduction, which can be due to different causes including diabetic neuropathy and demyelinating disorders such as multiple sclerosis and amyotrophic lateral sclerosis.
Neuroscience is the field of science that focuses on the study of the nervous system.
The nervous system derives its name from nerves, which are cylindrical bundles of fibers (the axons of neurons), that emanate from the brain and spinal cord, and branch repeatedly to innervate every part of the body. Nerves are large enough to have been recognized by the ancient Egyptians, Greeks, and Romans, but their internal structure was not understood until it became possible to examine them using a microscope. A microscopic examination shows that nerves consist primarily of axons, along with different membranes that wrap around them and segregate them into fascicles. The neurons that give rise to nerves do not lie entirely within the nerves themselves—their cell bodies reside within the brain, spinal cord, or peripheral ganglia.
All animals more advanced than sponges have nervous systems. However, even sponges, unicellular animals, and non-animals such as slime molds have cell-to-cell signalling mechanisms that are precursors to those of neurons. In radially symmetric animals such as the jellyfish and hydra, the nervous system consists of a nerve net, a diffuse network of isolated cells. In bilaterian animals, which make up the great majority of existing species, the nervous system has a common structure that originated early in the Ediacaran period, over 550 million years ago.
The nervous system contains two main categories or types of cells: neurons and glial cells.
The nervous system is defined by the presence of a special type of cell—the neuron (sometimes called “neurone” or “nerve cell”). Neurons can be distinguished from other cells in a number of ways, but their most fundamental property is that they communicate with other cells via synapses, which are membrane-to-membrane junctions containing molecular machinery that allows rapid transmission of signals, either electrical or chemical. Many types of neuron possess an axon, a protoplasmic protrusion that can extend to distant parts of the body and make thousands of synaptic contacts. Axons frequently travel through the body in bundles called nerves.
Even in the nervous system of a single species such as humans, hundreds of different types of neurons exist, with a wide variety of morphologies and functions. These include sensory neurons that transmute physical stimuli such as light and sound into neural signals, and motor neurons that transmute neural signals into activation of muscles or glands; however in many species the great majority of neurons receive all of their input from other neurons and send their output to other neurons.
Glial cells (named from the Greek for “glue”) are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas. Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons; and to provide guidance cues directing the axons of neurons to their targets. A very important type of glial cell (oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system) generates layers of a fatty substance called myelin that wraps around axons and provides electrical insulation which allows them to transmit action potentials much more rapidly and efficiently.
Anatomy in vertebrates
Diagram showing the major divisions of the vertebrate nervous system.
The nervous system of vertebrates (including humans) is divided into the central nervous system (CNS) and the peripheral nervous system (PNS).
The (CNS) is the major division, and consists of the brain and the spinal cord. The spinal canal contains the spinal cord, while the head contains the brain. The CNS is enclosed and protected by the meninges, a three-layered system of membranes, including a tough, leathery outer layer called the dura mater. The brain is also protected by the skull, and the spinal cord by the vertebrae.
The peripheral nervous system (PNS) is a collective term for the nervous system structures that do not lie within the CNS. The large majority of the axon bundles called nerves are considered to belong to the PNS, even when the cell bodies of the neurons to which they belong reside within the brain or spinal cord. The PNS is divided into somatic and visceral parts. The somatic part consists of the nerves that innervate the skin, joints, and muscles. The cell bodies of somatic sensory neurons lie in dorsal root ganglia of the spinal cord. The visceral part, also known as the autonomic nervous system, contains neurons that innervate the internal organs, blood vessels, and glands. The autonomic nervous system itself consists of two parts: the sympathetic nervous system and the parasympathetic nervous system. Some authors also include sensory neurons whose cell bodies lie in the periphery (for senses such as hearing) as part of the PNS; others, however, omit them.
The vertebrate nervous system can also be divided into areas called grey matter (“gray matter” in American spelling) and white matter. Grey matter (which is only grey in preserved tissue, and is better described as pink or light brown in living tissue) contains a high proportion of cell bodies of neurons. White matter is composed mainly of myelinated axons, and takes its color from the myelin. White matter includes all of the nerves, and much of the interior of the brain and spinal cord. Grey matter is found in clusters of neurons in the brain and spinal cord, and in cortical layers that line their surfaces. There is an anatomical convention that a cluster of neurons in the brain or spinal cord is called a nucleus, whereas a cluster of neurons in the periphery is called a ganglion. There are, however, a few exceptions to this rule, notably including the part of the forebrain called the basal ganglia.
A neuron is called identified if it has properties that distinguish it from every other neuron in the same animal—properties such as location, neurotransmitter, gene expression pattern, and connectivity—and if every individual organism belonging to the same species has one and only one neuron with the same set of properties. In vertebrate nervous systems very few neurons are “identified” in this sense—in humans, there are believed to be none—but in simpler nervous systems, some or all neurons may be thus unique. In the roundworm C. elegans, whose nervous system is the most thoroughly described of any animal’s, every neuron in the body is uniquely identifiable, with the same location and the same connections in every individual worm. One notable consequence of this fact is that the form of the C. elegans nervous system is completely specified by the genome, with no experience-dependent plasticity.
The brains of many molluscs and insects also contain substantial numbers of identified neurons. In vertebrates, the best known identified neurons are the gigantic Mauthner cells of fish. Every fish has two Mauthner cells, located in the bottom part of the brainstem, one on the left side and one on the right. Each Mauthner cell has an axon that crosses over, innervating neurons at the same brain level and then travelling down through the spinal cord, making numerous connections as it goes. The synapses generated by a Mauthner cell are so powerful that a single action potential gives rise to a major behavioral response: within milliseconds the fish curves its body into a C-shape, then straightens, thereby propelling itself rapidly forward. Functionally this is a fast escape response, triggered most easily by a strong sound wave or pressure wave impinging on the lateral line organ of the fish. Mauthner cells are not the only identified neurons in fish—there are about 20 more types, including pairs of “Mauthner cell analogs” in each spinal segmental nucleus. Although a Mauthner cell is capable of bringing about an escape response individually, in the context of ordinary behavior other types of cells usually contribute to shaping the amplitude and direction of the response.
Mauthner cells have been described as command neurons. A command neuron is a special type of identified neuron, defined as a neuron that is capable of driving a specific behavior individually. Such neurons appear most commonly in the fast escape systems of various species—the squid giant axon and squid giant synapse, used for pioneering experiments in neurophysiology because of their enormous size, both participate in the fast escape circuit of the squid. The concept of a command neuron has, however, become controversial, because of studies showing that some neurons that initially appeared to fit the description were really only capable of evoking a response in a limited set of circumstances.
At the most basic level, the function of the nervous system is to send signals from one cell to others, or from one part of the body to others. There are multiple ways that a cell can send signals to other cells. One is by releasing chemicals called hormones into the internal circulation, so that they can diffuse to distant sites. In contrast to this “broadcast” mode of signaling, the nervous system provides “point-to-point” signals—neurons project their axons to specific target areas and make synaptic connections with specific target cells. Thus, neural signaling is capable of a much higher level of specificity than hormonal signaling. It is also much faster: the fastest nerve signals travel at speeds that exceed 100 meters per second.
At a more integrative level, the primary function of the nervous system is to control the body. It does this by extracting information from the environment using sensory receptors, sending signals that encode this information into the central nervous system, processing the information to determine an appropriate response, and sending output signals to muscles or glands to activate the response. The evolution of a complex nervous system has made it possible for various animal species to have advanced perception abilities such as vision, complex social interactions, rapid coordination of organ systems, and integrated processing of concurrent signals. In humans, the sophistication of the nervous system makes it possible to have language, abstract representation of concepts, transmission of culture, and many other features of human society that would not exist without the human brain.
Neurons and synapses
Major elements in synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the wave reaches a synapse, it provokes release of a small amount of neurotransmitter molecules, which bind to chemical receptor molecules located in the membrane of the target cell.
Most neurons send signals via their axons, although some types are capable of dendrite-to-dendrite communication. (In fact, the types of neurons called amacrine cells have no axons, and communicate only via their dendrites.) Neural signals propagate along an axon in the form of electrochemical waves called action potentials, which produce cell-to-cell signals at points where axon terminals make synaptic contact with other cells.
Synapses may be electrical or chemical. Electrical synapses make direct electrical connections between neurons, but chemical synapses are much more common, and much more diverse in function. At a chemical synapse, the cell that sends signals is called presynaptic, and the cell that receives signals is called postsynaptic. Both the presynaptic and postsynaptic areas are full of molecular machinery that carries out the signalling process. The presynaptic area contains large numbers of tiny spherical vessels called synaptic vesicles, packed with neurotransmitter chemicals. When the presynaptic terminal is electrically stimulated, an array of molecules embedded in the membrane are activated, and cause the contents of the vesicles to be released into the narrow space between the presynaptic and postsynaptic membranes, called the synaptic cleft. The neurotransmitter then binds to receptors embedded in the postsynaptic membrane, causing them to enter an activated state. Depending on the type of receptor, the resulting effect on the postsynaptic cell may be excitatory, inhibitory, or modulatory in more complex ways. For example, release of the neurotransmitter acetylcholine at a synaptic contact between a motor neuron and a muscle cell induces rapid contraction of the muscle cell. The entire synaptic transmission process takes only a fraction of a millisecond, although the effects on the postsynaptic cell may last much longer (even indefinitely, in cases where the synaptic signal leads to the formation of a memory trace).
Structure of a typical chemical synapse
There are literally hundreds of different types of synapses. In fact, there are over a hundred known neurotransmitters, and many of them have multiple types of receptors. Many synapses use more than one neurotransmitter—a common arrangement is for a synapse to use one fast-acting small-molecule neurotransmitter such as glutamate or GABA, along with one or more peptide neurotransmitters that play slower-acting modulatory roles. Molecular neuroscientists generally divide receptors into two broad groups: chemically gated ion channels and second messenger systems. When a chemically gated ion channel is activated, it forms a passage that allows specific types of ion to flow across the membrane. Depending on the type of ion, the effect on the target cell may be excitatory or inhibitory. When a second messenger system is activated, it starts a cascade of molecular interactions inside the target cell, which may ultimately produce a wide variety of complex effects, such as increasing or decreasing the sensitivity of the cell to stimuli, or even altering gene transcription.
According to a rule called Dale’s principle, which has only a few known exceptions, a neuron releases the same neurotransmitters at all of its synapses. This does not mean, though, that a neuron exerts the same effect on all of its targets, because the effect of a synapse depends not on the neurotransmitter, but on the receptors that it activates. Because different targets can (and frequently do) use different types of receptors, it is possible for a neuron to have excitatory effects on one set of target cells, inhibitory effects on others, and complex modulatory effects on others still. Nevertheless, it happens that the two most widely used neurotransmitters, glutamate and GABA, each have largely consistent effects. Glutamate has several widely occurring types of receptors, but all of them are excitatory or modulatory. Similarly, GABA has several widely occurring receptor types, but all of them are inhibitory. Because of this consistency, glutamatergic cells are frequently referred to as “excitatory neurons”, and GABAergic cells as “inhibitory neurons”. Strictly speaking this is an abuse of terminology—it is the receptors that are excitatory and inhibitory, not the neurons—but it is commonly seen even in scholarly publications.
One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength. The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor. The NMDA receptor has an “associative” property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell. The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength that are induced by varying conditions, and last for variable periods of time. The reward system, that reinforces desired behaviour for example, depends on a variant form of LTP that is conditioned on an extra input coming from a reward-signalling pathway that uses dopamine as neurotransmitter. All these forms of synaptic modifiability, taken collectively, give rise to neural plasticity, that is, to a capability for the nervous system to adapt itself to variations in the environment.
Reflexes and other stimulus-response circuits
Simplified schema of basic nervous system function: signals are picked up by sensory receptors and sent to the spinal cord and brain, where processing occurs that results in signals sent back to the spinal cord and then out to motor neurons
The simplest type of neural circuit is a reflex arc, which begins with a sensory input and ends with a motor output, passing through a sequence of neurons connected in series. This can be shown in the “withdrawal reflex” causing a hand to jerk back after a hot stove is touched. The circuit begins with sensory receptors in the skin that are activated by harmful levels of heat: a special type of molecular structure embedded in the membrane causes heat to change the electrical field across the membrane. If the change in electrical potential is large enough to pass the given threshold, it evokes an action potential, which is transmitted along the axon of the receptor cell, into the spinal cord. There the axon makes excitatory synaptic contacts with other cells, some of which project (send axonal output) to the same region of the spinal cord, others projecting into the brain. One target is a set of spinal interneurons that project to motor neurons controlling the arm muscles. The interneurons excite the motor neurons, and if the excitation is strong enough, some of the motor neurons generate action potentials, which travel down their axons to the point where they make excitatory synaptic contacts with muscle cells. The excitatory signals induce contraction of the muscle cells, which causes the joint angles in the arm to change, pulling the arm away.
In reality, this straightforward schema is subject to numerous complications. Although for the simplest reflexes there are short neural paths from sensory neuron to motor neuron, there are also other nearby neurons that participate in the circuit and modulate the response. Furthermore, there are projections from the brain to the spinal cord that are capable of enhancing or inhibiting the reflex.
Although the simplest reflexes may be mediated by circuits lying entirely within the spinal cord, more complex responses rely on signal processing in the brain. For example, when an object in the periphery of the visual field moves, and a person looks toward it many stages of signal processing are initiated. The initial sensory response, in the retina of the eye, and the final motor response, in the oculomotor nuclei of the brain stem, are not all that different from those in a simple reflex, but the intermediate stages are completely different. Instead of a one or two step chain of processing, the visual signals pass through perhaps a dozen stages of integration, involving the thalamus, cerebral cortex, basal ganglia, superior colliculus, cerebellum, and several brainstem nuclei. These areas perform signal-processing functions that include feature detection, perceptual analysis, memory recall, decision-making, and motor planning.
Feature detection is the ability to extract biologically relevant information from combinations of sensory signals. In the visual system, for example, sensory receptors in the retina of the eye are only individually capable of detecting “points of light” in the outside world. Second-level visual neurons receive input from groups of primary receptors, higher-level neurons receive input from groups of second-level neurons, and so on, forming a hierarchy of processing stages. At each stage, important information is extracted from the signal ensemble and unimportant information is discarded. By the end of the process, input signals representing “points of light” have been transformed into a neural representation of objects in the surrounding world and their properties. The most sophisticated sensory processing occurs inside the brain, but complex feature extraction also takes place in the spinal cord and in peripheral sensory organs such as the retina.
Intrinsic pattern generation
Although stimulus-response mechanisms are the easiest to understand, the nervous system is also capable of controlling the body in ways that do not require an external stimulus, by means of internally generated rhythms of activity. Because of the variety of voltage-sensitive ion channels that can be embedded in the membrane of a neuron, many types of neurons are capable, even in isolation, of generating rhythmic sequences of action potentials, or rhythmic alternations between high-rate bursting and quiescence. When neurons that are intrinsically rhythmic are connected to each other by excitatory or inhibitory synapses, the resulting networks are capable of a wide variety of dynamical behaviors, including attractor dynamics, periodicity, and even chaos. A network of neurons that uses its internal structure to generate temporally structured output, without requiring a corresponding temporally structured stimulus, is called a central pattern generator.
Internal pattern generation operates on a wide range of time scales, from milliseconds to hours or longer. One of the most important types of temporal pattern is circadian rhythmicity—that is, rhythmicity with a period of approximately 24 hours. All animals that have been studied show circadian fluctuations in neural activity, which control circadian alternations in behavior such as the sleep-wake cycle. Experimental studies dating from the 1990s have shown that circadian rhythms are generated by a “genetic clock” consisting of a special set of genes whose expression level rises and falls over the course of the day. Animals as diverse as insects and vertebrates share a similar genetic clock system. The circadian clock is influenced by light but continues to operate even when light levels are held constant and no other external time-of-day cues are available. The clock genes are expressed in many parts of the nervous system as well as many peripheral organs, but in mammals all of these “tissue clocks” are kept in synchrony by signals that emanate from a master timekeeper in a tiny part of the brain called the suprachiasmatic nucleus.
The central nervous system is protected by major physical and chemical barriers. Physically, the brain and spinal cord are surrounded by tough meningeal membranes, and enclosed in the bones of the skull and spinal vertebrae, which combine to form a strong physical shield. Chemically, the brain and spinal cord are isolated by the so-called blood–brain barrier, which prevents most types of chemicals from moving from the bloodstream into the interior of the CNS. These protections make the CNS less susceptible in many ways than the PNS; the flip side, however, is that damage to the CNS tends to have more serious consequences.
Although nerves tend to lie deep under the skin except in a few places such as the ulnar nerve near the elbow joint, they are still relatively exposed to physical damage, which can cause pain, loss of sensation, or loss of muscle control. Damage to nerves can also be caused by swelling or bruises at places where a nerve passes through a tight bony channel, as happens in carpal tunnel syndrome. If a nerve is completely transected, it will often regenerate, but for long nerves this process may take months to complete. In addition to physical damage, peripheral neuropathy may be caused by many other medical problems, including genetic conditions, metabolic conditions such as diabetes, inflammatory conditions such as Guillain–Barré syndrome, vitamin deficiency, infectious diseases such as leprosy or shingles, or poisoning by toxins such as heavy metals. Many cases have no cause that can be identified, and are referred to as idiopathic. It is also possible for nerves to lose function temporarily, resulting in numbness as stiffness—common causes include mechanical pressure, a drop in temperature, or chemical interactions with local anesthetic drugs such as lidocaine.
Physical damage to the spinal cord may result in loss of sensation or movement. If an injury to the spine produces nothing worse than swelling, the symptoms may be transient, but if nerve fibers in the spine are actually destroyed, the loss of function is usually permanent. Experimental studies have shown that spinal nerve fibers attempt to regrow in the same way as nerve fibers, but in the spinal cord, tissue destruction usually produces scar tissue that cannot be penetrated by the regrowing nerves.