Lecture Outline for Campbell/Reece Biology, 8th Edition

Chapter 49 Nervous Systems Lecture Outline Overview: Command and Control System The human brain contains an estimated 1011 (100 billion) neurons. The circuits that interconnect these brain cells are enormously complex. Recent technologies such as functional magnetic resonance imaging (fMRI) can record brain activity from outside a person’s skull. The brain is scanned with electromagnetic waves, and changes in blood oxygen levels at sites of neuronal activity generate a signal. A computer then uses the data to construct a three-dimensional map of the subject’s brain while the subject does various tasks. Scientists look for correlations between particular tasks and activity in specific regions of the brain. The ability to sense and react originated billions of years ago with prokaryotes that could detect changes in their environment and respond in ways that enhanced their survival and reproductive success. For example, bacteria continue to move in a particular direction as long as they encounter increasing concentrations of a food source. Later, modification of simple recognition and response processes provided multicellular organisms with a mechanism for communication between cells of the body. By the time of the Cambrian explosion, more than 500 million years ago, systems of neurons that allowed animals to sense and move rapidly were present in essentially their current forms. Concept 49.1 Nervous systems consist of circuits of neurons and supporting cells. In most animals with nervous systems, clusters of neurons perform specialized functions. Such clustering is absent in the cnidarians, the simplest animals with nervous systems. In cnidarians, a series of interconnected nerve cells form a diffuse nerve net that controls the contraction and expansion of the gastrovascular cavity. In more complex animals, the axons of multiple nerve cells may be bundled to form nerves. Nerves channel and organize information that flows along specific routes through the nervous system. Sea stars have a set of radial nerves connecting to a central nerve ring. Within each arm, the radial nerve is linked to a nerve net from which it receives input and to which it sends signals controlling motor activity. Such an arrangement allows for the control of elaborate movements. Animals with elongated, bilaterally symmetrical bodies have more specialized nervous systems. Such animals exhibit cephalization, the clustering of sensory neurons and interneurons at the anterior end. One or more nerve cords extending toward the posterior end connect these structures with nerves elsewhere in the body. In nonsegmented worms like the planarian, a small brain and longitudinal nerve cords make up the simplest clearly defined central nervous system (CNS). The entire nervous system of such animals can be constructed from only a small number of cells. In the nematode Caenorhabditis elegans, an adult worm contains exactly 302 neurons, no more and no fewer. In more complex invertebrates, such as annelids and arthropods, the number of neurons is much greater. Behavior is regulated by more complicated brains and by ventral nerve cords containing ganglia, segmentally arranged clusters of neurons. Within an animal group, nervous system organization often correlates with lifestyle. Sessile and slow-moving molluscs, such as clams and chitons, have relatively simple sense organs and little or no cephalization. Active predatory molluscs, such as octopuses and squids, have the most sophisticated nervous systems of any invertebrate. In vertebrates, the brain and the spinal cord form the CNS; the nerves and ganglia make up the peripheral nervous system (PNS). Regional specialization is a hallmark of both systems. The brain and spinal cord of the vertebrate CNS have tightly coordinated activities. The brain integrates the complex behavior of vertebrates. The spinal cord conveys information to and from the brain and generates basic patterns of locomotion. The spinal cord also acts independently as part of the simple nerve circuits that produce reflexes, the body’s automatic responses to stimuli. A reflex protects the body by triggering a rapid, involuntary response to a particular stimulus, such as pulling your hand away from a hot stove. In vertebrates, the spinal cord runs along the dorsal side of the body. Segmental ganglia are present just outside the spinal cord. An underlying segmental organization is apparent in the arrangement of neurons within the spinal cord. The brain and spinal cord of vertebrates derive from the chordate characteristic of a hollow dorsal embryonic nerve cord. During development, the hollow cavity of the embryonic nerve cord is transformed into the narrow central canal of the spinal cord and the ventricles of the brain. The central canal and the four ventricles are filled with cerebrospinal fluid, formed in the brain by filtration of the blood. The cerebrospinal fluid circulates slowly through the central canal and the ventricles and then drains into the veins, bringing nutrients and hormones to the brain and clearing wastes. In mammals, the cerebrospinal fluid cushions the brain and spinal cord by circulating between layers of connective tissue that surround the CNS. In addition to these fluid-filled spaces, the brain and the spinal cord contain gray matter and white matter. Gray matter consists of mainly neuron cell bodies, dendrites, and unmyelinated axons. White matter contains bundled axons with myelin sheaths, making them whitish. White matter is on the outside of the spinal cord, linking the CNS to the sensory and motor neurons of the PNS. White matter in the brain is on the inside, signaling between neurons in learning, emotion, processing of sensory information, and generating commands. A variety of glia are present throughout the vertebrate brain and spinal cord. Ependymal cells line the ventricles and have cilia that circulate cerebrospinal fluid. Microglia protect the nervous system from invading microorganisms. Oligodendrocytes and Schwann cells function in axon myelination, a critical activity in the vertebrate nervous system. Astrocytes have the most diverse set of functions: They provide structural support for neurons and regulate the extracellular concentrations of ions and neurotransmitters. Astrocytes can respond to activity in neighboring neurons by facilitating information transfer at synapses and, in some instances, releasing neurotransmitters. Astrocytes adjacent to active neurons cause nearby blood vessels to dilate, increasing blood flow to the area and enabling the neurons to obtain oxygen and glucose more quickly. During development, astrocytes induce cells that line the capillaries in the CNS to form tight junctions. The result is the blood-brain barrier, which restricts the passage of most substances into the CNS and permits tight control of the extracellular chemical environment of the brain and spinal cord. Radial glia play a critical role in the embryonic development of the nervous system, forming tracks along which newly formed neurons migrate from the neural tube, the structure that gives rise to the CNS. Both radial glia and astrocytes can also act as stem cells, generating neurons and additional glia and offering a potential way to replace neurons and glia that are lost to injury or disease. The PNS transmits information to and from the CNS and regulates a vertebrate’s movement and internal environment. Sensory information reaches the CNS along afferent PNS neurons. After information is processed within the CNS, instructions travel to muscles, glands, and endocrine cells along efferent PNS neurons. The vertebrate PNS consists of left-right pairs of cranial and spinal nerves and their associated ganglia. The cranial nerves originate in the brain and terminate mostly in organs of the head and upper body. The spinal nerves originate in the spinal cord and extend to parts of the body below the head. Most of the cranial nerves and all of the spinal nerves contain both afferent and efferent neurons. The olfactory nerve is afferent, dedicated to conveying sensory information for olfaction, the sense of smell. The efferent branch of the PNS is made up of the motor system and the autonomic nervous system. The motor system consists of neurons that carry signals to skeletal muscles in response to external stimuli. Although the motor system is subject to conscious control, much skeletal muscle activity is actually controlled by the brain stem or by reflexes mediated by the spinal cord. The autonomic nervous system regulates the internal environment by involuntary control of smooth and cardiac muscles and the organs of the digestive, cardiovascular, excretory, and endocrine systems. Three divisions—sympathetic, parasympathetic, and enteric—make up the autonomic nervous system. The sympathetic and parasympathetic divisions function antagonistically in regulating organ function. The sympathetic division is responsible for arousal and energy generation (the fight-or-flight response). With stimulation of this division, the heart beats faster, the liver converts glycogen to glucose, digestion is inhibited, and secretion of epinephrine from the adrenal medulla is stimulated. Activation of the parasympathetic division generally causes opposite responses that promote calming and a return to self-maintenance functions (“rest and digest”). Increased activity in the parasympathetic division lowers heart rate, increases glycogen production, and enhances digestion. The overall functions of the sympathetic and parasympathetic divisions are reflected in the location of neurons in each division and the neurotransmitters that these neurons release. The enteric division consists of networks of neurons in the digestive tract, pancreas, and gallbladder. Neurons of the enteric division control secretion and smooth muscle contraction to produce peristalsis. The enteric division is regulated by the sympathetic and parasympathetic divisions. The somatic and autonomic nervous systems cooperate to maintain homeostasis. For example, if body temperature drops, the hypothalamus signals the autonomic nervous system to constrict surface blood vessels, reducing heat loss. At the same time, the hypothalamus signals the somatic nervous system to cause shivering, increasing heat production. Concept 49.2 The vertebrate brain is regionally specialized. In all vertebrates, three bilaterally symmetrical, anterior bulges of the neural tube—the forebrain, midbrain, and hindbrain—form as the embryo develops. By the fifth week of embryonic development in humans, the three primary bulges have formed five brain regions. Three of these regions, derived from the midbrain and the hindbrain, give rise to the brain stem, a set of structures that form the lower part of the brain. The hindbrain also gives rise to another major brain center, the cerebellum. As embryogenesis proceeds, the most profound changes in the human brain occur in the telencephalon, the region of the forebrain that gives rise to the adult cerebrum. Rapid growth of the telencephalon causes the outer portion of the cerebrum, called the cerebral cortex, to extend over and around much of the rest of the brain. Major centers that develop from the diencephalon are the thalamus, hypothalamus, and epithalamus. The brain stem functions in homeostasis, coordination of movement, and conduction of information to and from higher brain centers. The adult brain stem consists of the midbrain, the pons, and the medulla oblongata or medulla. The medulla and the pons transfer sensory information and motor instructions between the PNS and the midbrain and forebrain. They also help coordinate large-scale body movements, such as running or climbing. In carrying instructions about the movement from cell bodies in the midbrain and forebrain to synapses in the spinal cord, most axons cross in the medulla from one side of the CNS to the other. As a result, the right side of the brain controls much of the movement of the left side of the body, and vice versa. The midbrain contains centers that receive and integrate different types of sensory information, sending coded sensory information along neurons to specific regions of the forebrain. Sensory axons involved in hearing terminate in or pass through the midbrain on their way to the cerebrum. In nonmammalian vertebrates, portions of the midbrain form prominent optic lobes that may be the only visual centers. In mammals, vision is integrated in the cerebrum, not the midbrain. The mammalian midbrain coordinates visual reflexes, such as the peripheral vision reflex, in which the head turns to an approaching object without forming an image of it. Signals from the brain stem affect attention, alertness, appetite, and motivation. The medulla contains centers that control several automatic, homeostatic functions, including breathing, heart and blood vessel activity, swallowing, vomiting, and digestion. The pons also participates in some of these activities; for example, it regulates the breathing centers in the medulla. Axons from the brain stem reach many areas of the cerebral cortex and cerebellum, releasing neurotransmitters such as norepinephrine, dopamine, serotonin, and acetylcholine. The brain stem and cerebrum control arousal and sleep. Arousal is a state of awareness of the external world; sleep is a state in which external stimuli are received but not consciously perceived. Centers in the brain stem control arousal and sleep. The reticular formation, a diffuse network of neurons in the core of the brain stem, acts as a sensory filter to choose which information reaches the cerebral cortex. The brain often ignores certain stimuli while actively processing other inputs. The pons and medulla contain centers that cause sleep when stimulated, and the midbrain has a center that causes arousal. All birds and mammals show characteristic sleep/wake cycles regulated by melatonin, a hormone produced by the pineal gland. Peak melatonin secretion occurs at night. Melatonin has been promoted as a dietary supplement to treat jet lag, insomnia, seasonal affective disorder, and depression. Melatonin is synthesized from serotonin, which itself may be the neurotransmitter of the sleep-producing centers. Serotonin in turn is synthesized from the amino acid tryptophan. Because tryptophan levels are relatively high in milk, drinking milk before bedtime may promote sleep by increasing the production of serotonin and melatonin. Sleep is essential for survival. Furthermore, sleep is an active state, at least for the brain. EEG recordings show that the frequency of brain waves changes as the brain progresses through the distinct stages of sleep. Sleep and dreams may be involved in the consolidation of learning and memory. Regions of the brain activated during a learning task become active again during sleep. Some animals display evolutionary adaptations that allow for substantial activity during sleep. Bottlenose dolphins, which sleep with one eye open and one eye closed, swim while sleeping, rising to the surface to breathe air. EEG recordings from the hemispheres of sleeping dolphins show that dolphins sleep with only one brain hemisphere at a time. The cerebellum coordinates movements and balance. The cerebellum receives sensory information about joint position and muscle length, information from the auditory and visual systems, and input about motor commands issued by the cerebrum. Information from the cerebrum passes first to the pons and from there to the cerebellum. The cerebellum integrates this sensory and motor information as it carries out coordination and error checking during motor and perceptual functions. Hand-eye coordination is an example of cerebellar control; if the cerebellum is damaged, the eyes can follow a moving object, but they will not stop at the same place as the object. The cerebellum is also involved in learning and remembering motor skills. The embryonic diencephalon evolved into three adult brain regions: the thalamus, hypothalamus, and epithalamus. The embryonic diencephalon is the forebrain division that evolved earliest in vertebrate history. The thalamus and hypothalamus are major integrating centers that act as relay stations for information flow in the body. The epithalamus includes the pineal gland, the source of melatonin, and also contains one of several clusters of capillaries that generate cerebrospinal fluid from blood. The thalamus is the main input center for sensory information going to the cerebrum. Incoming information from all the senses is sorted in the thalamus and sent to the appropriate cerebral centers for further processing. The thalamus also receives input from the cerebrum and other parts of the brain that regulate emotion and arousal. The thalamus is formed by two masses, each roughly the size and shape of a walnut. The hypothalamus is one of the most important brain regions for the control of homeostasis. The hypothalamus contains the body’s thermostat as well as centers for regulating hunger, thirst, and other basic survival mechanisms. The hypothalamus is the source of posterior pituitary hormones and of releasing hormones that act on the anterior pituitary. Hypothalamic centers play a role in sexual and mating behaviors, the fight-or-flight response, and pleasure. The hypothalamus regulates the biological clock. Specialized nerve cells within the hypothalamus regulate circadian rhythms, daily cycles of biological activity. Organisms from bacteria and fungi to plants, insects, birds, and humans display these rhythms. In mammals, the cycles controlled by the hypothalamus influence a number of processes, including sleep, body temperature, hunger, and hormone release. Circadian rhythms in mammals rely on a biological clock, a molecular mechanism that directs periodic gene expression and cellular activity. Biological clocks can maintain a 24-hour cycle even in the absence of environmental cues. Humans kept in a constant environment exhibit a cycle length of 24.2 hours, with little variation. In mammals, circadian rhythms are coordinated by a pair of hypothalamic structures called the suprachiasmatic nucleus, or SCN. In response to visual information, the SCN acts as a pacemaker to synchronize the body’s biological clocks to the natural cycles of day length. Animals whose SCN are removed lack rhythmicity in behaviors and brain activity. In 1990, Michael Menaker transplanted brain tissue between normal and mutant hamsters with faulty circadian rhythms and demonstrated that the SCN determines the circadian rhythm of the whole animal. In mammals, information processing is largely centered in the cerebrum. The cerebrum develops from the embryonic telencephalon, an outgrowth of the forebrain that arose early in vertebrate evolution as a region supporting olfactory reception as well as auditory and visual processing. The cerebrum is divided into right and left cerebral hemispheres. Each hemisphere consists of an outer covering of gray matter, the cerebral cortex; internal white matter; and groups of neurons collectively called basal nuclei located deep within the white matter. The basal nuclei are important centers for planning and learning movement sequences. Damage in this brain region during fetal development can result in cerebral palsy, a defect that disrupts the issuance of motor commands to the muscles. The cerebral cortex is particularly extensive in mammals, where it is vital for perception, voluntary movement, and learning. In humans, the cerebral cortex accounts for about 80% of total brain mass and is highly convoluted. Due to its convolutions, the cerebral cortex has a large surface area but still fits inside the skull: Less than 5 mm thick, it has a surface area of approximately 1000 cm2. The cerebral cortex is divided into right and left sides, each responsible for the opposite half of the body. The left side of the cortex receives information from, and controls the movement of, the right side of the body, and vice versa. A thick band of axons known as the corpus callosum enables communication between the right and left cerebral cortices. The cerebrum is very plastic, especially early in development, and areas of the brain can take on novel functions. A dramatic example of this phenomenon results from a treatment for the most extreme cases of epilepsy, a condition causing episodes of electrical disturbance, or seizures, in the brain. Infants with severe epilepsy may have a cerebral hemisphere surgically removed. Amazingly, recovery is nearly complete, as the remaining hemisphere assumes most of the functions normally provided by the entire cerebrum. Even in adults, damage to a portion of the cerebral cortex can trigger the development or use of new brain circuits, leading in some cases to recovery of function. Some vertebrates demonstrate cognition. In humans, the outermost part of the cerebral cortex forms the neocortex, six parallel layers of neurons arranged tangential to the brain surface. Such a large, highly convoluted neocortex was thought to be required for advanced cognition, the perception and reasoning that form knowledge. Both primates and cetaceans possess an extensively convoluted neocortex. Birds lack a neocortex and were thought to have substantially lower intellectual capacity. In fact, birds are capable of sophisticated information processing. Scrub jays can remember the relative period of time that has passed since they stored and hid specific food items. New Caledonian crows are highly skilled at making and using tools, an ability otherwise well documented for only humans and great apes. African gray parrots understand relational concepts that are numerical or abstract, distinguishing between “same” and “different” and grasping the concept of “none.” The sophisticated cognitive ability of birds is based on an evolutionary variation on the architecture of the pallium, the top or outer portion of the brain. Whereas the human pallium—the cerebral cortex—contains flat sheets of cells in six layers, the avian pallium contains neurons clustered into nuclei. This organization, likely ancestral in vertebrates, was transformed into a layered one early in mammalian evolution. Connectivity was maintained during this transformation so that, for example, the pallium of both mammals and birds receives sensory input—sights, sounds, and touch—from the thalamus. The result was two different arrangements, each supporting complex and flexible brain function. Concept 49.3 The cerebral cortex controls voluntary movement and cognitive functions. Each side of the cerebral cortex is made up of the frontal, temporal, occipital, and parietal lobes (each named for a bone of the skull). Each lobe contains a number of functional areas, including primary sensory areas, which receive and process a specific type of sensory information, and association areas, which integrate the information from various parts of the brain. The increased size of the cerebral cortex during mammalian evolution resulted from an expansion of the association areas. A rat’s cerebral cortex contains mainly primary sensory areas, whereas a human cerebral cortex consists largely of association areas responsible for more complex behavior and learning. The cerebral cortex processes information. The cerebral cortex receives sensory input from dedicated sensory organs, such as the eyes and nose, as well as receptors in the hands, scalp, and elsewhere. Somatosensory receptors provide information about touch, pain, pressure, temperature, and the position of muscles and limbs. Sensory information coming into the cortex is directed via the thalamus to primary sensory areas within the brain lobes. Different types of input are directed to distinct locations: visual information to the occipital lobe, auditory input to the temporal lobe, and somatosensory information to the parietal lobe. Information about taste goes to the parietal lobe, but to a region separate from the area for somatosensory input. Olfactory information is first sent to regions of the cortex that are similar in mammals and reptiles and then via the thalamus to an interior part of the frontal lobe. Information received at the primary sensory areas is passed to association areas, which process particular features in the sensory input. In the occipital lobe, some groups of neurons in the primary visual area are specifically sensitive to rays of light oriented in a particular direction. In the visual association area, information related to such features is combined in a region dedicated to recognizing complex images, such as faces. Integrated sensory information is passed to the frontal association area, which helps plan actions and movement. The cerebral cortex then generates motor commands that cause particular behaviors. These commands consist of action potentials produced by neurons in the motor cortex, which lies at the rear of the frontal lobe. The action potentials travel along axons to the brain stem and spinal cord, where they excite motor neurons, which in turn excite skeletal muscle cells. In both the somatosensory cortex and the motor cortex, neurons are distributed in an orderly fashion according to the part of the body that generates the sensory input or receives the motor commands. Neurons that process sensory information from the legs and feet are located in the region of the somatosensory cortex that lies closest to the midline. Neurons that control muscles in the legs and feet are located in the corresponding region of the motor cortex. The cortical surface area devoted to each body part is not proportional to the size of the part. Instead, the surface area correlates with the extent of neuronal control needed for muscles in a particular body part (for the motor cortex) or with the number of sensory neurons that extend axons to that part (for the somatosensory cortex). For example, the surface area of the motor cortex devoted to the face is very large, reflecting the extensive involvement of facial muscles. Language and speech are localized in the brain. Damage to particular regions of the cortex by injuries, strokes, or tumors can produce distinctive changes in a person’s behavior. French physician Pierre Broca conducted postmortems on patients who could understand language but could not speak and found that many of them had defects in a small region of the left frontal lobe. That region, known as Broca’s area, is in front of the part of the primary motor cortex that controls muscles in the face. The German physician Karl Wernicke found that damage to a posterior portion of the left temporal lobe, now called Wernicke’s area, abolished the ability to comprehend speech but not the ability to speak. More than a century later, studies of brain activity using fMRI and positron-emission tomography have confirmed that Broca’s area is active during the generation of speech and Wernicke’s area is active when speech is heard. Broca’s area and Wernicke’s area are part of a much larger network of brain regions involved in language. Reading a printed word without speaking activates the visual cortex; reading a printed word aloud activates both the visual cortex and Broca’s area. Frontal and temporal areas become active when meaning must be attached to words, such as when a person generates verbs to go with nouns or groups related words or concepts. Cortical function is lateralized. The two human cerebral hemispheres do not have identical functions. The left side of the cerebrum plays a dominant role with regard to language, as reflected in the location of both Broca’s area and Wernicke’s area in the left hemisphere. The left hemisphere is more adept at math and logical operations, while the right hemisphere is dominant in the recognition of faces and patterns, spatial relations, and nonverbal thinking. These differences in hemisphere function in humans are termed lateralization. Some lateralization relates to handedness, the preference for using one hand for certain motor activities. Roughly 90% of individuals in all human populations are right-handed. fMRI studies have revealed that language processing differs in relation to handedness. When subjects thought of words without speaking out loud, brain activity was localized to the left hemisphere in 96% of right-handed subjects but in only 76% of left-handed subjects. The two hemispheres normally work together, exchanging information through the fibers of the corpus callosum. Patients with extreme forms of epilepsy who have their corpus callosum surgically severed exhibit a “split-brain” effect. When they see a familiar word in their left field of vision, they cannot read the word: The sensory information that travels from the left field of vision to the right hemisphere cannot reach the language centers in the left hemisphere. Each hemisphere in such patients functions independently of the other. The generation and experience of emotions involve many regions of the brain. The limbic system, which includes the amygdala, the hippocampus, and parts of the thalamus, is a group of structures surrounding the brain stem in mammals. Structures within the limbic system have diverse functions, including emotion as well as motivation, olfaction, behavior, and memory. Parts of the brain outside the limbic system also play a role in the generation and experience of emotion. Emotions that manifest themselves in behaviors such as laughing and crying involve an interaction of parts of the limbic system with sensory areas of the cerebrum. Structures in the forebrain attach emotional “feelings” to basic, survival-related functions controlled by the brain stem, including aggression, feeding, and sexuality. Emotional experiences may be stored separately from the system that supports explicit recall of events. The focus of emotional memory is the amygdala, which is located in the temporal lobe. Adults who learn to avoid an aversive situation, such as an image that is always followed by a mild electrical shock, remember the image and undergo autonomic arousal—as measured by increased heart rate or sweating—when they see the image again. People with brain damage confined to the amygdala do not exhibit autonomic arousal but can recall the image because explicit memory is intact. The prefrontal cortex, a part of the frontal lobes critical for emotional experience, is also important in temperament and decision making. In a famous 19th-century case, Phineas Gage was injured by a meter-long rod that penetrated into his frontal lobe. Gage recovered, but his personality changed drastically. He became emotionally detached, impatient, and erratic in his behavior. Tumors that develop in the frontal lobe sometimes cause the same combination of symptoms that Gage experienced. Intellect and memory seem intact, but decision making is flawed and emotional responses are diminished. In the 20th century, the same problems were observed as a consequence of frontal lobotomy, a discredited surgical procedure that severs the connection between the prefrontal cortex and the limbic system. Behavioral disorders are now treated instead with drug therapy. Consciousness is an emergent property of the brain. Over the past few decades, neuroscientists have studied consciousness using brain-imaging techniques such as fMRI and PET scans. Neuroscientists can compare activity in the human brain during different states of consciousness (for example, before and after a person is aware of seeing an object). Imaging techniques can also be used to compare the conscious and unconscious processing of sensory information, providing an increasingly detailed picture of how neural activity correlates with conscious experiences. There is a growing consensus among neuroscientists that consciousness is an emergent property of the brain, one that recruits activities in many areas of the cerebral cortex. Several models postulate the existence of a sort of “scanning mechanism” that repetitively sweeps across the brain, integrating widespread activity into a unified, conscious moment. Concept 49.4 Changes in synaptic connections underlie memory and learning. During embryonic development, regulated gene expression and signal transduction establish the overall structure of the nervous system. Two processes dominate the remaining development of the nervous system. In the first process, neurons compete for growth factors, which are produced in limiting quantities by target tissues. Cells that don't reach their targets fail to receive factors and undergo programmed cell death. In fact, half of the neurons formed in the embryo are eliminated. The second process is synapse elimination. A developing neuron forms many synapses, more than it needs. The activity of the neuron stabilizes some synapses and destabilizes others. By the end of embryogenesis, most neurons have lost more than half of their initial synapses, leaving behind the connections that survive into adulthood. Together, neuron and synapse elimination set up the network of cells and connections within the nervous system required throughout life. Nervous systems are plastic and can be remodeled. Although the basic architecture of the CNS is established during embryonic development, it can change after birth. The capacity for the nervous system to be remodeled in response to its own activity is called neural plasticity. Much of the reshaping of the nervous system occurs at synapses. When the activity of a synapse correlates with the activity of other synapses, changes may occur that reinforce that synaptic connection. When the activity of a synapse fails to correlate with the activity of other synapses, the synaptic connection weakens. These processes can result in either loss or addition of a synapse. These changes result in increased signaling between particular pairs of neurons and decreased signaling at other sites. Changes can also strengthen or weaken signaling at a synapse. Remodeling and refinement of the nervous system occur in many contexts as we develop the ability to sense our surroundings or recover from injury or disease. Short- and long-term memories are organized differently in the brain. Some information is held in short-term memory locations and released as it becomes irrelevant. For knowledge that is retained longer, the mechanisms of long-term memory are activated. Information can be fetched from long-term memory and returned to short-term memory. Both types of memory are stored in the cerebral cortex. Short-term memories are accessed via temporary associations formed in the hippocampus. For long-term memories, the links in the hippocampus are replaced by more permanent connections within the cerebral cortex. The hippocampus is essential for acquiring new long-term memories, but not for maintaining them. People who suffer damage to the hippocampus cannot form any new lasting memories, but they can recall past events from before their injury. What evolutionary advantage is offered by different organizations for short-term and long-term memories? The delay in forming connections in the cerebral cortex enables long-term memories to be integrated into the existing store of knowledge and experience, allowing meaningful associations. Consistent with this idea, the transfer of information from short-term to long-term memory is enhanced by the association of new data with data previously learned and stored in long-term memory. Motor skills are usually learned by repetition. You can perform motor skills without consciously recalling the individual steps required to do these tasks correctly. The learning of skills and procedures involves cellular mechanisms very similar to those responsible for brain growth and development, as neurons actually make new connections. In contrast, the memorization of phone numbers, facts, and places—which can be very rapid and may require only one exposure to the relevant item—may rely mainly on changes in the strength of existing neural connections. Long-term potentiation (LTP) leads to a lasting increase in the strength of synaptic transmission. LTP, first characterized in tissue slices from the hippocampus, involves a presynaptic neuron that releases the excitatory neurotransmitter glutamate. For LTP to occur there must be a brief, high-frequency series of action potentials in this presynaptic neuron, which must arrive at the synaptic terminal at the same time the postsynaptic cell receives a depolarizing stimulus. LTP involves two types of glutamate receptors, each named for a molecule—NMDA or AMPA—that artificially activates that receptor. The set of receptors present on the postsynaptic membranes changes in response to an active synapse and a depolarizing stimulus. The result is long-term potentiation—a stable increase in the size of the postsynaptic potentials at the synapse. LTP is one of the fundamental processes by which memories are stored and learning takes place. Concept 49.5 Nervous system disorders can be understood in molecular terms. Disorders of the nervous system, including schizophrenia, depression, Alzheimer’s disease, and Parkinson’s disease, result in more hospitalizations in the United States than do heart disease or cancer. Many disorders that alter mood or behavior can now be treated with drugs. Societal attitudes are changing as awareness grows that nervous system disorders result from chemical or anatomical changes in the brain. Major research efforts are under way to identify genes that cause or contribute to disorders of the nervous system. Identifying such genes offers hope for identifying causes, predicting outcomes, and developing effective treatments. Genetic contributions only partially account for most of these disorders, however. The other significant contribution comes from environmental factors. To distinguish between genetic and environmental variables, scientists often carry out family studies, tracking how family members are related, which individuals are affected, and which family members grew up in the same household. These studies are especially informative when one of the affected individuals has a genetically identical twin or an adopted sibling who is genetically unrelated. Schizophrenia has a very strong genetic component. About 1% of the world’s population suffers from schizophrenia, a severe mental disturbance characterized by psychotic episodes in which patients lose the ability to distinguish reality. Schizophrenics typically suffer from hallucinations (such as “voices” that only they can hear) and delusions (for example, the idea that others are plotting to harm them). Schizophrenics suffer fragmentation of normally integrated brain functions. Two lines of evidence suggest that schizophrenia affects neuronal pathways that use dopamine as a neurotransmitter. Amphetamine, which stimulates dopamine release, can produce the same symptoms as schizophrenia. Many of the drugs that alleviate the symptoms of schizophrenia block dopamine receptors. Schizophrenia may also alter glutamate signaling because the street drug “angel dust” or PCP blocks glutamate receptors and induces strong schizophrenia-like symptoms. New medications are relatively safe and can alleviate the major symptoms of schizophrenia. Depression is a disorder characterized by depressed mood and abnormalities in sleep, appetite, and energy level. Individuals affected by major depressive disorder experience periods lasting weeks during which they have no interest in and take no pleasure from nearly any activity. One of the most common nervous system disorders, major depression affects about one in every seven adults at some point. Women are affected twice as often as men. Bipolar disorder involves swings of mood from high to low and affects about 1% of the world’s population. The manic phase is characterized by high self-esteem, increased energy, a flow of ideas, over-talkativeness, and increased risk taking. The depressive phase comes with lowered ability to feel pleasure, loss of motivation, sleep disturbances, and feelings of worthlessness, sometimes leading to suicide. Both bipolar disorder and major depression have genetic and environmental components. Major depressive and bipolar disorders are among the nervous system disorders for which available therapies are most effective. Many drugs, including Prozac, that are used to treat depressive illness increase the activity of biogenic amines in the brain. Depressive disorders are also sometimes treated with anticonvulsant drugs or lithium. Drug addiction is associated with the brain reward system. Drug addiction is a disorder characterized by compulsive consumption and a loss of control in limiting intake. A number of drugs that vary considerably in their effects on the CNS can be addictive. For example, cocaine and amphetamine act as stimulants, whereas heroin is a pain-relieving sedative. All of these drugs, as well as alcohol and tobacco, are addictive for the same reason: Each increases the activity of the brain’s reward system, neural circuitry that normally functions in pleasure, incentive motivation, and learning. In the absence of drug addiction, the reward system provides motivation for activities that enhance survival and reproduction, such as eating in response to hunger, drinking when thirsty, and engaging in sexual activity when aroused. In addicted individuals, motivation is directed toward drug consumption. Scientists have learned how the brain's reward system works and how particular drugs affect its function, largely through the use of experimental animals. Rats provide themselves with cocaine, heroin, or amphetamine when given a dispensing system linked to a lever in their cage. Rats may exhibit addictive behavior, continuing to self-administer the drug rather than seek food, even to the point of starvation. These and other studies have led to the identification of both the organization of the reward system and its key neurotransmitter, dopamine. Neural inputs are received by neurons in a region near the base of the brain called the ventral tegmental area (VTA). When activated, these neurons direct action potentials along axons that synapse with neurons in specific regions of the cerebrum and release dopamine. Addictive drugs affect the reward system. Each drug has an immediate effect that enhances the activity of the dopamine pathway. As addiction develops, long-lasting changes in the reward circuitry produce a craving for the drug, independent of any pleasure associated with consumption or distress associated with abstinence. Alzheimer’s disease is progressive and age related. Alzheimer’s disease is a dementia characterized by confusion and memory loss. Its incidence is age related, rising from about 10% at age 65 to about 35% at age 85. The disease is progressive, as patients become less able to function over time. There are also personality changes, almost always for the worse. Patients often lose their ability to recognize people, including family. Alzheimer’s disease involves the death of neurons in many areas of the brain, including the hippocampus and cerebral cortex, leading to massive shrinkage of brain tissue. Many symptoms of Alzheimer’s disease are shared with other forms of dementia, and the disease is difficult to diagnose while the patient is alive. A postmortem finding of two features—amyloid plaques and neurofibrillary tangles—in remaining brain tissue confirms a diagnosis of Alzheimer’s disease. The plaques are aggregates of -amyloid, an insoluble peptide cleaved from a membrane protein found in neurons. Membrane enzymes, called secretases, catalyze the cleavage, causing -amyloid to accumulate in plaques outside the neurons. It is these plaques that appear to trigger the death of surrounding neurons. The neurofibrillary tangles observed in persons with Alzheimer's disease mainly consist of the protein tau. Tau normally helps regulate the movement of nutrients along microtubules in neurons. In persons with Alzheimer’s disease, tau undergoes changes that cause it to bind to itself, resulting in neurofibrillary tangles. Parkinson’s disease is a motor disorder. Parkinson’s disease is characterized by difficulty in initiating movements, slowness of movement, and rigidity. Patients have muscle tremors, poor balance, a flexed posture, and a shuffling gait. Rigidity of the facial muscles decreases the ability to vary facial expressions. Parkinson’s disease is an age-related, progressive brain illness. The incidence of Parkinson’s disease is about 1% at age 65 and about 5% at age 85. In the U.S. population, approximately 1 million people are afflicted. The symptoms of Parkinson’s disease result from the death of neurons in the midbrain that normally release dopamine at synapses in the basal nuclei. As with Alzheimer’s disease, there is an accumulation of protein aggregates. A rare form of the disease that appears in relatively young adults has a clear genetic basis. Molecular studies of mutations linked to this early-onset Parkinson’s disease reveal the disruption of genes required for certain mitochondrial functions. Whether mitochondrial defects contribute to the more frequent form of the disease in older patients is a subject of active research. At present, there is no cure for Parkinson’s disease. Symptoms may be managed by brain surgery, deep-brain stimulation, and drugs such as L-dopa, a molecule that can cross the blood-brain barrier and be converted to dopamine within the CNS. One potential cure is to implant dopamine-secreting neurons, either in the midbrain or in the basal nuclei. Studies with animals make this a promising strategy: In rats with an experimentally induced condition that mimics Parkinson’s disease, transplantation of dopamine-secreting neurons can lead to a recovery of motor control. Neural stem cells may offer a cure for damaged or diseased brain tissue. Unlike the PNS, the mammalian CNS cannot fully repair itself when damaged or diseased. Surviving neurons in the brain can make new connections and sometimes compensate for damage, as in the remarkable recoveries of some stroke victims. Most brain and spinal cord injuries, strokes, and disorders that destroy CNS neurons, such as Alzheimer’s disease and Parkinson’s disease, have devastating and irreversible effects. In 1998, Fred Gage, at the Salk Institute in California, and Peter Ericksson, at the Sahlgrenska University Hospital in Sweden, announced that the adult human brain can produce new neurons. The evidence that new neurons form in the brains of adults came from a group of terminally ill cancer patients who had agreed to donate their brains for research upon their death. To monitor tumor growth in this group, doctors had given these patients bromodeoxyuridine (BrdU), an altered nucleotide that is incorporated into DNA during replication. DNA containing BrdU can be readily detected and thus marks cells that grow and divide after BrdU enters the body. Gage and Ericksson reasoned that BrdU would mark not only the growing tumor but also any cells in the brain that had recently divided. When the patients were examined postmortem, there was evidence of newly divided neurons in the hippocampus of each brain. The discovery of dividing neurons in the adult brain indicated the presence of stem cells, which retain the ability to divide indefinitely. Although some progeny of stem cells remain undifferentiated, others differentiate into specialized cells. In the brain, the stem cells are called neural progenitor cells and are committed to becoming either neurons or glia. One of the goals of further research is to find a way to induce the body’s own neural progenitor cells to differentiate into specific types of neurons or glia when and where they are needed. Another objective is to transplant cultured neural progenitor cells into a damaged CNS and have them restore function. Lecture Outline for Campbell/Reece Biology, 8th Edition, © Education, Inc. 49-1