Chapter 48   Nervous Systems
Lecture Outline
Overview: Command and Control Center

• The human brain contains an estimated 1011 (100 billion) neurons.
• Each neuron may communicate with thousands of other neurons in complex information-processing circuits.
• Recently developed technologies can record brain activity from outside the skull.
• One technique is functional magnetic resonance imaging (fMRI), which reconstructs a 3-D map of the subject’s brain activity.
• The results of brain imaging and other research methods show that groups of neurons function in specialized circuits dedicated to different tasks.

 The ability of cells to respond to the environment has evolved over billions of years.

• 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.
• Such cells could locate food sources by chemotaxis.
• Later, modification of this simple process provided multicellular organisms with a mechanism for communication between cells of the body.
• By the time of the Cambrian explosion, systems of neurons that allowed animals to sense and move rapidly had evolved in essentially modern form.
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• Concept 48.1 Nervous systems consist of circuits of neurons and supporting cells

 Nervous systems show diverse patterns of organization.

• All animals except sponges have some type of nervous system.
• What distinguishes nervous systems of different animal groups is how the neurons are organized into circuits.
• Cnidarians have radially symmetrical bodies organized around a gastrovascular cavity.
• In hydras, neurons controlling the contraction and expansion of the gastrovascular cavity are arranged in diffuse nerve nets.
• The nervous systems of more complex animals contain nerve nets, as well as nerves, which are bundles of fiberlike extensions of neurons.
• With cephalization come more complex nervous systems.
• Neurons are clustered in a brain near the anterior end in animals with elongated, bilaterally symmetrical bodies.
• In simple cephalized animals such as the planarian, a small brain and longitudinal nerve cords form a simple central nervous system (CNS).
• In more complex invertebrates, such as annelids and arthropods, behavior is regulated by more complicated brains and ventral nerve cords containing segmentally arranged clusters of neurons called ganglia.
• Nerves that connect the CNS with the rest of the animal’s body make up the peripheral nervous system (PNS).
• The nervous systems of molluscs correlate with lifestyle.
• Clams and chitons have little or no cephalization and simple sense organs.
• Squids and octopuses have the most sophisticated nervous systems of any invertebrates, rivaling those of some vertebrates.
• The large brain and image-forming eyes of cephalopods support an active, predatory lifestyle.

 Nervous systems consist of circuits of neurons and supporting cells.

• In general, there are three stages in the processing of information by nervous systems: sensory input, integration, and motor output.
• Sensory neurons transmit information from sensors that detect external stimuli (light, heat, touch) and internal conditions (blood pressure, muscle tension).
• Sensory input is conveyed to the CNS, where interneurons integrate the sensory input.
• Motor output leaves the CNS via motor neurons, which communicate with effector cells (muscle or endocrine cells).
• Effector cells carry out the body’s response to a stimulus.
• The stages of sensory input, integration, and motor output are easy to study in the simple nerve circuits that produce reflexes, the body’s automatic responses to stimuli.

 Networks of neurons with intricate connections form nervous systems.

• The neuron is the structural and functional unit of the nervous system.
• The neuron’s nucleus is located in the cell body.
• Arising from the cell body are two types of extensions: numerous dendrites and a single axon.
• Dendrites are highly branched extensions that receive signals from other neurons.
• An axon is a longer extension that transmits signals to neurons or effector cells.
• The axon joins the cell body at the axon hillock, where signals that travel down the axon are generated.
• Many axons are enclosed in a myelin sheath.
• Near its end, axons divide into several branches, each of which ends in a synaptic terminal.
• The site of communication between a synaptic terminal and another cell is called a synapse.
• At most synapses, information is passed from the transmitting neuron (the presynaptic cell) to the receiving cell (the postsynaptic cell) by means of chemical messengers called neurotransmitters.
• Glia are supporting cells that are essential for the structural integrity of the nervous system and for the normal functioning of neurons.
• There are several types of glia in the brain and spinal cord.
• Astrocytes are found within the CNS.
• They provide structural support for neurons and regulate the extracellular concentrations of ions and neurotransmitters.
• Some astrocytes respond to activity in neighboring neurons by facilitating information transfer at those neuron’s synapses.
• By inducing the formation of tight junctions between capillary cells, astrocytes help form the blood-brain barrier, which restricts the passage of substances into the CNS.
• In an embryo, radial glia form tracks along which newly formed neurons migrate from the neural tube.
• Both radial glia and astrocytes can also act as stem cells, generating neurons and other glia.
• Oligodendrocytes (in the CNS) and Schwann cells (in the PNS) are glia that form myelin sheaths around the axons of vertebrate neurons.
• These sheaths provide electrical insulation of the axon.
• In multiple sclerosis, myelin sheaths gradually deteriorate, resulting in a progressive loss of body function due to the disruption of nerve signal transmission.

Concept 48.2 Ion pumps and ion channels maintain the resting potential of a neuron
Every cell has a voltage, or membrane potential, across its plasma membrane.

• All cells have an electrical potential difference (voltage) across their plasma membrane).
• This voltage is called the membrane potential.
• In neurons, the membrane potential is typically between −60 and −80 mV when the cell is not transmitting signals.
• The membrane potential of a neuron that is not transmitting signals is called the resting potential.
• In all neurons, the resting potential depends on the ionic gradients that exist across the plasma membrane.
• In mammals, the extracellular fluid has a Na+ concentration of 150 millimolar (mM) and a K+ of 5 mM.
• In the cytosol, Na+ concentration is 15 mM, and K+ concentration is 150 mM.
• These gradients are maintained by the sodium-potassium pump.
• The magnitude of the membrane voltage at equilibrium, called the equilibrium potential (Eion), is given by a formula called the Nernst equation.
• For an ion with a net charge of +1, the Nernst equation is:
• Eion = 62mV (log [ion]outside/[ion]inside)
• The Nernst equation applies to any membrane that is permeable to a single type of ion.
• In our model, the membrane is only permeable to K+, and the Nernst equation can be used to calculate EK, the equilibrium potential for K+.
• With this K+ concentration gradient, K+ is at equilibrium when the inside of the membrane is 92 mV more negative than the outside.
• Assume that the membrane is only permeable to Na+.
• ENa, the equilibrium potential for Na+, is +62 mV, indicating that, with this Na+ concentration gradient, Na+ is at equilibrium when the inside of the membrane is 62 mV more positive than the outside.
• How does a real mammalian neuron differ from these model neurons?
• The plasma membrane of a real neuron at rest has many open potassium channels, but it also has a relatively small number of open sodium channels.
• Consequently, the resting potential is around −60 to −80 mV, between EK and ENa.
• Neither K+ nor Na + is at equilibrium, and there is a net flow of each ion (a current) across the membrane at rest.
• The resting membrane potential remains steady, which means that the K+ and Na+ currents are equal and opposite.
• The reason the resting potential is closer to EK than to ENa is that the membrane is more permeable to K+ than to Na+.
• If something causes the membrane’s permeability to Na+ to increase, the membrane potential will move toward ENa and away from EK.
• This is the basis of nearly all electrical signals in the nervous system.
• The membrane potential can change from its resting value when the membrane’s permeability to particular ions changes.
• Sodium and potassium play major roles, but there are also important roles for chloride and calcium ions.
• The resting potential results from the diffusion of K+ and Na+ through ion channels that are always open.
• These channels are ungated.
• Neurons also have gated ion channels, which open or close in response to one of three types of stimuli.
• Stretch-gated ion channels are found in cells that sense stretch, and open when the membrane is mechanically deformed.
• Ligand-gated ion channels are found at synapses and open or close when a specific chemical, such as a neurotransmitter, binds to the channel.
• Voltage-gated ion channels are found in axons (and in the dendrites and cell bodies of some neurons, as well as in some other types of cells) and open or close in response to a change in membrane potential.
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• Concept 48.3 Action potentials are the signals conducted by axons
• Gated ion channels are responsible for generating the signals of the nervous system.
• If a cell has gated ion channels, its membrane potential may change in response to stimuli that open or close those channels.
• Some stimuli trigger a hyperpolarization, an increase in the magnitude of the membrane potential.
• Gated K+ channels open, K+ diffuses out of the cell, and the inside of the membrane becomes more negative.
• Other stimuli trigger a depolarization, a reduction in the magnitude of the membrane potential.
• Gated Na+ channels open, Na+ diffuses into the cell, and the inside of the membrane becomes less negative.
• These changes in membrane potential are called graded potentials because the magnitude of the change—either hyperpolarization or depolarization—varies with the strength of the stimulus.
• A larger stimulus causes a larger change in membrane permeability and, thus, a larger change in membrane potential.
• In most neurons, depolarizations are graded only up to a certain membrane voltage, called the threshold.
• A stimulus strong enough to produce a depolarization that reaches the threshold triggers a different type of response, called an action potential.
• An action potential is an all-or-none phenomenon.
• Once triggered, it has a magnitude that is independent of the strength of the triggering stimulus.
• Action potentials of neurons are very brief—only 1–2 milliseconds in duration.
• This allows a neuron to produce them at high frequency.
• Both voltage-gated Na+ channels and voltage-gated K+ channels are involved in the production of an action potential.
• Both types of channels are opened by depolarizing the membrane, but they respond independently and sequentially: Na+ channels open before K+ channels.
• Each voltage-gated Na+ channel has two gates, an activation gate and an inactivation gate, and both must be open for Na+ to diffuse through the channel.
• At the resting potential, the activation gate is closed and the inactivation gate is open on most Na+ channels.
• Depolarization of the membrane rapidly opens the activation gate and slowly closes the inactivation gate.
• Each voltage-gated K+ channel has just one gate, an activation gate.
• At the resting potential, the activation gate on most K+ channels is closed.
• Depolarization of the membrane slowly opens the K+ channel’s activation gate.
• How do these channel properties contribute to the production of an action potential?
• When a stimulus depolarizes the membrane, the activation gates on some Na+ channels open, allowing more Na+ to diffuse into the cell.
• The Na+ influx causes further depolarization, which opens the activation gates on still more Na+ channels, and so on.
• Once the threshold is crossed, this positive-feedback cycle rapidly brings the membrane potential close to ENa during the rising phase.
• However, two events prevent the membrane potential from actually reaching ENa.
• The inactivation gates on most Na+ channels close, halting Na+ influx.
• The activation gates on most K+ channels open, causing a rapid efflux of K+.
• Both events quickly bring the membrane potential back toward EK during the falling phase.
• In fact, in the final phase of an action potential, called the undershoot, the membrane’s permeability to K+ is higher than at rest, so the membrane potential is closer to EK than it is at the resting potential.
• The K+ channels’ activation gates eventually close, and the membrane potential returns to the resting potential.
• The Na+ channels’ inactivation gates remain closed during the falling phase and the early part of the undershoot.
• As a result, if a second depolarizing stimulus occurs during this refractory period, it will be unable to trigger an action potential.

 Nerve impulses propagate themselves along an axon.

• The action potential is repeatedly regenerated along the length of the axon.
• An action potential achieved at one region of the membrane is sufficient to depolarize a neighboring region above the threshold level, thus triggering a new action potential.
• Immediately behind the traveling zone of depolarization due to Na+ influx is a zone of repolarization due to K+ efflux.
• In the repolarized zone, the activation gates of Na+ channels are still closed.
• Consequently, the inward current that depolarizes the axon membrane ahead of the action potential cannot produce another action potential behind it.
• Once an action potential starts, it normally moves in only one direction—toward the synaptic terminals.
• Several factors affect the speed at which action potentials are conducted along an axon.
• One factor is the diameter of the axon: the larger the axon’s diameter, the faster the conduction.
• In the myelinated neurons of vertebrates, voltage-gated Na+ and K+ channels are concentrated at gaps in the myelin sheath called nodes of Ranvier.
• Only these unmyelinated regions of the axon depolarize.
• Thus, the impulse moves faster than in unmyelinated neurons.
• This mechanism is called saltatory conduction.

Concept 48.4 Neurons communicate with other cells at synapses

• When an action potential reaches the terminal of the axon, it generally stops there.
• However, information is transmitted from a neuron to another cell at the synapse.
• Some synapses, called electrical synapses, contain gap junctions that do allow electrical current to flow directly from cell to cell.
• Action potentials travel directly from the presynaptic to the postsynaptic cell.
• In both vertebrates and invertebrates, electrical synapses synchronize the activity of neurons responsible for rapid, stereotypical behaviors.
• The vast majority of synapses are chemical synapses, which involve the release of chemical neurotransmitter by the presynaptic neuron.
• The presynaptic neuron synthesizes the neurotransmitter and packages it in synaptic vesicles, which are stored in the neuron’s synaptic terminals.
• When an action potential reaches a terminal, it depolarizes the terminal membrane, opening voltage-gated calcium channels in the membrane.
• Calcium ions (Ca2+) then diffuse into the terminal, and the rise in Ca2+ concentration in the terminal causes some of the synaptic vesicles to fuse with the terminal membrane, releasing the neurotransmitter by exocytosis.
• The neurotransmitter diffuses across the narrow gap, called the synaptic cleft, which separates the presynaptic neuron from the postsynaptic cell.
• The effect of the neurotransmitter on the postsynaptic cell may be direct or indirect.
• Information transfer at the synapse can be modified in response to environmental conditions.
• Such modification may form the basis for learning or memory.

 Neural integration occurs at the cellular level.

• At many chemical synapses, ligand-gated ion channels capable of binding to the neurotransmitter are clustered in the membrane of the postsynaptic cell, directly opposite the synaptic terminal.
• Binding of the neurotransmitter to the receptor opens the channel and allows specific ions to diffuse across the postsynaptic membrane.
• This mechanism of information transfer is called direct synaptic transmission.
• The result is generally a postsynaptic potential, a change in the membrane potential of the postsynaptic cell.
• Excitatory postsynaptic potentials (EPSPs) depolarize the postsynaptic neuron.
• The binding of neurotransmitter to postsynaptic receptors opens gated channels that allow Na+ to diffuse into and K+ to diffuse out of the cell.
• Inhibitory postsynaptic potential (IPSP) hyperpolarizes the postsynaptic neuron.
• The binding of neurotransmitter to postsynaptic receptors open gated channels that allow K+ to diffuse out of the cell and/or Cl− to diffuse into the cell.
• Various mechanisms end the effect of neurotransmitters on postsynaptic cells.
• The neurotransmitter may simply diffuse out of the synaptic cleft.
• The neurotransmitter may be taken up by the presynaptic neuron through active transport and repackaged into synaptic vesicles.
• Glia actively take up the neurotransmitter at some synapses and metabolize it as fuel.
• The neurotransmitter acetylcholine is degraded by acetylcholinesterase, an enzyme in the synaptic cleft.
• Postsynaptic potentials are graded; their magnitude varies with a number of factors, including the amount of neurotransmitter released by the presynaptic neuron.
• Postsynaptic potentials do not regenerate but diminish with distance from the synapse.
• Most synapses on a neuron are located on its dendrites or cell body, whereas action potentials are generally initiated at the axon hillock.
• Therefore, a single EPSP is usually too small to trigger an action potential in a postsynaptic neuron.
• Graded potentials (EPSPs and IPSPs) are summed to either depolarize or hyperpolarize a postsynaptic neuron.
• Two EPSPs produced in rapid succession at the same synapse can be added in an effect called temporal summation.
• Two EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron can be added, in an effect called spatial summation.
• Summation also applies to IPSPs.
• This interplay between multiple excitatory and inhibitory inputs is the essence of integration in the nervous system.
• The axon hillock is the neuron’s integrating center, where the membrane potential at any instant represents the summed effect of all EPSPs and IPSPs.
• Whenever the membrane potential at the axon hillock reaches the threshold, an action potential is generated and travels along the axon to its synaptic terminals.
• In indirect synaptic transmission, a neurotransmitter binds to a receptor that is not part of an ion channel.
• This binding activates a signal transduction pathway involving a second messenger in the postsynaptic cell.
• This form of transmission has a slower onset, but its effects have a longer duration.
• cAMP acts as a secondary messenger in indirect synaptic transmission.
• When the neurotransmitter norepinephrine binds to its receptor, the neurotransmitter-receptor complex activates a G-protein, which in turn activates adenylyl cyclase, the enzyme that converts ATP to cAMP.
• cAMP activates protein kinase A, which phosphorylates specific channel proteins in the postsynaptic membrane, causing them to open or close.
• Because of the amplifying effect of the signal transduction pathway, the binding of a neurotransmitter to a single receptor can open or close many channels.

 The same neurotransmitter can produce different effects on different types of cells.

• Each of the known neurotransmitters binds to a specific group of receptors.
• Some neurotransmitters have a dozen or more receptors, which can produce very different effects in postsynaptic cells.
• Acetylcholine is one of the most common neurotransmitters in both invertebrates and vertebrates.
• In the vertebrate CNS, it can be inhibitory or excitatory, depending on the type of receptor.
• At the vertebrate neuromuscular junction, acetylcholine released by the motor neuron binds to receptors on ligand-gated channels in the muscle cell, producing an EPSP via direct synaptic transmission.
• Nicotine binds to the same receptors.
• Acetylcholine is inhibitory to cardiac muscle cell contraction.
• Biogenic amines are neurotransmitters derived from amino acids.
• One group, known as catecholamines, consists of neurotransmitters produced from the amino acid tyrosine.
• This group includes epinephrine and norepinephrine and a closely related compound called dopamine.
• Another biogenic amine, serotonin, is synthesized from the amino acid tryptophan.
• The biogenic amines are usually involved in indirect synaptic transmission, most commonly in the CNS.
• Dopamine and serotonin affect sleep, mood, attention, and learning.
• Imbalances in these neurotransmitters are associated with several disorders.
• Parkinson’s disease is associated with a lack of dopamine in the brain.
• LSD and mescaline produce hallucinations by binding to brain receptors for serotonin and dopamine.
• Depression is treated with drugs that increase the brain concentrations of biogenic amines such as norepinephrine and serotonin.
• Prozac inhibits the uptake of serotonin after its release, increasing its effect.
• Four amino acids function as neurotransmitters in the CNS: gamma aminobutyric acid (GABA), glycine, glutamate, and aspartate.
• GABA is the neurotransmitter at most inhibitory synapses in the brain, where it produces IPSPs.
• Several neuropeptides, relatively short chains of amino acids, serve as neurotransmitters.
• Most neurons release one or more neuropeptides as well as a nonpeptide neurotransmitter.
• Neuropeptides usually operate via signal transduction pathways.
• The neuropeptide substance P is a key excitatory neurotransmitter that mediates our perception of pain.
• Other neuropeptides, endorphins, act as natural analgesics.
• Opiates such as morphine and heroin bind to receptors on brain neurons by mimicking endorphins, which are produced in the brain under times of physical or emotional stress.
• Some neurons of the vertebrate PNS and CNS release dissolved gases, especially nitric oxide and carbon monoxide, which act as local regulators.
• During male sexual arousal, certain neurons release NO into the erectile tissue of the penis.
• In response, smooth muscle cells in the blood vessel walls of the erectile tissue relax, allowing the blood vessels to dilate and fill the spongy erectile tissue with blood, producing an erection.
• Viagra inhibits an enzyme that slows the muscle-releasing effects of NO.
• Carbon monoxide is synthesized by the enzyme heme oxygenase.
• In the brain, CO regulates the release of hypothalamic hormones.
• In the PNS, it acts as an inhibitory neurotransmitter that hyperpolarizes intestinal smooth muscle cells.
• NO and CO are synthesized by cells as needed.
• They diffuse into neighboring target cells, produce an effect, and are broken down, all within a few seconds.

Concept 48.5 The vertebrate nervous system is regionally specialized
Vertebrate nervous systems have central and peripheral components.

• In all vertebrates, the nervous system shows a high degree of cephalization and has distinct CNS and PNS components.
• The brain provides integrative power that underlies the complex behavior of vertebrates.
• The spinal cord integrates simple responses to certain kinds of stimuli and conveys information to and from the brain.
• The vertebrate CNS is derived from the dorsal embryonic nerve cord, which is hollow.
• In the adult, this feature persists as the narrow central canal of the spinal cord and the four ventricles of the brain.
• Both the canal and the ventricles are filled with cerebrospinal fluid, which is formed in the brain by filtration of the blood.
• Cerebrospinal fluid circulates through the central canal and ventricles and then drains into the veins, assisting in the supply of nutrients and hormone and the removal of wastes.
• In mammals, the fluid cushions the brain and spinal cord by circulating between two of the meninges, layers of connective tissue that surround the CNS.
• White matter of the CNS is composed of bundles of myelinated axons.
• Gray matter consists of unmyelinated axons, nuclei, and dendrites.

 The divisions of the peripheral nervous system interact in maintaining homeostasis.

• The PNS transmits information to and from the CNS and plays an important role in regulating the movement and internal environment of a vertebrate.
• The vertebrate PNS consists of left-right pairs of cranial and spinal nerves and their associated ganglia.
• Paired cranial nerves originate in the brain and innervate the head and upper body.
• Paired spinal nerves originate in the spinal cord and innervate the entire body.
• The PNS can be divided into two functional components: the somatic nervous system and the autonomic nervous system.
• The somatic nervous system carries signals to and from skeletal muscle, mainly in response to external stimuli.
• It is subject to conscious control, but much skeletal muscle activity is actually controlled by reflexes mediated by the spinal cord or the brainstem.
• The autonomic nervous system regulates the internal environment by controlling smooth and cardiac muscles and the organs of the digestive, cardiovascular, excretory, and endocrine systems.
• Three divisions make up the autonomic nervous system: sympathetic, parasympathetic, and enteric.
• Activation of the sympathetic division correlates with arousal and energy generation—the “flight or fight” response.
• Activation of the parasympathetic division generally promotes calming and a return to self-maintenance functions—“rest and digest.”
• When sympathetic and parasympathetic neurons innervate the same organ, they often have antagonistic effects.
• The enteric division consists of complex networks of neurons in the digestive tract, pancreas, and gallbladder.
• The enteric networks control the secretions of these organs as well as activity in the smooth muscles that produce peristalsis.
• The sympathetic and parasympathetic divisions normally regulate the enteric division.
• The somatic and autonomic nervous systems often cooperate in maintaining homeostasis.

 Embryonic development of the vertebrate brain reflects its evolution from three anterior bulges of the neural tube.

• In all vertebrates, three bilaterally symmetrical, anterior bulges of the neural tube form the forebrain, midbrain, and hindbrain during embryonic development.
• Over vertebrate evolution, the brain became further divided structurally and functionally, providing additional complex integration.
• The forebrain is particularly enlarged in birds and mammals.
• Five brain regions form by the fifth week of human embryonic development.
• The telencephalon and diencephalon develop from the forebrain.
• The mesencephalon develops from the midbrain.
• The metencephalon and myelencephalon develop from the hindbrain.
• The telencephalon gives rise to the cerebrum.
• Rapid growth of the telencephalon during the second month of human development causes the outer portion of the cerebrum, the cerebral cortex, to extend over the rest of the brain.
• The adult brainstem consists of the midbrain (derived from the mesencephalon), the pons (derived from the metencephalon), and the medulla oblongata (derived from the myelencephalon).
• The metencephalon also gives rise to the cerebellum.

 Evolutionarily older structures of the vertebrate brain regulate essential automatic and integrative functions.

• The brainstem is one of the evolutionarily older parts of the brain.
• Sometimes called the “lower brain,” it consists of the medulla oblongata, pons, and midbrain.
• The brain stem functions in homeostasis, coordination of movement, and conduction of impulses to higher brain centers.
• Centers in the brainstem contain neuron cell bodies that send axons to many areas of the cerebral cortex and cerebellum, releasing neurotransmitters.
• Signals in these pathways cause changes in attention, alertness, appetite, and motivation.
• The medulla oblongata contains centers that control visceral (autonomic, homeostatic) functions, including breathing, heart and blood vessel activity, swallowing, vomiting, and digestion.
• The pons also participates in some of these activities.
• It regulates the breathing centers in the medulla.
• Information transmission to and from higher brain regions is one of the most important functions of the medulla and pons.
• The two regions also help coordinate large-scale body movements.
• Axons carrying instructions about movement from the midbrain and forebrain to the spinal cord cross from one side of the CNS to the other in the medulla.
• The right side of the brain controls the movement of the left side of the body, and vice versa.
• The midbrain contains centers involved in the receipt and integration of sensory information.
• Superior colliculi are involved in the regulation of visual reflexes.
• Inferior colliculi are involved in the regulation of auditory reflexes.
• The midbrain relays information to and from higher brain centers.
• The reticular activating system (RAS) of the reticular formation regulates sleep and arousal.
• Acting as a sensory filter, the RAS selects which information reaches the cerebral cortex.
• The more information the cortex receives, the more alert and aware the person is.
• The brain can ignore some stimuli while actively processing other input.
• Sleep and wakefulness are regulated by specific parts of the brainstem.
• The pons and medulla contain centers that cause sleep when stimulated, and the midbrain has a center that causes arousal.
• Serotonin may be the neurotransmitter of the sleep-producing centers.
• All birds and mammals show characteristic sleep/wake cycles.
• Melatonin, a hormone produced by the pineal gland, appears to play an important role in these cycles.
• The function of sleep is still not fully understood.
• One hypothesis is that sleep is involved in the consolidation of learning and memory, and experiments show that regions of the brain activated during a learning task can become active again during sleep.
• The cerebellum develops from part of the metencephalon.
• It functions to error-check and coordinate motor activities, and perceptual and cognitive functions.
• The cerebellum is involved in learning and remembering motor skills.
• It relays sensory information about joints, muscles, sight, and sound to the cerebrum.
• The cerebellum also coordinates motor commands issued by the cerebrum.
• The embryonic diencephalon develops into three adult brain regions: the epithalamus, thalamus, and hypothalamus.
• The epithalamus includes the pineal gland and the choroid plexus, one of several clusters of capillaries that produce cerebrospinal fluid from blood.
• The thalamus relays all sensory information to the cerebrum and relays motor information from 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.
• Although it weighs only a few grams, the hypothalamus is a crucial brain region for homeostatic regulation.
• It is the source of posterior pituitary hormones and releasing hormones that act on the anterior pituitary.
• The hypothalamus also contains centers involved in thermoregulation, hunger, thirst, sexual and mating behavior, and pleasure.
• Animals exhibit circadian rhythms, one being the sleep/wake cycle.
• The biological clock is an internal timekeeper that regulates a variety of physiological phenomena, including hormone release, hunger, and sensitivity to external stimuli.
• In mammals, the hypothalamic suprachiasmatic nuclei (SCN) function as a biological clock.
• The clock’s rhythm requires external cues to remain synchronized with environmental cycles.
• Experiments in which humans have been deprived of external cues have shown that the human biological clock has a period of 24 hours and 11 minutes.

 The cerebrum is the most highly developed structure of the mammalian brain.

• The cerebrum is derived from the embryonic telencephalon and is divided into left and right cerebral hemispheres.
• Each hemisphere consists of an outer covering of gray matter, the cerebral cortex; internal white matter; and groups of neurons deep within the white matter called basal nuclei.
• The basal nuclei are important centers for planning and learning movement sequences.
• In humans, the largest and most complex part of the brain is the cerebral cortex.
• It is here that sensory information is analyzed, motor commands are issued, and language is generated.
• The cerebral cortex underwent a dramatic expansion when the ancestors of mammals diverged from reptiles.
• Mammals have a region of the cerebral cortex known as the neocortex.
• The neocortex forms the outermost part of the mammalian cerebrum, consisting of six parallel layers of neurons running tangential to the brain surface.
• The human neocortex is highly convoluted, allowing the region to have a large surface area and still fit inside the skull.
• Although less than 5 mm thick, the human neocortex has a surface area of about 0.5m2 and accounts for about 80% of the total brain mass.
• Nonhuman primates and cetaceans also have exceptionally large, convoluted neocortices.
• The surface area relative to body size of a porpoise’s neocortex is second only to that of a human.
• The cerebral cortex is divided into right and left sides.
• The left hemisphere is primarily responsible for the right side of the body.
• The right hemisphere is primarily responsible for the left side of the body.
• A thick band of axons known as the corpus callosum is the major connection between the two hemispheres.
• Damage to one area of the cerebrum early in development can frequently cause redirection of its normal functions to other areas.

Concept 48.6 The cerebral cortex controls voluntary movement and cognitive functions

• The cerebrum is divided into frontal, temporal, occipital, and parietal lobes.
• Researchers have identified a number of functional areas within each lobe.
• These areas include primary sensory areas, each of which receives and processes a specific type of sensory information, and association areas, which integrate the information from various parts of the brain.
• The major increase in the size of the neocortex that occurred during mammalian evolution was mostly an expansion of the association areas that integrate higher cognitive functions and make more complex behavior and learning possible.
• Most sensory information coming into the cortex is directed via the thalamus to primary sensory areas within the lobes: visual information to the occipital lobe; auditory input to the temporal lobe; and somatosensory information about touch, pain, pressure, temperature, and position of limbs and muscles to the parietal lobe.
• In mammals, olfactory information is first sent to regions in the cortex that are similar in mammals and reptiles, and then via the thalamus to an interior part of the frontal lobe.
• Based on the integrated sensory information, the cerebral cortex can generate motor commands that cause specific behaviors.
• These commands consist of action potentials produced by neurons in the primary motor cortex, which lies at the rear of the frontal lobe.
• The action potentials travel along axons to the brainstem 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 command.
• The cortical surface area devoted to each body part is not related to the size of the part.
• Instead it is related to the number of sensory neurons that innervate that part (for the somatosensory cortex) or the amount of skill needed to control muscles in that part (for the motor cortex).
• During brain development, competing functions segregate and displace each other in the cortex of the left and right cerebral hemispheres, resulting in lateralization of brain function.
• The left hemisphere specializes in language, math, logic operations, and the processing of serial sequences of information, and fine visual and auditory details.
• It specializes in detailed activities required for motor control.
• The right hemisphere specializes in pattern recognition, spatial relationships, nonverbal ideation, emotional processing, and the parallel processing of information.
• Understanding and generating the stress and intonation patterns of speech that convey its emotional content is primarily a right-hemisphere function, as is musical appreciation.
• The right hemisphere specializes in perceiving the relationship between images and the whole context in which they occur, whereas the left hemisphere is better at focused perception.
• The two hemispheres work together, exchanging information through the fibers of the corpus callosum.
• Broca’s area, located in the left hemisphere’s frontal lobe, is responsible for speech production.
• Wernicke’s area, located in the right hemisphere’s temporal lobe, is responsible for speech comprehension.
• Studies of brain activity using fMRI and positron-emission tomography (PET) confirm that Broca’s area is active during the generation of speech, while Wernicke’s area is active when speech is heard.
• These areas are part of a larger network of brain regions involved in language, including the visual cortex (for reading) and frontal and temporal areas that are involved in generating verbs to match nouns and grouping together related words and concepts.
• Emotions are the result of a complex interplay of many regions of the brain.
• The limbic system is a ring of structures around the brainstem, including three parts of the cerebral cortex—the amygdala, hippocampus, and olfactory bulb—along with some inner portions of the cortex’s lobes, and parts of the thalamus and hypothalamus.
• These structures interact with sensory areas of the neocortex to mediate primary emotions that result in laughing or crying.
• It also attaches emotional “feelings” to basic, survival-level functions controlled by the brainstem, including aggression, feeding, and sexuality.
• The limbic system is central to crucial mammalian behaviors involved in emotional bonding and extended nurturing of infants.
• The amygdala, a structure in the temporal lobe, is central in recognizing the emotional content of facial expression and laying down emotional memories.
• This emotional memory system seems to appear earlier in development than the system that supports explicit recall of events, which requires the hippocampus.
• As children develop, primary emotions such as pleasure and fear are associated with different situations in a process that requires portions of the neocortex, especially the prefrontal cortex.
• Damage to regions of the frontal cortex may leave the patient’s intelligence and memories intact, but destroy their motivation, foresight, goal formation, and decision making.
• Frontal lobotomy was a widely performed surgical procedure in which the connection between the prefrontal cortex and the limbic system was disrupted.
• This technique was used to treat severe emotional problems.
• It resulted in docility and the loss of ability to concentrate, plan, and work toward goals.
• Drug therapy has replaced frontal lobotomy.
• Short-term memories are stored in the frontal lobes and released as they become irrelevant.
• Should we wish to retain knowledge of short-term memories, long-term memories are established by mechanisms involving the hippocampus.
• The transfer of information from short-term to long-term memory is enhanced by repetition (“practice makes perfect”), positive or negative emotional states mediated by the amygdala, and the association of the new data with previously stored information.
• Many sensory and motor association areas of the cerebral cortex outside Broca’s area and Wernicke’s area are involved in storing and retrieving words and images.
• The memorization of information can be very rapid and may rely mainly on rapid changes in the strength of existing neural connections.
• In contrast, the slow learning and remembering of skills and procedures appear to involve the formation of new connections between neurons, by cellular mechanisms similar to those responsible for brain growth and development.
• Motor skills are usually learned by repetition.
• It is possible to perform such skills without consciously recalling the individual steps involved.
• Nobel laureate Eric Kandel and his colleagues at Columbia University studied the cellular basis of learning using the sea hare, Aplysia californica.
• They were able to explain the mechanism of simple forms of learning in the mollusc in terms of changes in the strength of synaptic transmission between specific sensory and motor neurons.
• In the vertebrate brain, a form of learning called long-term potentiation (LTP) involves an increase in the strength of synaptic transmission that occurs when presynaptic neurons produce a brief, high-frequency series of action potentials.
• LTP can last for days or weeks and may be a fundamental process by which memories are stored or learning takes place.
• The cellular mechanism of LTP has been studied most thoroughly at synapses in the hippocampus, where presynaptic neurons release the excitatory neurotransmitter glutamate.
• The postsynaptic neurons possess two types of glutamate receptors: AMPA receptors and NMDA receptors.
• AMPA receptors are part of ligand-gated ion channels.
• When glutamate binds to them, Na+ and K+ diffuse through the channels, and the postsynaptic membrane depolarizes.
• NMDA receptors are part of channels that are both ligand-gated and voltage-gated.
• The channels open only if glutamate is bound and the membrane is depolarized.
• The binding of glutamate to these two types of receptors can lead to LTP through changes in both the presynaptic and postsynaptic neurons.
• Neuroscientists have begun studying human consciousness using brain-imaging techniques such as fMRI.
• Brain imaging can show neural activity associated with conscious perceptual choices and unconscious processing of sensory information.
• Such studies offer an increasingly detailed picture of how neural activity correlates with conscious experience.
• There is a growing consensus that consciousness is an emergent property of the brain, one that recruits activities in many areas of the cerebral cortex.
• Several models suggest a scanning mechanism that repetitively sweeps across the brain, integrating widespread activity into a unified, conscious moment.

Concept 48.7 CNS injuries and diseases are the focus of much research

• Unlike the PNS, the mammalian CNS does not have the ability to repair itself when damaged or injured by disease.
• Surviving neurons in the brain can make new connections and sometimes compensate for damage.
• Generally speaking, brain and spinal cord injuries, strokes, and diseases that destroy CNS neurons have devastating effects.
• Research on nerve cell development and neural stem cells may be the future of treatment for damage to the CNS.
• Researchers are investigating how neurons “find their way” during CNS development.
• To reach their target cells, axons must elongate from a few micrometers to a meter or more.
• Molecular signposts along the way direct and redirect the growing axon in a series of mid-course connections that result in a meandering, but not random, elongation.
• The responsive region at the leading edge of the neuron is called the growth cone.
• Signal molecules released by cells along the growth route bind to receptors on the plasma membrane of the growth cone, triggering a signal transduction pathway.
• The axon may respond by growing toward the source of the signal molecules (attraction) or away from it (repulsion).
• Cell adhesion molecules on the axon’s growth cone also play a role by attaching to complementary molecules on surrounding cells that provide tracks for the growing axon to follow.
• Nerve growth factor released by astrocytes and growth-promoting proteins produced by the neurons themselves contribute to the process by simulating axonal elongation.
• The growing axon expresses different genes as it develops, and it is influenced by surrounding cells that it moves away from.
• This complex process has been conserved during millions of years of evolution, for the genes, gene products, and mechanisms of axon guidance are remarkably similar in humans, nematode worms, and insects.
• In 1998, it was discovered that a adult human brain does produce new neurons.
• New neurons have been found in the hippocampus.
• The function of these new neurons is not clear, but it is known that mice living in stimulating conditions have more new neurons in their hippocampus than those that receive little stimulation.
• Since mature human brain cells cannot undergo cell division, the new cells must have arisen from stem cells.
• In 2001, Fred Gage of the Salk Institute announced that they had cultured neural progenitor cells from adult human brains.
• The term progenitor means that these stem cells are committed to develop as neurons or glia.
• In culture, the cells divided 30 to 70 times and differentiated into neurons and astrocytes.

 The nervous system has a number of diseases and disorders.

• About 1% of the world’s population suffers from schizophrenia, a severe mental disturbance characterized by psychotic episodes.
• The symptoms of schizophrenia include hallucinations and delusions, blunted emotions, distractibility, lack of initiative, and poverty of speech.
• The cause of schizophrenia is unknown, although the disease has a strong genetic component.
• There is an active effort to find the mutant genes that predispose a person to schizophrenia.
• Multiple genes must be involved because inheritance does not follow a simple Mendelian pattern.
• Available treatments for schizophrenia focus on the use of dopamine as a neurotransmitter.
• Two lines of evidence suggest that this approach is suitable.
• First, amphetamine, which stimulates dopamine release, can produce symptoms identical to those of schizophrenia.
• Second, many of the drugs that alleviate the symptoms block dopamine receptors.
• Additional neurotransmitters may also be involved because other drugs successful in treating schizophrenia have stronger effects on serotonin and/or norepinephrine transmitters.
• There are other indications that glutamate receptors may play a role in schizophrenia.
• The street drug PCP blocks glutamate receptors and induces strong schizophrenia-like symptoms.
• Many current schizophrenia medications have severe side effects.
• Twenty-five percent of schizophrenics on chronic drug therapy develop tardive dyskinesia, in which the patient has uncontrolled facial writhing movements.
• Two broad forms of depressive illness are known: bipolar disorder and major depression.
• Bipolar disorder involves swings in mood from high to low and affects about 1% of the world’s population.
• People with major depression have a low mood most of time.
• Five percent of the population suffers from major depression.
• In bipolar disorder, the manic phase is characterized by high self-esteem, increased energy, a flow of ideas, and risky behaviors such as promiscuity and reckless spending.
• In the depressive phase, symptoms include lowered ability to feel pleasure, loss of interest, sleep disturbances, feelings of worthlessness, and risk of suicide.
• Both bipolar disorder and major depression have a genetic component, as identical twins have a 50% chance of sharing this mental illness.
• It is likely that childhood stress is also an important factor.
• Several treatments for depression are available, including Prozac, electroconvulsive shock therapy, lithium administration, and talk therapy.
• Alzheimer’s disease is a mental deterioration or dementia.
• It is characterized by confusion, memory loss, and a variety of other symptoms.
• Its incidence is age related, rising from 10% at age 65 to 35% at age 85.
• The disease is progressive, with patients losing the ability to live alone and take care of themselves.
• There are also personality changes, almost always for the worse.
• It is difficult to diagnose Alzheimer’s disease while the patient is still alive.
• However, it results in characteristic brain pathology.
• Neurons die in huge areas of the brain, often leading to shrinkage of brain tissue.
• The diagnostic features are neurofibrillary tangles and senile plaques in the remaining brain tissue.
• Neurofibrillary tangles are bundles of degenerated neuronal and glial processes.
• Senile plaques are aggregates of ß-amyloid, an insoluble peptide that is cleaved from a membrane protein normally found in neurons.
• Membrane enzymes, called secretases, catalyze the cleavage, causing ß-amyloid to accumulate outside the neurons and to aggregate in the form of plaques.
• The plaques seem to trigger the death of the surrounding neurons.
• In 2004, a team of researchers at Northwestern University used genetic engineering to eliminate one of the secretases in a strain of mice prone to Alzheimer’s disease.
• The genetically engineered mice accumulated less ß-amyloid and did not experience the age-related memory deficits typical of mice of that strain.
• Other drugs are being developed to prevent the development of senile plaques, which form before overt symptoms of Alzheimer’s disease develop.
• Approximately 1 million people in the United States suffer from Parkinson’s disease, a motor disease characterized by difficulty in initiating movement, slowness of movement, and rigidity.
• Like Alzheimer’s disease, Parkinson’s disease results from death of neurons in a midbrain nucleus called the substantia nigra.
• These neurons normally release dopamine from their synaptic terminals in the basal nuclei.
• The degeneration of dopamine neurons is associated with the accumulation of protein aggregates containing a protein typically found in presynaptic nerve terminals.
• Most cases of Parkinson’s disease lack a clearly identifiable cause.
• The consensus among scientists is that it results from a combination of environmental and genetic factors.
• At present, there is no cure for Parkinson’s disease, although various approaches are used to manage the symptoms, including brain surgery; deep-brain stimulation; and drugs such as L-dopa, a dopamine precursor that can cross the blood-brain barrier.
• One potential cure is to implant dopamine-secreting neurons, either in the substantia nigra or in the basal ganglia.
• Embryonic stem cells can be stimulated or genetically engineered to develop into dopamine-secreting neurons.
• Transplantation of these cells into rats with an experimentally induced condition that mimics Parkinson’s disease has led to a recovery of motor control.
• It remains to be seen whether this kind of regenerative medicine will work in humans.