a. Real nervous systems only occur in eumetazoans.

b. Cnidarians have simple systems for responding to stimuli such as touch, light, and chemicals.

c. The cnidarian nervous system is a nerve net made of simple neurons with two, three, or several axonlike processes (Figure 42.1).

d. Nerve nets operate slowly because each signal must pass through the entire network of many neurons, instead of through a few neurons with long axons.

e. The cnidarian nerve net can coordinate movements and stereotyped behaviors called fixed-actions patterns (see Chapter 49).

f. Hydra, for example, has directed searching and feeding movements and contractions (Figure 42.2) that are always the same and thus constitute a fixed-action pattern.

g. In the simplest flatworms, the nerve network has retained its external position just below the muscle layers, as in cnidarians.

h. More advanced flatworms have a nervous system deeper in the body, with neuron cell bodies concentrated in bilateral anterior ganglia called a "brain" (Figure 42.3).

i. This nervous system has a ladder form, with left and right ganglia connected by tracts called commissures.

j. In later animal groups, the nervous system increasingly became formed of fibers, for carrying signals long distances, with fewer intervening cell bodies, and was gradually transformed into a central nervous system (CNS).

k. Later evolution led to the dominance of fibers that could rapidly conduct signals along the anterior-posterior axis to and from the anterior brain.

l. Concepts 42.1 reviews some of the basic terminology used to describe nervous systems.

a. Most annelids, arthropods, and molluscs have well-developed central nervous systems with anterior ganglia.

b. Annelids have a somewhat dorsal brain, a subpharyngeal ganglion, and a pair of ventral nerve cords with fused ganglia in each body segment (Figure 42.4).

c. The annelid nerve cords contain some giant axons, common among invertebrates and capable of conducting signals rapidly.

d. In arthropods, the segmental ganglia are specialized for different activities, as are the body segments.

e. Certain molluscs have nervous systems that have been studied extensively.

f. The large sea slug Aplysia californica has relatively few neurons concentrated in four pairs of head ganglia and a large abdominal ganglion; some neurons are giant-sized (Figure 42.5).

g. In this system, only a few neurons are responsible for certain actions, such as a gill-withdrawal reflex (Figure 42.6).

h. Other molluscs, such as squid and octopi, have more complex systems; an octopus's brain is large enough to contain distinct centers for different activities (Figure 42.7).

a. Even the simplest fixed-action pattern must require complex interactions between nerves, muscles, and glands.

b. Richard H. Scheller has examined the fixed-action pattern for egg-laying in Aplysia, and has cloned and sequenced the genes for this system (see Gene cloning in Section 17.13).

c. The entire egg-laying action constitutes one fixed-action pattern generated by a group of neurons that produce the necessary hormone (Figure 42.8).

d. The egg-laying hormone (ELH) is part of a polyprotein that is produced and later cut into functional pieces called bag cell factors.

a. The vertebrate CNS is single, dorsal, and hollow.

b. Early in embryonic development, the dorsal surface rolls into a tube that becomes the nervous system (see Section 20.2).

c. The posterior half of the tube becomes the spinal cord, and the anterior half enlarges to form the brain (Figure 42.9).

d. Anencaphaly is the condition caused by the anterior half of the tube not closing properly.

e. Spina bifida is a condition in which the neural tube remains open and connected to the back.

f. Early in development, the brain divides into the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon).

g. The hindbrain further develops into the metencephalon, which includes the cerebellum and the pons, and the myelencephalon, which becomes the medulla oblongata just anterior to the spinal cord.

h. The midbrain, pons, and medulla comprise the brainstem.

i. Two pockets grow out of the forebrain and become the cerebral hemispheres (telencephalon), whose cortex is highly developed in mammals.

j. The lower part of the forebrain becomes the diencephalon, with the pituitary gland (hypophysis) below.

k. Table 42.1 and Figure 42.10 summarize the main regions of the vertebrate brain.

l. Regardless of developmental twists and enlargements, the brain remains a tube that contains four large, interconnected spaces, or ventricles.

m. Two lateral ventricles are in the cerebrum, the third ventricle is of the diencephalon, and the fourth ventricle is of the hindbrain.

n. The tube is filled with cerebrospinal fluid (CSF), which is similar to blood plasma and is formed in the ventricles as a filtrate of blood.

o. The fluid circulates through the central canal of the spinal cord and outward from the lower brain, eventually returning to the bloodstream.

p. Hydrocephalus (water on the brain) is caused by the incorrect circulation of this fluid during development.

q. The brain and spinal cord are covered by three layers of connective tissue called meninges.

r. A fluid bath of CSF circulates between two of these layers, and protects and supports the brain.

a. Sensory information entering the spinal cord is transmitted through ascending tracts, toward the brain, while the brain transmits motor information through descending tracts to the muscles and glands.

b. An evolutionary tendency is for higher, more recently evolved centers to control lower, more primitive centers, leading to more anterior-posterior traffic between brain centers.

c. When neurons in one center send their axons into a second center, we say that the first projects to the second.

d. A spinal cord cross section reveals central gray matter surrounded by white matter (Figure 42.11).

e. White matter is made of myelinated axons and dendrites; the high density of myelin sheath membranes causes the white color.

f. Myelin sheaths are made by neuroglia, which are supporting, insulating cells.

g. Gray matter consists of cell bodies, dendrites, and unmyelinated axons.

h. Spinal cord white matter contains ascending and descending parallel tracts that are named for the parts of the CNS that they connect.

i. These tracts often cross from the right to left sides of the body; many commissures connecting right and left halves of the brain keep them in communication.

a. The spinal cord becomes the medulla oblongata at the base of the skull.

b. There, a vasomotor center monitors blood pressure; respiratory centers control breathing; and other nuclei control the heartbeat and certain digestive activities.

c. Major tracts connecting the spinal cord and higher brain centers run through the medulla, and seven of twelve cranial nerves (Table 42.2) emerge from it.

d. A reticular formation extending from the medulla through the rest of the brainstem has important functions that include the ascending reticular activating system (ARAS).

e. The diencephalon, with pineal bodies (Sidebar 42.1), surrounds the third ventricle (Figure 42.13).

f. All sensory pathways, except those for smell, lead to nuclei of the thalamus, or two thalami that constitute the walls of the third ventricle, and which coordinate and analyze sensory information and relay it to the cerebral cortex.

g. The hypothalamus and pituitary gland (see Section 41.14) lie below the third ventricle.

h. Hypothalamic nuclei control body temperature, eating, drinking, osmotic regulation, and reproductive and emotional behavior.

a. The most predominant change during vertebrate brain evolution involves the growing dominance of the cerebral hemispheres (Figure 42.14).

b. In fishes, the cerebral hemispheres are small bulbs used for olfactory processing.

c. In amphibians, two new areas appeared: the archicortex for associating information, and the corpus striatum for motor control.

d. In reptiles, the corpus striatum was folded and pushed up inside the cerebrum as an isolated body, and a new neocortex appeared for integrating input from all senses–this center eventually came to dominate the whole cerebrum.

e. Primates have a particularly enlarged, complicated cerebral cortex with a large surface area.

f. The human cortex has folds, or gyri, separated by grooves, or sulci, with about two-thirds of the surface area buried in the sulci.

g. Large, deep sulci called fissures divide each side into four lobes (frontal, parietal, temporal, and occipital) as shown in Figure 42.15.

h. Smaller regions of the cortex are identified by numbers called Brodmann's areas that show differences in cell structure.

i. During the 1950s, Walter Penfield performed brain surgeries that involved stimulating the cerebrum, which has no pain receptors, and mapping the results from the reports of the patients, who were awake.

j. Penfield found that stimulating the postcentral gyrus evoked the somesthetic sense (sense of touch).

k. The body surface is represented in a maplike way on the cerebral cortex (Figure 42.16a).

l. Penfield also found the motor cortex by stimulating the precentral gyrus area and observing that certain muscles twitch as a result; the motor map is very much like the somesthetic map (Figure 42.16).

m. The occipital lobe contains centers of vision, discussed in Section 43.11.

n. Sidebar 42.2 addressed the function of the frontal lobes and contains the story of Phineas Gage and discussion of frontal lobotomies.

o. The temporal lobe processes auditory information, with a major speech area called Wernicke's area nearby (Section 42.8).

p. The temporal lobe contains "association areas" that are apparently places where information is integrated, and may be associated with memory, emotions, or specific abilities like performing mathematical operations.

a. Some kinds of epilepsy involve impulses between the left and right hemispheres, in which case the patient can be cured by severing the corpus callosum.

b. Split-brain experiments involve separating the left and right brain hemispheres (Figure 42.17) and recording what is sensed by the subject.

c. Speech centers are on the left side of the cerebral cortex; the right side controls manipulospatiality, or the ability to draw, arrange, construct, and manipulate objects.

d. The right side governs the sense of active touch, by which the size, shape, and orientation of objects is learned (the sense of simple touch merely tells the body that something is touching it).

e. In primates, manipulospatiality is highly developed and vested in the inferior parietal lobule (IPL) of the neocortex (Figure 42.18) and became focused on the right side as verbal abilities evolved in humans.

f. Speech is controlled by several areas of the left cortex (Figure 42.18).

a. Figure 42.19 shows the structures, concentrated in the cerebral cortex, involved in a simple activity like drinking from a cup.

b. The process of making decisions (like to drink from a cup) is not well understood, though the association areas of the frontal lobes seem to be involved, along with the basal nuclei.

c. Signals descend from the motor cortex through two general paths, the pyramidal and extrapyramidal motor systems (Figure 42.20).

d. The pyramidal system controls precise, voluntary, skilled movements such as writing, typing, playing instruments, engaging in athletics, working with tools, and speaking.

e. The pyramidal system also controls reflex actions, where the muscular movements are the same, but are initiated via a short reflex circuit.

f. The basal nuclei are also involved in large movements from one area of space to another.

g. In the control of movement, the corpus striatum receives input from the substantia nigra, a connection that is important in conditions such as Parkinson disease.

h. To make movements fine and precise, feedback from the extrapyramidal system is necessary.

i. Collateral signals are sent to the cerebellum, which thus receives information about what movement it intended; sensory information about what has actually happened is also sent there, and the two signals are compared, after which the action is refined.

j. Skills that become automatic are encoded in the cerebellum.

k. Persons with cerebellar damage may experience intention tremor, as their limbs oscillate back and forth and cannot be brought to the correct position intentionally.

a. Neurons communicate with each other and with other cells by means of neurotransmitters (Figure 42.21).

b. In the vertebrate CNS, each ligand is either excitatory or inhibitory, and each neural pathway operates with a single neurotransmitter.

c. Pathways have been elucidated by the use of radioactive labeling and fluorescent dyes.

d. Neurotransmitters that are released into a synaptic cleft are then quickly removed, recycled, and degraded, keeping signals distinct.

e. Huntington chorea is a disease characterized by uncontrollable motions that result from the degeneration of the corpus striatum, which controls movements via an inhibitory transmitter that is deficient in patients with the disease.

f. Other motor system tracts use dopamine as a transmitter; dopaminergic neurons arise in the substantia nigra and project into the corpus striatum (Figure 42.22).

g. Parkinson disease is characterized by problems with slow, directed movements that are normally controlled by striatum cells; patients with this disease are treated with a precursor of dopamine.

h. Evidence indicates that schizophrenia disorders arise from faulty regulation of dopamine metabolism in some key pathways.

i. Amphetamine, whose effects mimic schizophrenia, enhances the release of dopamine and inhibits it uptake; thus, a contributing factor in schizophrenia could be an excess of dopamine.

a. Neuropeptides are small peptides with known functions outside the nervous system (Table 42.3) that also have important roles in the nervous system.

b. For example, cholecystokinin (CKK) is a digestive system hormone, and CKK-8 is a related neurotransmitter that affects an appetite center.

c. Angiotensin II is a hormone involved in regulating blood pressure, and found in small amounts in the thalamus and hypothalamus; it causes secretion of vasopressin (ADH), another small peptide secreted by the hypothalamus.

d. Vasoactive intestinal peptide (VIP) is found in many places in the body.

e. Neuropeptides are being identified as mediators between the nervous and immune systems.

a. Endorphins and enkephalins are neuropeptides that are natural analgesics (painkillers).

b. For a long time, some of our most important analgesic drugs (such as morphine) have been opiate derivatives, and it has now been shown that endorphins and enkephalins bind to opiate receptors.

c. Natural opiate ligands in brain tissue were found in 1975, and were called enkephalins, short peptides with morphinelike effects.

d. Like the egg-laying hormone of Aplysia, these small neuropeptides are cut out of polyproteins as shown in Figure 42.23.

e. Endorphins produce analgesia and tranquility and are now being used experimentally to treat neurological and psychiatric problems.

a. There are no good explanations yet for complex learning, but simple learning has begun to be understood.

b. Though many actions are due to reflex, repeated stimulation can lead to habituation, as the animal stops responding.

c. This effect is localized in the ends of sensory neurons (Figure 42.24), where the amount of neurotransmitter released depends on the activity of the voltage-gated calcium ion channels.

d. With repeated stimulation, these calcium channels become inactivated, causing less neurotransmiter to be released and reducing the excitation of the motor neurons.

e. The opposite of habituation is sensitization, causing the animal to pay more attention than usual to a stimulus.

f. Sensitization in the gill-withdrawal reflex, for example, depends on facilitatory interneurons (Figure 42.25).

g. The neurotransmitter released by the facilitatory neurons activates adenylate cyclase to make cAMP in the axon endings of the sensory neurons (Figure 42.26).

h. Cyclic AMP activates protein kinases, including those that phosphorylate certain membrane proteins, ultimately causing action potentials to last longer.

i. It is plausible that learning and memory involve the facilitation of certain neuronal circuits.

j. Long-term memory may involve the formation of new connections among neurons and perhaps changes in the glial cells that surround the neurons.

k. Investigators continue to locate brain activities through new techniques such as positron-emission tomography (Figure 42.27), which shows changes in the patterns of blood flow and locates neuron activities.