Neuron Electrophysiology: Resting Membrane Potential, Ion Channels, and Action Potentials, Study notes of Physiology

Download Neuron Electrophysiology: Resting Membrane Potential, Ion Channels, and Action Potentials and more Study notes Physiology in PDF only on Docsity! 11.1 Overview of the Nervous System 381 11.2 Nervous Tissue 384 11.3 Electrophysiology of Neurons 393 11.4 Neuronal Synapses 406 11.5 Neurotransmitters 413 11.6 Functional Groups of Neurons 417 You can’t turn on the television or radio, much less go online, without seeing some- thing to remind you of the nervous system. From advertisements for medications to treat depression and other psychiatric conditions to stories about celebrities and their battles with illegal drugs, information about the nervous system is everywhere in our popular culture. And there is good reason for this—the nervous system controls our perception and experience of the world. In addition, it directs voluntary movement, and is the seat of our consciousness, personality, and learning and memory. Along with the endocrine system, the nervous system regulates many aspects of homeostasis, including respiratory rate, blood pressure, body temperature, the sleep/wake cycle, and blood pH. In this chapter we introduce the multitasking nervous system and its basic functions and divisions. We then examine the structure and physiology of the main tissue of the nervous system: nervous tissue. As you read, notice that many of the same principles you discovered in the muscle tissue chapter (see Chapter 10) apply here as well. M O D U L E 11.1 Overview of the Nervous System Learning Outcomes 1. Describe the major functions of the nervous system. 2. Describe the structures and basic functions of each organ of the central and peripheral nervous systems. 3. Explain the major differences between the two functional divisions of the peripheral nervous system. In this module we introduce the organs of the nervous system and how they fit within anatomical and functional divisions. These organs and their classifications are covered in more detail in later chapters (see Chapters 12, 13, and 14). Anatomical Divisions of the Nervous System ◀ ◀  Flashback 1. Define neuron, neuroglial cell, and axon. (p. 150) 2. Where is the foramen magnum located, and what is the main nervous system structure that passes through it? (p. 216) 3. What are vertebral foramina? (p. 232) 381 11 Introduction to the Nervous System and Nervous Tissue Computer-generated image: A synapse between two nerve cells is shown. M11_AMER2952_01_SE_C11_381-423.indd 381 6/19/14 10:44 AM 8th proof 382 Chapter 11 | Introduction to the Nervous System and Nervous Tissue The nervous system can be divided anatomically into the cen- tral nervous system (CNS) and the peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord, whereas nerves make up the PNS (Figure 11.1). Let’s look at each of these divisions more closely. The Central Nervous System The organ of the central nervous system that is likely most famil- iar to you, yet still holds the greatest mysteries for physiologists, is the brain. Enclosed completely by the skull, the brain is com- posed primarily of nervous tissue. This remarkable organ consists of about 100 billion cells called neurons (NOOR-onz), or nerve cells, that enable everything from the regulation of breathing and the processing of algebra to performing in the creative arts. The cells that make up nervous tissue are discussed in Module 11.2. At the foramen magnum, the brain merges with the next organ of the central nervous system: the spinal cord. The spinal cord passes through the vertebral foramen of the first cervical vertebra and continues inferiorly to the first or second lumbar vertebra (see Chapter 7). It contains fewer cells than the brain, with only about 100 million neurons. The spinal cord enables the brain to communicate with most parts of the body below the head and neck; it is also able to carry out certain functions on its own (which are discussed in later chapters). The Peripheral Nervous System The peripheral nervous system is made up of the most numer- ous organs of the nervous system, the nerves, which carry signals to and from the central nervous system. A nerve con- sists of a bundle of long neuron “arms” known as axons that are packaged together with blood vessels and surrounded by con- nective tissue sheaths. Nerves are classified according to their origin or destination: Those originating from or traveling to the brain are called cranial nerves, and those originating from or traveling to the spinal cord are called spinal nerves (see Figure 11.1). There are 12 pairs of cranial nerves and 31 pairs of spi- nal nerves. The PNS has separate functional divisions, which we discuss next. Quick Check □ 1. What are the organs of the CNS? □ 2. What are the organs of the PNS? Functional Divisions of the Nervous System As the nervous system performs its many tasks, millions of pro- cesses may be occurring simultaneously. However, all of these tasks or functions generally belong to one of three types: sen- sory, integrative, or motor. Sensory functions involve gathering information about the internal and external environments of the body. Integrative functions analyze and interpret incoming sen- sory information and determine an appropriate response. Motor functions are the actions performed in response to integration. An example of these functions is illustrated in Figure 11.2, which shows a woman 1 seeing a soccer ball moving toward her, 2 integrating this input to interpret the position of the ball, and then 3 kicking the ball. Sensory input is gathered by the sensory, or afferent, division (AF-er-ent; “carrying toward”) of the PNS. Integration is performed entirely by the CNS, mostly by the brain. Motor output is performed by the motor, or efferent, division (EE-fer-ent; “carrying away”) of the PNS. Let’s look more at these three functional divisions: ●  PNS sensory division. Sensory information is first de- tected by structures of the PNS called sensory receptors. The structure of these receptors is diverse—they range from small tips of neurons found in the skin that sense tempera- ture to complex receptors within muscles that sense muscle stretch. Depending on the location of the sensory recep- tors, the PNS sensory division may be further classified as follows: ○  The somatic sensory division (soma- = “body”) con- sists of neurons that carry signals from skeletal muscles, bones, joints, and skin. This division also includes spe- cial sensory neurons that transmit signals from the or- gans of vision, hearing, taste, smell, and balance (see Chapter 15). Sometimes the neurons of this division are referred to as the special sensory division. ○  The visceral sensory division consists of neurons that transmit signals from viscera (organs) such as the heart, lungs, stomach, intestines, kidneys, and urinary bladder. Figure 11.1 Structure of the nervous system. Brain CNS (central nervous system) Spinal cord Cranial nerves PNS (peripheral nervous system) Spinal nerves and their branches M11_AMER2952_01_SE_C11_381-423.indd 382 6/19/14 10:44 AM 8th proof 11.2 | Nervous Tissue 385 which provide structural support that extends out into the den- drites and axon of the neuron as well (see Figure 11.5). The cytoskeleton also contains microtubules that provide structural support and a means for transporting chemicals between the cell body and the axon. Processes: Dendrites and Axons Extending from all neuron cell bodies are long “arms,” cytoplas- mic extensions that are called processes. These processes allow the neuron to communicate with other cells. Most neurons have two types of processes, including one or more dendrites and one axon. Dendrites Dendrites (DEN-drytz; dendr- = “branch or tree”) are typically short, highly forked processes that resemble the branches of a tree limb. They receive input from other neurons, which they transmit in the form of electrical impulses toward the cell body. Note, however, that dendrites usually do not gener- ate or conduct action potentials. Their cytoplasm contains most of the same organelles as the cell body, including mitochon- dria, ribosomes, and smooth endoplasmic reticulum. The exten- sively forked “dendritic trees” of most neurons give them a huge volume of the neuron and also for manufacturing all of the pro- teins the neuron needs. This high level of biosynthetic activity is reflected in the composition of the organelles within its cytoplasm: ●  Free ribosomes and rough endoplasmic reticulum (RER) are found in abundance, reflecting the commitment of the cell body to protein synthesis. Note that the association of ribosomes and RER forms what appears under a micro- scope as dark-staining clusters called Nissl bodies; these are represented in Figure 11.5. ●  Other organelles involved in protein synthesis, including the Golgi apparatus and one or more prominent nucleoli, are present. ●  Mitochondria are found in large numbers, indicating the high metabolic demands of the neuron. Additionally, the cytoplasm of the cell body contains lysosomes, smooth ER, and other organelles found in most cells. The characteristic shape of the cell body is maintained by another component of the cytoplasm—the neuronal cytoskeleton, which is composed of intermediate filaments. These filaments bundle together to form larger structures called neurofibrils, Figure 11.5 Neuron structure. Dendrites Axon collateral Axon hillock Axoplasm Axolemma Neurofibrils Nucleus Intermediate filaments Nissl bodies (ribosomes and rough ER) Mitochondrion Axon Cell body Myelin sheath Telodendria Target cells Axon terminals Practice art labeling M11_AMER2952_01_SE_C11_381-423.indd 385 6/19/14 10:44 AM 8th proof 386 Chapter 11 | Introduction to the Nervous System and Nervous Tissue Functional Regions of Neurons Now let’s briefly discuss how these various components of the typical neuron function together. As you see here, the neuron has three main functional parts: Receptive region Conducting region Secretory region The receptive region of the neuron consists of the dendrites and cell body. The dendrites may receive signals from other neu- rons, or may monitor the external and internal environments via sensory receptors. The received signals are collected in the cell body, which then may send a signal down the axon, the con- ducting region of the neuron. When the signal reaches the axon terminals, they secrete chemicals that trigger changes in their target cells. Classification of Neurons As with many topics that we’ve covered, neurons can be classi- fied according to both their structure and their function. These classification schemes overlap—certain functional groups of neurons often have the same structural features, another exam- ple of how “form follows function” in the body. Structural Classification Neurons vary widely in shape, with the greatest structural variation seen in the number and form of the receptive surface area. Interestingly, the branches of the dendritic tree change throughout an individual’s lifetime: They grow and are “pruned” as a person grows and develops and as functional demands on the nervous system change. Axon Although a neuron may have multiple dendrites, each neu- ron has only a single axon, sometimes called a nerve fiber. Tra- ditionally, an axon was defined as a process that carried a signal away from the cell body. However, the axons of certain neurons can carry a signal both toward and away from the cell body. For this reason, new criteria have been developed to define an axon: They are considered processes that can generate and conduct action potentials. Notice in Figure 11.5 that each axon arises from an area of the cell body called the axon hillock, and then tapers to form the slen- der axon, which is often wrapped in the insulating myelin sheath. Depending on the type of neuron, the axon may range in length from short to very long; in some neurons the axon accounts for most of the length of the neuron. For example, the axons of motor neurons going to the foot must extend from the lumbar portion of the spinal cord all the way down the lower limb and to the foot. Extending from some axons are branches that typically arise at right angles to the axon, called axon collaterals. Both the axon and its collaterals split near their ends to produce multiple fine branches known as telodendria (tee′-loh-DEN-dree-ah). The telodendria terminate in axon terminals, or synaptic knobs, that communicate with a target cell. Each axon generally splits into 1000 or more axon terminals. The plasma membrane that envelops the axon is called the axolemma (aks-oh-LEM-ah), and its cytoplasm is known as axoplasm. Although dendrites have most of the same organ- elles as the cell body, axons do not. Axons contain mitochon- dria, abundant intermediate filaments, vesicles, and lysosomes; however, they do not contain protein-making organelles such as ribosomes or Golgi apparatus. The composition of the axoplasm is dynamic, as substances move both toward and away from the cell body along the axon’s length. Substances may travel through the axoplasm using one of two types of transport, which are together termed axonal transport or flow: ●  Slow axonal transport. Substances within the axoplasm, such as cytoskeletal proteins and other types of proteins, move by slow axonal transport. These substances move only away from the cell body and do so at a rate of about 1–3 mm/day. ●  Fast axonal transport. Vesicles and membrane-bounded organelles use fast axonal transport to travel much more rapidly through the axon. This type of transport relies on motor proteins in the axoplasm that consume ATP to move substances along microtubules either toward the cell body (called retrograde transport), at a maximum rate of about 200 mm/day, or away from the cell body (called anterograde transport), at a maximum rate of about 400 mm/day. See A&P in the Real World: Poliovirus and Retrograde Axonal Transport to see how microorganisms use this method of transport to cause disease. A P in the Real World M11_AMER2952_01_SE_C11_381-423.indd 386 6/19/14 10:44 AM 8th proof 11.2 | Nervous Tissue 387 processes extending from the cell body. On this basis, neurons are classed structurally into three groups: ●  Multipolar neurons. Over 99% of neurons in the human body fall into the group known as multipolar neurons. These neurons have a single axon and typically multiple highly branched dendrites. This group of neurons has the widest variability in terms of shape and size. ●  Bipolar neurons. A bipolar neuron has only two processes: one axon and one dendrite. In humans the majority of bipolar neurons are sensory neurons, located in places such as the ret- ina of the eye and the olfactory epithelium of the nasal cavity. ●  Pseudounipolar neurons. Pseudounipolar neurons (soo′- doh-yoo-nih-POH-lar; formerly referred to as unipolar neu- rons) begin developmentally as bipolar neurons, but their two processes fuse to give rise to a single axon. As the axon extends from the cell body, it splits into two processes: one that brings information from sensory receptors to the cell body, called the peripheral process or axon, and one that travels to the spi- nal cord away from the cell body, called the central process or axon. The pseudounipolar neurons are sensory neurons that sense information such as touch, pressure, and pain. Functional Classification Functionally, neurons are grouped into three classes based on the direction in which they carry informa- tion. The three classes are as follows, in order of information flow: 1. Sensory, or afferent, neurons carry information toward the central nervous system. These neurons receive information from a sensory receptor and transmit this information to their cell body in the PNS, then down their axon to the brain or spinal cord. Because sensory neurons receive information from one area, they are generally pseudounipolar or bipolar in structure. Sensory neurons detect the internal and external environments (such as from the skin and viscera) and facili- tate motor coordination (such as in joints and muscles). 2. Interneurons, also called association neurons, relay messages within the CNS, primarily between sensory and motor neurons, and are the location of most information processing. The vast majority of neurons are interneurons. Multipolar in structure, interneurons generally communicate with many other neurons (for example, one Purkinje cell [per-KIN-jee] of the cerebellum can receive as many as 150,000 contacts from other neurons). 3. Motor, or efferent, neurons carry information away from their cell bodies in the CNS to muscles and glands. As motor tasks are generally complicated and require input from many other neurons, most motor neurons are multipolar. The classification systems of neurons are summarized in Table 11.1. Note that Table 11.1 includes three different examples of multipolar neurons—one from the spinal cord (spinal motor neuron), one from the hippocampus of the brain (pyramidal cell), and another from the cerebellum of the brain (Purkinje cell). Structural Groups of Neuron Components In the CNS and PNS, specific neuron components group together. For example, cell bodies of neurons are typically found within clusters, most of which are in the CNS, where they are called nuclei. Within the PNS, clusters of cell bodies are called ganglia (GANG-glee-ah; singular, ganglion; gangli- = “knot”). In addition, axons tend to be bundled together in the CNS and the PNS. In the CNS, these bundles are referred to as tracts, and in the PNS, as nerves. Table 11.1 NeuroN ClassifiCaTioN Structural Class Multipolar Neurons Bipolar Neurons Pseudounipolar Neurons Structural Features One axon with two or more dendrites; typically have highly branched dendritic tree Dendrites Cell body Axon DendritesDendrites Cell body Cell body AxonAxon Spinal motor neuron Pyramidal cell Purkinje cell One axon and one dendrite Dendrite Cell body Axon Special sensory neuron Single short process that splits into two axons (no dendrites) Receptive endings Cell body Peripheral axon Central axon General sensory neuron Typical Functional Class Motor (efferent) neurons, interneurons Sensory (afferent) neurons Sensory (afferent) neurons Location Most neurons in the CNS, motor neurons in the PNS Special sense organs in the PNS, such as the retina and olfactory epithelium Sensory neurons in the PNS associated with touch, pain, and vibration sensations M11_AMER2952_01_SE_C11_381-423.indd 387 6/19/14 10:44 AM 8th proof 390 Chapter 11 | Introduction to the Nervous System and Nervous Tissue various lipids, including cholesterol, phospholipids, and other unique lipids. In the fluids of the body, electric current is the movement of ions. Ions do not easily pass through the phospholipid bilayer of the plasma membrane, and so the high lipid content of myelin makes it an excellent insulator of electrical current (akin to rub- ber tubing around a copper wire). The overall effect of this insula- tion is to increase the speed of conduction of action potentials: Myelinated axons conduct action potentials about 15–150 times faster than unmyelinated axons. This is a good example of the Structure-Function Core Principle (p. 25). Recall that myelin is formed by Schwann cells in the PNS and by oligodendrocytes in the CNS. The formation of the myelin sheath is known as myelination (my′-eh-lin-AY-shun). 2. What are the differences between hydrophobic and hydrophilic compounds? (p. 47) 3. Are lipids polar covalent or nonpolar covalent compounds? Are they hydrophilic or hydrophobic? (p. 52) As we discussed, certain neuroglia wrap themselves around the axons of neurons to create a structure known as the myelin sheath (Figure 11.8). Myelin is composed of repeating layers of the plasma membrane of the neuroglial cell, so it has the same substances as any plasma membrane: phospholipids, other lip- ids, and proteins. The main components (70–80%) of myelin are Figure 11.8 The myelin sheath in the PNS and CNS. (a) The myelin sheath and myelination in the PNS (b) The myelin sheath in the CNS SEM (30,700×) Dendrites Cell body Axon hillock Nodes of Ranvier Schwann cell Nucleus of Schwann cell Oligodendrocytes Axons Neurolemma Myelin Axon Myelin Axon Nucleus Axon Neurolemma MyelinSchwann cell beginning to myelinate the axon Node of Ranvier Internode Internode Cross-section of a myelin sheath Practice art labeling M11_AMER2952_01_SE_C11_381-423.indd 390 6/19/14 10:44 AM 8th proof 11.2 | Nervous Tissue 391 In the CNS you can actually see which regions of the brain and spinal cord contain myelinated axons and which do not. In sections of both the spinal cord and the brain, regions of darker- and lighter-colored tissue (see Figure 12.2) can be noted. This color difference reflects the distribution of the myelin sheath. The lighter-colored areas, or white matter, are composed of myelinated axons. The darker-colored areas, or gray matter, are made up primarily of cell bodies and dendrites, which are never myelinated, as well as small unmyelinated axons. Quick Check □ 7. What is the function of the myelin sheath? □ 8. How does the myelin sheath differ in the CNS and the PNS? During this process in the PNS, a Schwann cell wraps itself out- ward away from the axon in successively tighter bands, forming a myelin sheath up to 100 layers thick (see Figure 11.8a). The basic process is similar for an oligodendrocyte in the CNS. How- ever, in the CNS the arms of an oligodendrocyte wrap inward toward the axon—the opposite direction from the Schwann cells (see Figure 11.8b). Many other differences can be found between myelination in the PNS and CNS, including the following: ●  Presence or absence of a neurolemma. Note in Figure 11.8a that on the outer surface of a myelinated axon in the PNS we find the nucleus and the bulk of the cytoplasm and organ- elles of the Schwann cell, known as the neurolemma (noor- uh-LEM-ah). Because the nucleus and cytoplasm of the oligodendrocyte remain in a centralized location, no outer neurolemma is found in the CNS (Figure 11.8b). ●  Number of axons myelinated by a single glial cell. Also see that each oligodendrocyte may send out multiple processes to envelop parts of several axons. However, Schwann cells can encircle only a portion of a single axon. ●  Timing of myelination. The timing of myelination is also different within the CNS and the PNS. In the PNS myelina- tion begins during the early fetal period, whereas myelination in the CNS, particularly in the brain, begins much later. Very little myelin is present in the brain of the newborn (which is why babies and toddlers need adequate fat in their diets). In both the CNS and the PNS, axons are generally much lon- ger than a single oligodendrocyte or Schwann cell, so more than one cell is needed to myelinate the entire axon. The segments of an axon that are covered by neuroglia are called internodes, and they range from 0.15 to 1.5 mm in length. Between each inter- node is a gap about 1 μm wide called a node of Ranvier (RAHN- vee-ay), or myelin sheath gap, where no myelin is found. Also unmyelinated is a short region from the axon hillock to the first neuroglial cell; this is known as the initial segment. Short axons in both the CNS and the PNS are nearly always unmyelinated. However, in the PNS, even axons that lack a myelin sheath associate with Schwann cells (Figure 11.9). Take note, though, that the Schwann cells do not wrap themselves around these axons. Instead, they enclose them much like a hot dog in a bun. A single Schwann cell can envelop multiple axons in this manner. A P in the Real World Figure 11.9 Unmyelinated peripheral axons and Schwann cells. Unmyelinated axons Schwann cell Schwann cell nucleus M11_AMER2952_01_SE_C11_381-423.indd 391 6/19/14 10:44 AM 8th proof 392 Chapter 11 | Introduction to the Nervous System and Nervous Tissue Regeneration of Nervous Tissue ◀ ◀  Flashback 1. What is the difference between regeneration and fibrosis? Which tissues are generally able to regenerate? (p. 154 ) 2. What is a basal lamina? (p. 129) Human nervous tissue has a fairly limited capacity for regeneration, or replacement of damaged tissue with new tissue. Damaged axons and dendrites in the CNS almost never regen- erate, a phenomenon apparently due to several factors. For example, oligodendrocytes may inhibit the process of neuronal growth, and chemicals called growth factors that trigger mitosis are largely absent in the CNS. In addition, the growth of astro- cytes creates space-filling scar tissue that also prohibits regenera- tion. For these reasons, injuries to the brain or spinal cord have largely permanent effects. However, in some circumstances lost function may be regained through retraining of the remaining neurons. In contrast, neural tissue in the PNS is capable of regeneration to some extent. Within the PNS, a neuron will regenerate only if the cell body remains intact. When a peripheral axon is dam- aged, the following sequence of events repairs the damaged neu- ron (Figure 11.10): 1 The axon and myelin sheath distal to the injury degen- erate. The damaged axon is cut off from the cell body, and so from all of the protein-synthesis machinery located there. Thus, the axon and myelin sheath distal to the injury begin to degenerate via a process called Wallerian degen- eration (vah-LAIR-ee-an), in which phagocytes digest the cellular debris. 2 Growth processes form from the proximal end of the axon. As Wallerian degeneration occurs, protein synthe- sis within the cell body increases, and several small growth processes sprout from the proximal end of the axon. 3 Schwann cells and the basal lamina form a regeneration tube. Schwann cells begin to proliferate along the length of the surrounding basal lamina near the site of the injury, forming a cylinder called the regeneration tube. 4 A single growth process grows into the regeneration tube. Note in step 2 of Figure 11.10 that several growth processes form; however, only one will make it into the regeneration tube. In the tube, Schwann cells secrete growth factors that stimulate regrowth of the axon. The regeneration tube then guides the axon to grow toward its target cell at a rate of about 1.5–3 mm/day. 5 The axon is reconnected with the target cell. If the axon continues to grow, it most likely will meet up with its tar- get cell and re-establish its synaptic contacts. Over time, the Schwann cells re-form the myelin sheath. This process occurs only under ideal conditions. Even with the cell body intact, the process often stalls after axon degen- eration, and the neuron dies. And if regeneration occurs, the Figure 11.10 Repair of axon damage in the PNS. The axon is reconnected with the target cell.5 A single growth process grows into the regeneration tube.4 Schwann cells and the basal lamina form a regeneration tube.3 Growth processes form from the proximal end of the axon.2 Axon and myelin sheath distal to the injury degenerate (Wallerian degeneration). 1 Reconnected synaptic contacts Axon severed Target cell (skeletal muscle fiber) Growth process in regeneration tube Axon Schwann cell Regeneration tube Schwann cells Growth processes Phagocytes digesting debris M11_AMER2952_01_SE_C11_381-423.indd 392 6/19/14 10:44 AM 8th proof 11.3 | Electrophysiology of Neurons 395 How Do Positive Ions Create a Negative Resting Membrane Potential? Much of the negative resting membrane potential is caused by the movement of positive ions. But how can positive ions create a negative potential? To understand how this works, let’s start with a neuron that has no membrane potential, which means that the charges are distributed equally across the plasma membrane. In our diagram here, five positive charges and five negative charges are found on each side of the membrane: No membrane potential Cytosol ECF + − + − + − + − + − − + − + − + − + − + Plasma membrane Now, imagine that a potassium ion diffuses out of the cytosol down its concentration gradient through a leak channel: Membrane potential K+ K+ leak channel + − + + − + − + − + +1 −1 − − + − − + − + − + We now find six positive charges outside the membrane and four positive charges inside. This makes the overall charge inside the cytosol –1 and in the extracellular fluid +1—a membrane potential has been created. Next imagine that thousands or more potassium ions exit through leak channels, which causes the membrane potential to become progressively more negative. ■ The two main factors that lead to generation of the resting membrane potential are illustrated in Figure 11.12. Quick Check □ 1. What is the resting membrane potential? □ 2. How are sodium and potassium ions distributed across the plasma membrane? What creates this distribution? □ 3. What two factors generate the resting membrane potential? Electrochemical Gradients The resting membrane potential in our cells has important implications for ion transport. Several times in this book, you becomes more negative. This negative voltage is present when the cell is at rest (not being stimulated), and for this reason it is called the resting membrane potential. The cell in this state is said to be polarized, which simply means that the voltage dif- ference across the plasma membrane of the cell is not at 0 mV, but rather measures to either the positive or the negative side (or pole) of zero. All of these factors apply to neurons as well as mus- cle fibers. A typical neuron has a resting membrane potential of about -70 mV, and as we discuss shortly, changes in this poten- tial are responsible for the electrical events of a neuron. Generation of the Resting Membrane Potential Now that we know what the resting membrane potential is, let’s talk about how it’s generated. Imagine a neuron that isn’t polarized— its membrane potential has been temporarily changed to 0 mV. What happens as the membrane returns to its resting state of -70 mV? Two factors work together: ●  Ion concentration gradients favor diffusion of potassium ions out of the cell and sodium ions into the cell. ●  Potassium ions diffuse through leak channels more easily than do sodium ions. The first factor, the concentration gradients across the mem- brane, is due to the activity of the Na+>K+ pumps. The effects of these gradients are that potassium ions tend to diffuse out of the cell, and sodium ions tend to diffuse into the cell. Any difference in these relative rates of diffusion causes the membrane potential to change. To get to the resting state, the membrane potential must become more negative, which means more potassium ions must leave the cell than sodium ions enter. So why does this hap- pen? It occurs because of the second factor, the ease with which potassium ions can cross the membrane through leak channels. Basically, you can think of the membrane as being “leakier” for potassium ions than for sodium ions, and for this reason, more potassium ions exit the cell than sodium ions enter. As these two factors work together, the cytosol loses more positive charges than it gains. This net loss causes the membrane potential to become more negative, until the value of the resting membrane potential is reached. Figure 11.11 Measurement of the voltage across a plasma membrane. ECF Cytosol Plasma membrane – + – + – + – –70 mV + – + – + – + – + – + – + – + – + – + – + – + – + – + – + Voltmeter M11_AMER2952_01_SE_C11_381-423.indd 395 6/19/14 10:44 AM 8th proof Figure 11.12 Generation of the resting membrane potential. ECF Na+ K+ Na+ K+ K+ leak channel Na+ leak channel Voltmeter Cytosol Favored direction of K+ diffusion Favored direction of Na+ diffusion K+ diffuse through leak channels more easily than do Na+. Ion concentration gradients (due to the activity of the Na+/K+ pump) favor diffusion of K+ out of the cell and Na+ into the cell. These two factors cause the cytosol to lose more positive charges than it gains, leading to the negative resting membrane potential. ++ + +++++++++ –––––––– –– – –– + –70 mV Plasma membrane 396 Chapter 11 | Introduction to the Nervous System and Nervous Tissue have seen how solutes move across membranes by diffusion according to their concentration gradient. In fact, the concentra- tion gradient is the main factor that determines the movement of uncharged solutes such as carbon dioxide, glucose, and oxygen. But the story for ions is more complicated because they are also affected by electrical gradients. For this reason, diffusion of an ion across the plasma membrane is determined by both its con- centration gradient and its electrical gradient. These two com- bined forces are called the electrochemical gradient. As an example, consider a potassium ion in the cytosol of a neu- ron (Figure 11.13). You have already seen that 1 the concentration gradient for potassium ions favors their diffusion into the extra- cellular fluid. But now let’s add the force of the electrical gradient. The -70 mV resting potential means that the cytosol is negatively charged relative to the extracellular fluid. As you know, opposite charges attract, so the positively charged potassium ion is attracted to the negatively charged cytosol. 2 This electrical gradient then favors the movement of potassium ions in the opposite direction, into the cytosol. The overall electrochemical gradient is the sum of these two forces—one drawing potassium ions into the cytosol and one drawing them into the extracellular fluid. If these two forces were equal, no net movement of potassium ions would occur. However, 3 the concentration gradient for potassium ions is stronger than the electrical gradient by a small amount. For this reason, the net electrochemical gradient is a small force that draws potassium ions into the extracellular fluid. The small size of the electrochemical gradient for potassium ions in a neuron at rest helps to ensure that the cell doesn’t lose too many potassium ions to the extracellular fluid through leak channels. When we look at sodium ions, however, a different pic- ture emerges. You already know that the concentration gradi- ent favors the movement of sodium ions into the cytosol. The electrical gradient also favors their movement into the cytosol, as the positively charged sodium ions are attracted to its nega- tive charges. This creates a strong electrochemical gradient for sodium ions that draws them into the cytosol. Quick Check □ 4. How is an electrochemical gradient different from a concentration gradient? □ 5. How do the electrochemical gradients for potassium ions and sodium ions differ? Changes in the Membrane Potential: Ion Movements Now let’s connect the two concepts we have been discussing: ion channels and gradients plus the resting membrane potential. Figure 11.13 The electrochemical gradient for potassium ions. Cytosol ECF K+ K+ leak channel – + – + – + – + – + – + – + – + The electrical gradient favors the movement of K+ to the cytosol. 2 The concentration gradient is slightly stronger, so a small force favors the movement of K+ into the ECF. The concentration gradient favors the movement of K+ to the ECF. 1 3 M11_AMER2952_01_SE_C11_381-423.indd 396 6/19/14 10:44 AM 8th proof 11.3 | Electrophysiology of Neurons 397 Local Potentials You read in the muscle tissue chapter that each stimulus from a motor neuron leads to a quick, temporary reversal in the mem- brane potential of a muscle fiber, called an action potential (see Chapter 10). However, when a neuron is stimulated just once, a full action potential rarely results. Instead, a small, local change in the membrane potential of the neuron, called a local potential, is produced (see Figure 11.14). A local potential may have one of two effects: ●  It may cause a depolarization in which positive charges en- ter the cytosol and make the membrane potential less nega- tive (e.g., a change from -70 to -60 mV). ●  Alternatively, it may cause a hyperpolarization in which either positive charges exit or negative charges enter the cytosol, which makes the membrane potential more negative (e.g., a change from -70 to -80 mV). Local potentials are sometimes called graded potentials because they vary greatly in size—some produce a larger change in membrane potential than others. The degree of change in the membrane potential during a local potential depends on multi- ple factors, including length of stimulation, number of ion chan- nels that open, and type(s) of ion channels that open. Another feature of local potentials is that they are reversible; on cessation of the stimulus that caused the ion channels to open, the neu- ron quickly returns to its resting potential. Local potentials are also decremental in nature: The changes in membrane potential they produce are small, and the current generated is lost across the membrane over the distance of a few millimeters. Conse- quently, local potentials cannot send signals over great distances, but are useful for short-distance signaling only (which is why they’re called local potentials). However, even though they occur only over short distances, we will see in the next section that local potentials are vital triggers for action potentials, our long- distance signals. Because the resting membrane potential results from the unequal distribution of ions and their different abilities for crossing the membrane, if we change the ability of the ions to cross the mem- brane, the membrane potential will change as well. This happens by opening gated channels in the plasma membrane. As shown in Figure 11.14a, if gated sodium ion channels open, sodium ions follow their electrochemical gradient and rush into the cell, and the cell gains positive charges. The influx of positive charges makes the membrane potential more positive, a change called depolarization. By this process, the cell becomes less polarized as its membrane potential approaches 0 mV. When a cell returns to its resting membrane potential, repolarization has occurred. If we instead open gated potassium ion channels, potassium ions follow their electrochemical gradient out of the cell, and the cell loses positive charges. This causes the membrane poten- tial to become more negative than it is at rest, a change termed hyperpolarization (Figure 11.14b). Note that hyperpolarization may also result from the opening of channels for anions, such as chloride ions, which would allow these negatively charged ions to flow into the cell. (This additional change in membrane potential doesn’t occur in muscle fibers, which is why we didn’t discuss it in the muscle tissue chapter.) Both types of changes in membrane potential are seen in neu- rons. In the upcoming sections, we see how this applies to nervous system physiology and the ability of the neuron to send signals. Quick Check □ 6. In and around the axon, where is the higher concentration of sodium ions? Where is the higher concentration of potassium ions? What maintains this gradient? □ 7. What is the resting membrane potential, and what is responsible for generating it? □ 8. Define depolarization, repolarization, and hyperpolarization. Figure 11.14 Ion movements leading to changes in the membrane potential. The changes shown here are local potentials. –60 mV –80 mV ECF Ligand Cytosol Ligand-gated cation channel Ligand-gated cation channel Hyperpolarization Resting potential Resting potential Ligand-gated anion channel – + + – + – + – + – + – – + + – – + – + – + – + – + – + Voltmeter + + + + + + + + + + + + + + + + + + + ++++ + + – – – – – – – – – –– Time (ms) –80 –70 0 +30 M em br an e po te nt ia l ( m V) Depolarization Time (ms) –70 –60 0 +30 M em br an e po te nt ia l ( m V) (a) Depolarization: Gain of positive charges makes the inside of the cell less negative, causing depolarization. (b) Hyperpolarization: Loss of positive charges (or gain of negative charges) makes the inside of the cell more negative, causing hyperpolarization. Play animation M11_AMER2952_01_SE_C11_381-423.indd 397 6/19/14 10:44 AM 8th proof 400 Chapter 11 | Introduction to the Nervous System and Nervous Tissue many axons, the outflow of potassium ions continues until the membrane potential of the axolemma hyperpolar- izes, possibly becoming as negative as -90 mV. The axo- lemma hyperpolarizes because the gates of the potassium ion channels are slow to close, allowing additional potas- sium ions to leak out of the cell. Hyperpolarization fin- ishes as the voltage-gated potassium ion channels return to their resting state. After the action potential, the potas- sium leak channels and Na+>K+ pumps re-establish the resting membrane potential. Throughout the preceding sequence of events of a single action potential, very little change occurs in the intracellular or extracel- lular concentration of sodium or potassium ions, and therefore the gradient isn’t too disturbed. However, with repetitive action potentials, the gradient will eventually deplete, and the neuron relies on the Na+>K+ pumps in the axolemma to restore it. Read A&P in the Real World: Local Anesthetic Drugs to find out what happens when sodium ion channels are blocked on purpose. Quick Check □ 11. What takes place during the depolarization phase of an action potential? How is it an example of a positive feedback loop? □ 12. What must be reached in order for voltage-gated sodium ion channels to open? □ 13. What takes place during the repolarization and hyperpolarization phases of an action potential? The Refractory Period Neurons are limited in how often they can fire action potentials. For a brief time after a neuron has produced an action potential, the membrane cannot be stimulated to fire another one. This time is called the refractory period (Figure 11.17). The refrac- tory period may be divided into two phases: the absolute refrac- tory period and the relative refractory period. three general phases: the depolarization phase, the repolar- ization phase, and the hyperpolarization phase. During the depolarization phase, the membrane potential rises toward zero and then becomes briefly positive. The membrane potential returns to a negative value during the repolarization phase, and then becomes temporarily more negative than resting during the hyperpolarization phase. Each phase occurs because of the selec- tive opening and closing of specific ion channels. Note that before the action potential, when the membrane is at rest, the gates for both the sodium and the potassium ion channels are closed. The action potential proceeds as follows: 1 A local potential depolarizes the axolemma of the trig- ger zone to threshold. The action potential begins when the voltage-gated sodium ion channels in the axolemma of the trigger zone enter the activated (open) state (see Fig- ure 11.15b). However, these voltage-gated channels will become activated only if the axon is depolarized. The source of this depolarization in the trigger zone is generally a local potential that arrives from the cell body. Note that the local potential must be strong enough to depolarize the axon to a level known as threshold, usually -55 mV. 2 Voltage-gated sodium ion channels activate, sodium ions enter, and the axon section depolarizes. When threshold is reached, the sodium ion channels in the trigger zone are activated (open) and sodium ions rush into the neuron with their electrochemical gradient. As the membrane poten- tial becomes more positive, more voltage-gated sodium ion channels are activated. This cycle continues, and the more the axon depolarizes, the more voltage-gated sodium ion channels are activated. This influx of positive charges causes rapid depolarization to about +30 mV. You may recognize this as an example of a positive feedback loop—the initial input (activation of sodium ion channels and depolarization) amplifies the out- put (more sodium ion channels are activated and the axo- lemma depolarizes further), an example of the Feedback Loops Core Principle (p. 21). 3 Sodium ion channels inactivate and voltage-gated potas- sium ion channels activate, so sodium ions stop entering and potassium ions exit the axon—repolarization begins. When the axolemma is fully depolarized (about +30 mV), the inactivation gates of the voltage-gated sodium ion chan- nels close, and sodium ions stop entering the axon. As this occurs, voltage-gated potassium ion channels slowly open and potassium ions flow out of the axon along their elec- trochemical gradient, causing the axolemma of the trigger zone to lose positive charges and so to begin repolarization. 4 Sodium ion channels return to the resting state and repolarization continues. As potassium ions exit the axon and repolarization continues, the activation gates of the sodium ion channels close and the inactivation gates open, returning the sodium ion channels to their resting state. 5 The axolemma may hyperpolarize before potassium ion channels return to the resting state; after this, the axo- lemma returns to the resting membrane potential. In A P in the Real World M11_AMER2952_01_SE_C11_381-423.indd 400 6/19/14 10:44 AM 8th proof 11.3 | Electrophysiology of Neurons 401 Local and Action Potentials Compared Now that we have discussed both local potentials and action potentials, let’s highlight their differences. You discovered ear- lier that local potentials are graded, and so produce changes in membrane potential of varying degree; however, each action potential will cause a maximum depolarization of the same amount, to about +30 mV. This is due to a phenomenon called the all-or-none principle. Simply put, this principle refers to an event, in this case an action potential, that either happens com- pletely or doesn’t happen at all. If a neuron does not depolarize to threshold, an action potential does not occur. If the neuron does depolarize to threshold, the result is an action potential of a characteristic strength. The size of the action potential is not determined by the strength, frequency, or length of the stimulus, and therefore is not graded like a local potential. The all-or-none principle leads us to a second difference between local potentials and action potentials: their reversibil- ity. Recall that a local potential is reversible; once the stimulus stops, the ion channels close and the resting membrane potential is restored. However, a key feature of an action potential is that when one occurs, it is irreversible—once threshold is reached, it cannot be stopped and will proceed to completion. Finally, a third important difference between local potentials and action potentials is the distance over which the signal trav- els. Whereas local potentials are decremental and decrease over short distances, action potentials are nondecremental; that is, their strength does not diminish. Without this property, signals could not be sent over long distances in the nervous system. Quick Check □ 15. How do local potentials and action potentials differ? □ 16. Which is useful for long-distance signaling, and why? Propagation of Action Potentials A single action potential in one spot can’t perform its main func- tion, which is to act as a method of long-distance signaling. To do this, it has to be conducted, or propagated, down the length of the axon. This movement creates a flow of charged particles, a current. Action potentials are self-propagating, meaning that each action potential triggers another one in a neighboring sec- tion of the axon. You can imagine this process like a string of dominoes—when the first one is tipped over, the next one falls, which triggers the next to fall, and the process continues until the end of the line is reached. Only the first domino needs the “push,” and once they start to fall, the process sustains itself until the end. Action potential transmission occurs largely in one direc- tion—from the trigger zone to the axon terminals—and at a con- stant speed. Propagation takes place in a single direction because the membrane in the previous section (behind the action poten- tial) is still in the refractory period. Recall that the sodium chan- nels in refractory parts of the membrane are in their inactivated state, which means that the wave of depolarization cannot trig- ger them to open. During the absolute refractory period, no additional stimu- lus, no matter how strong, is able to produce an additional action potential. Notice in Figure 11.17 that this period coincides with the voltage-gated sodium ion channels being in their activated and inactivated states; sodium ion channels may not be activated until they return to their resting states with their activation gates closed and their inactivation gates open. Immediately following the absolute refractory period is the relative refractory period, during which only a strong stimulus will produce an action potential. The relative refractory period is marked by a return of voltage-gated sodium ion channels to their resting state while some potassium ion channels remain acti- vated. Because the potassium ion channels are activated and the membrane is repolarizing or even hyperpolarizing, it’s difficult to depolarize the membrane to threshold and trigger an action potential. However, if a greater than normal stimulus is applied, the membrane may depolarize to threshold, and the axon may fire off another action potential. The absolute and relative refractory periods limit the fre- quency of action potential production. In addition, the relative refractory period ensures that stronger stimuli trigger more fre- quent action potentials. Quick Check □ 14. What are the absolute and relative refractory periods? Figure 11.17 Refractory periods of an action potential. M em br an e po te nt ia l ( m V) Na+ channels activated, K+ channels activating slowly Na+ channels inactivated, K+ channels activated Na+ channels in resting state, K+ channels remain activated Na+ and K+ channels in resting state (closed) Na+ and K+ channels in resting state (closed) Time (ms) 0 –70 –55 0 +30 1 2 3 Absolute refractory period Relative refractory period M11_AMER2952_01_SE_C11_381-423.indd 401 6/19/14 10:44 AM 8th proof 402 Chapter 11 | Introduction to the Nervous System and Nervous Tissue depolarized to threshold by local potentials from the den- drites, cell body, or axon. 2 As sodium ion channels activate, an action potential is triggered and spreads positive charges down the axon. Voltage-gated sodium ion channels are activated (open) and an action potential occurs. When this happens, posi- tive charges flow down the axon through the axoplasm. 3 The next section of the axolemma depolarizes to thresh- old and fires an action potential as the previous section of the axolemma repolarizes. As the depolarizing current Propagation of action potentials down an axon forms the nerve impulse. In this section we look at how propagation occurs and the factors that influence the speed of action potential conduction. Events of Propagation The action potential is propagated along the axon by the follow- ing sequence of events, shown in Figure 11.18: 1 The axolemma depolarizes to threshold due to local potentials. The axolemma of the trigger zone is Figure 11.18 Propagation of an action potential. Depolarized membrane— local potentials Depolarizing membrane— action potential Depolarizing membrane— action potential Repolarizing membrane Resting membrane Resting membrane Axon Trigger zone Resting membrane Resting membrane Depolarizing membrane— action potential Repolarizing membrane Resting membrane Resting membrane Axolemma Voltage-gated Na+ channel Na+ Na+ K+ Voltage-gated K+ channel Axoplasm The axolemma depolarizes to threshold due to local potentials. 1 As Na+ channels activate, an action potential is triggered and spreads down the axon. 2 The next section of the axolemma depolarizes to threshold and fires an action potential as the previous section of the axolemma repolarizes. 3 The current continues to move down the axon, and the process repeats. 4 + – + – + – + – – + + – + – + – – + + – + – + – – + + – + – + – + – + – – + + – + – + – – + + – + – + – – + + – + – + – + – + –+ + + + – – + – + – + – + – + – + – + – + – + – + – + – + – + + – + – + – + – + – + – + – – + – + – + – + – + – + – + – + – + – + – + – + – + – + – + – + – + + – + – + – – + + – + – + – – + + – + – + – + – + – – + – + – + – + – + – + – + – + – + – + + – + – – – – Play animation M11_AMER2952_01_SE_C11_381-423.indd 402 6/19/14 10:45 AM 8th proof □ 2. What do you think would happen to the neuronal action potential if the concentration of sodium ions in the extracellular fluid decreased significantly, to the point of reversing the gradient? □ 3. Sometimes when you pull your dinner out of the microwave you have to hold your fingertips to the food for a second or two before you can tell if it is hot or cold. Explain why this happens. (Hint: What type of fiber carries temperature information?) See answers in Appendix A. how and why the action potential occurs. The how of the action potential is shown in Figure 11.20. The why of the action poten- tial is long-distance signaling. As you will see in the upcoming module, the arrival of the action potential at the axon terminal is what allows the neuron to communicate with its target cells. Apply What You Learned □ 1. Predict the effect of the poison ouabain (way-BAH-in), which blocks Na+/K+ pumps, on the neuronal action potential. (Hint: What would happen to the sodium and potassium ion gradients?) Axon terminals Dendrite Local potentials Na+ Na+ AP AP AP AP AP Trigger zone Direction of AP Axon Voltage-gated Na+ channel Local potentials: Local potentials usually generated in the neuron’s dendrites accumulate and reach the trigger zone of the axon (see Figure 11.14). 1 Action potential: The trigger zone depolarizes to threshold and generates an action potential (AP) (see Figure 11.16). 2 Action potential propagation: The action potential is propagated down the axon to the axon terminals (see Figure 11.18). 3 + – + – + – + – + – + – + – + – + – + – + – + – + – + – The Big Picture of Action Potentials Figure 11.20 405 Play animation M11_AMER2952_01_SE_C11_381-423.indd 405 6/19/14 10:45 AM 8th proof 406 Chapter 11 | Introduction to the Nervous System and Nervous Tissue two types, electrical and chemical. We examine both types in this module, although we focus on chemical synapses. The module concludes with a look at neural integration, or the way in which the many synapses of a neuron impact its integrative processes. Overview of Neuronal Synapses Neuronal synapses generally occur between an axon and another part of a neuron; they may occur between an axon and a den- drite, an axon and a cell body, and an axon and another axon. These types are called axodendritic, axosomatic, and axoaxonic synapses, respectively (Figure 11.21). Regardless of the type of synapse, we use certain terms to describe the neurons sending and receiving the message: ●  Presynaptic neuron. The presynaptic neuron is the neuron that is sending the message from its axon terminal. ●  Postsynaptic neuron. The postsynaptic neuron is the neuron that is receiving the message from its dendrite, cell body, or axon. The transfer of chemical or electrical signals between neu- rons at a synapse is called synaptic transmission, and it is the fundamental process for most functions of the nervous system. Synaptic transmission allows voluntary movement, cognition, sensation, and emotion, as well as countless other processes. Each neuron has an enormous number of synapses. Recall from Module 11.2 that each axon generally splits into 1000 or more axon terminals, and each terminal meets up with another axon, dendrite, or cell body. So an average presynaptic neuron, then, generally forms synapses with about 1000 postsynaptic neurons. A postsynaptic neuron can receive input from even more syn- apses—an average neuron can have as many as 10,000 synaptic connections from different presynaptic neurons. Quick Check □ 1. What are the three most common locations where presynaptic axons connect with a postsynaptic neuron? □ 2. Define synaptic transmission. M O D U L E 11.4 Neuronal Synapses Learning Outcomes 1. Compare and contrast electrical and chemical synapses. 2. List the structures that make up a chemical synapse. 3. Discuss the relationship between a neurotransmitter and its receptor. 4. Describe the events of chemical synaptic transmission in chronological order. 5. Define excitatory postsynaptic potential (EPSP) and inhibitory postsynaptic potential (IPSP), and interpret graphs showing the voltage-versus-time relationship of an EPSP and an IPSP. 6. Explain temporal and spatial summation of synaptic potentials. Up to this point, we have discussed how signals are generated and propagated within a neuron. Remember, though, that neu- rons must communicate with other cells, including other neu- rons, in order to carry out their functions—an example of the Cell-Cell Communication Core Principle (p. 27). Therefore, in this module, we will dis- cuss how signals are trans- mitted between neurons at locations called synapses. Recall that a synapse (SIN-aps; syn- = “to clasp or join”) is where a neuron meets its target cell (see Chapter 10). The discussion in that chap- ter revolved around a specific type of synapse—the neuromuscu- lar junction. Here we explore the synapses that occur between two neurons, or neuronal synapses. These synapses may be of Figure 11.21 Structural types of synapses. Axodendritic synapses (connection between axon and dendrite) Axoaxonic synapses (connection between axon and axon) Axosomatic synapses (connection between axon and cell body)A P in the Real World M11_AMER2952_01_SE_C11_381-423.indd 406 6/19/14 10:45 AM 8th proof 11.4 | Neuronal Synapses 407 Figure 11.22 The structures of electrical and chemical synapses. Presynaptic neuron Synaptic vesicle Neurotransmitter molecules Neurotransmitter receptor Synaptic cleft Postsynaptic neuron Gap junction Synaptic cleft Axon terminal Axon terminal Channels Ions (a) Electrical synapse (b) Chemical synapse Practice art labeling programmed, automatic behaviors such as breathing. They are also present in developing nervous tissue in the embryo and fetus and are thought to assist in the development of the brain. In addi- tion, electrical synapses are found outside the nervous system in locations such as cardiac and visceral smooth muscle, where they allow those tissues to engage in coordinated muscle activity. Quick Check □ 3. What are the two main features of an electrical synapse? Chemical Synapses ◀ ◀  Flashback 1. What is a synaptic vesicle? (p. 352) 2. What is a neurotransmitter? (p. 352) The vast majority of synapses in the nervous system are chem- ical synapses. These synapses are more common because they are more efficient—the current in electrical synapses eventu- ally becomes weaker as it dissipates into the extracellular fluid. A chemical synapse, in contrast, converts an electrical signal into a controlled chemical signal, so there is no loss of strength. The chemical signal is reconverted into an electrical signal in the postsynaptic neuron. In the upcoming sections, we explore how this takes place. But first let’s look a little more closely at the dif- ferences between chemical and electrical synapses. Electrical Synapses An electrical synapse (Figure 11.22a) occurs between cells that are electrically coupled via gap junctions. Observe that in these synapses the axolemmas of the two neurons are nearly touching (they are separated by only about 3.5 nm) and that the gap junc- tions contain precisely aligned channels that form pores through which ions and other small substances may travel. This allows the electrical current to flow directly from the axoplasm of one neuron to that of the next. This arrangement creates two unique features of electrical synapses: ●  Synaptic transmission is bidirectional. In an electrical synapse, transmission is usually bidirectional, which means that either neuron may act as the presynaptic or the post- synaptic neuron and that current may flow in either direc- tion between the two cells. ●  Synaptic transmission is nearly instantaneous. The de- lay between depolarization of the presynaptic neuron and change in potential of the postsynaptic neuron is less than 0.1 ms (millisecond), which is extraordinarily fast (we will see that transmission at most chemical synapses requires from one to a few milliseconds). These features of electrical synapses allow the activity of a group of cells to be synchronized—when stimulated, the cells will produce action potentials in unison. Electrical synapses are found primarily in areas of the brain that are responsible for M11_AMER2952_01_SE_C11_381-423.indd 407 6/19/14 10:45 AM 8th proof 410 Chapter 11 | Introduction to the Nervous System and Nervous Tissue proteins in the axolemma of the presynaptic neuron trans- port them back into the presynaptic neuron. Depending on their type, these neurotransmitters may be repackaged into synaptic vesicles or degraded by enzymes. Once the neurotransmitter has been removed from the synap- tic cleft, synaptic transmission is complete. See A&P in the Real World: Arthropod Venom to learn what happens when contin- ued synaptic transmission causes postsynaptic neurons to be overstimulated. Quick Check □ 4. What is the role of calcium ions in a chemical synapse? □ 5. How do the two types of postsynaptic potentials differ? □ 6. How is synaptic transmission terminated? Putting It All Together: The Big Picture of Chemical Synaptic Transmission At this point we’ve discussed the particulars of synaptic trans- mission at a chemical synapse: how the action potential triggers the release of neurotransmitters from the presynaptic neuron, how the neurotransmitters induce an EPSP or IPSP in the post- synaptic neuron, and how transmission is ended. Now we can summarize the whole process, as shown in Figure 11.26. The membrane potential moves farther away from threshold, and an action potential becomes less likely. Termination of Synaptic Transmission We move now to the final step of synaptic transmission— termination. But why terminate synaptic transmission? Once presynaptic neurons have triggered EPSPs and/or IPSPs and so generated a specific response in the postsynaptic neuron, the response cannot be initiated again until the postsynaptic neuron stops being stimulated. The neurons involved in breathing pro- vide a simple example. When we need to inhale, specific neurons are stimulated to trigger our respiratory muscles to contract. Once we have taken a breath, our nervous system needs to stop stimulating these neurons or we will continue to inhale. This is accomplished by stopping synaptic transmission. The messenger of synaptic transmission is the neurotransmitter released by the presynaptic neuron. Therefore, synaptic transmis- sion may be terminated by ending the effects of the neurotrans- mitter. In general, this happens in three ways (Figure 11.25): ●  Diffusion and absorption. Some neurotransmitters simply diffuse away from the synaptic cleft through the extracellu- lar fluid, where they diffuse through the plasma membrane of a neuron or astrocyte and are then returned to the presyn- aptic neuron. ●  Degradation in the synaptic cleft. Certain neurotransmit- ters are broken down by enzymes that reside in the synap- tic cleft. The components of the destroyed neurotransmitter are often then taken back up by the presynaptic neuron and resynthesized into the original neurotransmitter. ●  Reuptake into the presynaptic neuron. Some neurotrans- mitters are removed by a process called reuptake, in which A P in the Real World Figure 11.25 Methods of termi- nation of synaptic transmission. Synaptic cleft Presynaptic neuron Postsynaptic neuron Diffusion and Absorption Neurotransmitters diffuse away from the synaptic cleft and are returned to the presynaptic neuron. Degradation Neurotransmitters are degraded by enzymatic reactions in the synaptic cleft. Reuptake Neurotransmitters are taken back into the presynaptic neuron. Play animation M11_AMER2952_01_SE_C11_381-423.indd 410 6/19/14 10:45 AM 8th proof Axon terminal of presynaptic neuron Action potential Neurotransmitters Ca2+ Ca2+ Synaptic transmission: Ca2+ channels open in the presynaptic neuron; neurotransmitters are released from synaptic vesicles and bind to receptors on the postsynaptic neuron (see Figure 11.23). 2 Postsynaptic potentials: Neurotransmitters trigger an EPSP or IPSP, moving the membrane potential of the postsynaptic neuron either closer to or farther from threshold (see Figure 11.24). 3 Termination of synaptic transmission: Neurotransmitter concentration in the synaptic cleft decreases and synaptic transmission is terminated (see Figure 11.25). 4 Action potential: An action potential reaches the axon terminal of the presynaptic neuron. 1 Synaptic cleft Open receptor/ ion channel OR Postsynaptic neuron Diffusion Degradation Closed receptor/ ion channel Reuptake EPSP IPSP Threshold Threshold + – + The Big Picture of Chemical Synaptic Transmission Figure 11.26 411 Play animation M11_AMER2952_01_SE_C11_381-423.indd 411 6/19/14 10:45 AM 8th proof 412 Chapter 11 | Introduction to the Nervous System and Nervous Tissue The postsynaptic neuron integrates all of this information into a single effect by a process known as neural integration. As we discussed, a single EPSP produces only a small, local potential and overall has very little effect on the ability of the axolemma to depolarize to threshold and fire an action poten- tial. Recall that most synapses connect to dendrites (axoden- dritic) or the cell body (axosomatic) of the postsynaptic neuron; however, the trigger zone of the axon is where an action poten- tial is generated. Therefore, many EPSPs are required to gener- ate a large enough change in membrane potential to impact the neuron all the way from its dendrites to its axonal trigger zone. This phenomenon of adding the input from several postsynaptic potentials to affect the membrane potential at the trigger zone is known as summation. Neural Integration: Summation of Stimuli In Module 11.1 you read that the integrative functions of the ner- vous system occur in the neurons of the CNS. Put simply, inte- gration refers to the process of putting together all of the stimuli that impact a neuron and either excite or inhibit the firing of an action potential. A neuron very rarely receives input from a sin- gle source; rather, it receives input from multiple other neurons, each of which influences whether or not it generates an action potential. To complicate matters, synaptic transmission in the CNS occurs continuously for most neurons—they are constantly bombarded by synaptic inputs from hundreds to thousands of presynaptic neurons. Additionally, the input from each presyn- aptic neuron may be different; the input may be excitatory or inhibitory, and the strength and location of each input may vary. Figure 11.27 Local potentials summating and leading to an action potential. Action potentials reach the axon terminals of presynaptic neurons. The released neurotransmitters open ligand-gated cation channels in the postsynaptic membrane. 1 Open ligand-gated cation channels allow cations to flow into the postsynaptic neuron. This results in an EPSP—a local potential. 2 The depolarization of the EPSP spreads away from the point of stimulation toward the axon hillock. 3 If enough local potentials summate at the axon hillock to reach threshold, voltage-gated Na+ channels open and an action potential results. 4 M em br an e po te nt ia l ( m V) Time (ms) –70 –55 0 Threshold EPSPs summating +30 Action potential triggered How Summation Connects Local Potentials and Action Potentials By now, you know that local poten- tials are initiated when neurotrans- mitters bind to ligand-gated cation channels in the postsynaptic mem- brane. You also know that an action potential is initiated when the trigger zone is depolarized to threshold and voltage-gated sodium ion channels open in the axolemma. Now we can connect the dots between these two events via summation (Figure 11.27). As you can see, the link between local potentials and action potentials is summation—as excitatory local potentials summate, they depolarize the trigger zone to threshold and initiate an action potential. ■ M11_AMER2952_01_SE_C11_381-423.indd 412 6/19/14 10:45 AM 8th proof 11.5 | Neurotransmitters 415 and choline. The presynaptic neuron then takes the choline back up, to be used in the synthesis of new ACh molecules. The Biogenic Amines The biogenic amines, also called the monoamines, are a class of five neurotransmitters synthesized from amino acids. Most bio- genic amines are widely used by the CNS and the PNS, and have diverse functions including regulation of homeostasis and cog- nition (thinking). The biogenic amines are implicated in a wide variety of psychiatric disorders and are often the targets of drug therapy for these disorders. Three of the biogenic amines form a subgroup called the cate- cholamines (kat′-eh-KOHL-ah-meenz), all of which are synthe- sized from the amino acid tyrosine and share a similar chemical structure. Though many of their synapses are excitatory, like most neurotransmitters, catecholamines can cause inhibition as well. The three catecholamines are as follows: ●  Norepinephrine. Norepinephrine (nor′-ep-ih-NEF-rin; also called noradrenalin) is widely used by the ANS, where it in- fluences functions such as heart rate, blood pressure, and digestion. Neurons that secrete norepinephrine in the CNS are largely confined to the brainstem, where they work to regulate the sleep/wake cycle, attention, and feeding behaviors. inhibitory effects, depending on which postsynaptic neuron receptors they bind. In fact, a single neurotransmitter can have several receptor types. This makes a purely functional classifi- cation of neurotransmitters difficult. For this reason the major neurotransmitters operating within the nervous system are usu- ally classified into four groups by their chemical structures, which we will now explore. For quick reference, Table 11.3 summarizes the location, func- tion, and effects of selected neurotransmitters. Acetylcholine The best-studied, and one of the most widely used neurotrans- mitters by the nervous system overall, is the small-molecule neurotransmitter acetylcholine (ACh) (ah-seet’l-KOH-leen). Synapses that use ACh, called cholinergic synapses, are located at the neuromuscular junction, within the brain and spinal cord, and within the autonomic nervous system (ANS). Its effects are largely excitatory; however, it does exhibit inhibitory effects at some PNS synapses. ACh is synthesized from the precursors choline and acetyl-CoA (an acetic acid molecule bound to coenzyme A) and then pack- aged into synaptic vesicles. Once ACh is released from the synap- tic vesicles, its activity is rapidly terminated by an enzyme in the synaptic cleft known as acetylcholinesterase (AChE; ah-seet’l′- koh-leh-NESS-ter-ayz). AChE degrades ACh back into acetic acid Table 11.3 Major NeuroTraNsMiTTers Neurotransmitter Precursor Molecule(s) Predominant Postsynaptic Effect Location(s) Type of Receptor(s) Acetylcholine Acetyl-CoA and choline Excitatory CNS: brain and spinal cord PNS: neuromuscular junction and ANS Ionotropic and metabotropic Biogenic Amines Catecholamines (norepi- nephrine, epinephrine, dopamine) Tyrosine Excitatory CNS: brain and spinal cord PNS: ANS (sympathetic division) Metabotropic Serotonin Tryptophan Excitatory CNS: brain Metabotropic Histamine Histidine Excitatory CNS: brain Metabotropic Amino Acids Glutamate Glutamine Excitatory CNS: brain (major neurotransmitter of the brain) Ionotropic and metabotropic GABA (G-aminobutyric acid) Glutamate Inhibitory CNS: brain and spinal cord Ionotropic and metabotropic Glycine Serine Inhibitory CNS: brain and spinal cord (most com- mon inhibitory neurotransmitter in the spinal cord) Ionotropic Neuropeptides Substance P Amino acids Excitatory and inhibitory CNS: brain and spinal cord (major neurotransmitter for pain perception) PNS: enteric nervous system (neurons in the digestive tract) Metabotropic Opioids (enkephalin, A-endorphin, dynorphin-A) Amino acids Excitatory and inhibitory CNS: brain and spinal cord (major neurotransmitters for pain control) Metabotropic Neuropeptide Y — Excitatory and inhibitory CNS: brain PNS: ANS Metabotropic M11_AMER2952_01_SE_C11_381-423.indd 415 6/19/14 10:45 AM 8th proof 416 Chapter 11 | Introduction to the Nervous System and Nervous Tissue ●  Substance P. Substance P was the first identified neuro- peptide (its name comes from the fact that it was extracted from brain and gut powder). It is released from type C sen- sory afferent fibers that carry information about pain and temperature (leading many students to use the mnemonic that the “P” stands for “pain”). It is also released by neurons in the brain, spinal cord, and gut. ●  Epinephrine. Epinephrine (also called adrenalin) is also used by the ANS, where it has the same effects as norepi- nephrine. However, it is more widely used as a hormone by the endocrine system (see Chapter 16 for details). ●  Dopamine. Dopamine, used extensively in the CNS, has a variety of functions. It helps to coordinate movement, and is also involved in emotion and motivation. The receptor for dopamine in the brain is a target for certain illegal drugs, such as cocaine and amphetamine, and is likely responsible for the behavioral changes seen with addiction to these drugs. Another biogenic amine is serotonin (sair-oh-TOH-nin), which is synthesized from the amino acid tryptophan. Most neu- rons that use serotonin are found in the brainstem, and their axons project to multiple places in the brain. Serotonin is thought to be one of the major neurotransmitters involved in mood regu- lation (possibly along with norepinephrine), and it is a common target in the treatment of depression. Additionally, serotonin acts to affect emotions, attention and other cognitive functions, motor behaviors, feeding behaviors, and daily rhythms. The final biogenic amine we’ll discuss is histamine (HISS-tah- meen), which is synthesized from the amino acid histidine. His- tamine is involved in a large number of processes in the CNS, including regulation of arousal and attention. In addition, out- side the nervous system, histamine is an important mediator of allergic responses. Drugs called antihistamines block histamine receptors outside the nervous system to alleviate allergy symp- toms, but most also block histamine receptors in the CNS. As histamine plays a part in arousal, blocking its actions often leads to the common side effect of drowsiness seen with these drugs. Amino Acid Neurotransmitters There are three major amino acid neurotransmitters: gluta- mate; glycine; and g-aminobutyric acid, or GABA. Glutamate is the most important excitatory neurotransmitter in the CNS—it is estimated that over half of all synapses in the CNS release glu- tamate. When it binds to its ionotropic postsynaptic receptors, glutamate triggers the opening of a type of channel that can pass both sodium and calcium ions. This elicits an EPSP in the post- synaptic neuron. Glycine and GABA are the two major inhibitory neurotrans- mitters of the nervous system. Both induce IPSPs in the postsyn- aptic neurons primarily by opening chloride ion channels and hyperpolarizing the axolemma. GABA use is widespread in the CNS; as many as one-third of neurons in the brain use it as their major inhibitory neurotransmitter. Glycine is found in about half of the inhibitory synapses in the spinal cord; the remainder of the synapses use GABA. Neuropeptides The neuropeptides are a group of neurotransmitters that have a wide variety of effects within the nervous system. Because they are peptides rather than modified amino acids, they must be synthesized in the cell body, as axons lack the organelles for pro- tein synthesis. Multiple neuropeptides have been identified, and a few are described next. ● ● ● ● A P in the Real World M11_AMER2952_01_SE_C11_381-423.indd 416 6/19/14 10:45 AM 8th proof 11.6 | Functional Groups of Neurons 417 and discuss how groups of neurons work together to carry out the many activities of the nervous system. Neuronal Pools Neuronal pools are groups of interneurons within the CNS. These pools typically are a tangled mat of neuroglial cells, den- drites, and axons in the brain, while their cell bodies may lie in other parts of the CNS. The type of information that can be pro- cessed by a pool is defined by the synaptic connections of that pool. The connections between pools allow for complex mental activity such as planned movement, cognition, and personality. Each neuronal pool begins with one or more neurons called input neurons that initiate the series of signals. The input neuron branches repeatedly to serve multiple neurons in the pool; how- ever, it may have different effects on different neurons. For some neurons, it may generate EPSPs that trigger an action potential, and for others, it may simply bring the neuron closer to thresh- old. This difference is determined by the number of contacts the input neuron makes with the postsynaptic neuron. A small neuronal pool with one input neuron and its post- synaptic neurons is illustrated in Figure 11.30. You can see that the postsynaptic neurons in the center (surrounded by green) have the highest number of synaptic contacts with the input neu- ron. Because of these connections, spatial summation is possible and the firing of the input neuron is likely to generate adequate EPSPs to trigger an action potential. ●  Opioids. The opioids (OH-pee-oydz) make up a family of more than 20 neuropeptides that includes three classes: the endorphins, the enkephalins, and the dynorphins. All share the same property of eliciting pain relief (called analgesia [an′-al-JEE-zee-ah]), and all are nervous system depressants. They also appear to be involved in sexual attraction and aggressive or submissive behaviors. ●  Neuropeptide Y. Neuropeptide Y is a large neuropeptide with 36 amino acids. It appears to function in feeding be- haviors, and may mediate hunger or feeling “full.” Read about how medications can affect synaptic transmission in A&P in the Real World: Psychiatric Disorders and Treatments. Quick Check □ 3. How do neurotransmitters excite a postsynaptic neuron? How do they inhibit a postsynaptic neuron? □ 4. Which neurotransmitters have largely excitatory effects? □ 5. Which neurotransmitters have largely inhibitory effects? Apply What You Learned □ 1. Toxins from the cone snail block glutamate receptors in the postsynaptic membrane. What specifically will this action inhibit? (Hint: What kind of receptor binds glutamate?) □ 2. Predict the effects of the poison strychnine, which blocks glycine receptors on postsynaptic neurons of the CNS. □ 3. What would happen to synaptic transmission if you blocked the degradation and/or reuptake of excitatory neurotransmitters in the synaptic cleft? What if the neurotransmitters were inhibitory? See answers in Appendix A. M O D U L E 11.6 Functional Groups of Neurons Learning Outcomes 1. Define a neuronal pool, and explain its purpose. 2. Compare and contrast the two main types of neural circuits in the central nervous system. So far, we have mostly discussed the behavior of individual neu- rons—how action potentials are generated and conducted, how an action potential leads to synaptic transmission, and how one neuron sends a message to another neuron. Now we explore the behavior of groups of neurons. Neurons don’t typically operate as discrete entities but instead form networks called neuronal pools that perform a common function. Neuronal pools are organized into functional groups called neural circuits (or neural networks). In this module, we examine neuronal pools and neural circuits Figure 11.30 A neuronal pool. Axon of input neuron Postsynaptic neurons Fewer synapses; input neuron alone cannot trigger an action potential. Fewer synapses; input neuron alone cannot trigger an action potential. More synapses; firing of input neuron can trigger an action potential. M11_AMER2952_01_SE_C11_381-423.indd 417 6/19/14 10:45 AM 8th proof 420 Chapter 11 | Introduction to the Nervous System and Nervous Tissue ● A separation of charges occurs across the membrane of neurons. An unstimulated neuron shows a decrease in voltage across the membrane, called the resting membrane potential. Neurons at rest are polarized with a resting membrane potential of about –70 mV. The negative resting membrane potential is due to the loss of K+ through leak channels and the actions of the Na+>K+ pumps. (Figure 11.11, p. 395; Figure 11.12, p. 396) ● Ion movement is driven by the forces of the concentration gradi- ent and the electrical gradient. The sum of these two forces is the electrochemical gradient. (Figure 11.13, p. 396) Play Interactive Physiology tutorial on Nervous System I: Ion Channels. ● A local potential is a small, local change in the membrane poten- tial of a neuron. (Figure 11.14, p. 397) ○ A local potential may either depolarize the neuron, making it less negative, or hyperpolarize the neuron, making it more negative. ○ Local potentials are graded, reversible, decremental with distance, and useful for short-distance signaling only. Play animation on local potentials: Figure 11.14. ● Voltage-gated K+ channels have two states, resting and activated, whereas voltage-gated Na+ channels have three: resting, activated, and inactivated. (Figure 11.15, p. 398) Play Interactive Physiology tutorial on Nervous System I: Resting Membrane Potential. ● An action potential is a rapid depolarization and repolarization of the membrane potential of the cell. (Figure 11.16, p. 399) ○ During the depolarization phase Na+ flood the axon, and the membrane potential rises toward a positive value. ○ During the repolarization phase K+ flow out of the axon, return- ing the axon to its negative resting membrane potential. For many neurons, K+ flow out even after the axolemma has returned to resting, causing hyperpolarization. Play animation on action potentials: Figure 11.16. ● Action potentials are nondecremental, they obey the all-or-none principle, they are irreversible, and they are long-distance signals. ● The refractory period is the span of time during which it is difficult or impossible to elicit another action potential. (Figure 11.17, p. 401) ● Action potentials are propagated along an axon via the flow of current. (Figure 11.18, p. 402) Play animation on action potential propagation: Figure 11.18. ● The speed of action potential propagation depends on the diam- eter of the axon (larger axons conduct more rapidly) and on the presence or absence of a myelin sheath. Conduction may occur in two ways: (Figure 11.19, p. 403) ○ Saltatory conduction occurs rapidly because the current is in- sulated as it flows through each internode and action potentials are generated only at nodes of Ranvier. ○ Continuous conduction occurs much more slowly, as each consecutive region of the membrane must be depolarized to threshold and generate an action potential. ○ Each neuron has only a single axon, which generally carries information away from the cell body to another neuron, muscle fiber, or gland. Materials are transported through an axon via axonal transport. (Figure 11.5, p. 385) Practice art-labeling exercise: Figure 11.5. ● Neurons are classified both structurally and functionally. ○ Structural classes include multipolar neurons, bipolar neu- rons, and pseudounipolar neurons, ○ Functional classes include sensory, or afferent, neurons; inter- neurons; and motor, or efferent, neurons. (Table 11.1, p. 387) ● The neuroglia in the CNS include the following: ○ Astrocytes anchor neurons and blood vessels in place, assist in the formation of the blood-brain barrier, regulate the extra- cellular environment of the brain, and participate in repair of damaged brain tissue. ○ Oligodendrocytes wrap around the axons of neurons and form the myelin sheath. ○ Microglia are phagocytes that “clean up” the extracellular envi- ronment of the brain. ○ Ependymal cells are ciliated cells that line the cavities of the brain and spinal cord and produce and circulate cerebrospinal fluid. (Figure 11.6, p. 388) Practice art-labeling exercise: Figure 11.6. ● The neuroglia of the PNS include the following: ○ Schwann cells form the myelin sheath in the PNS. ○ Satellite cells surround cell bodies of neurons in the PNS. (Figure 11.7, p. 389) Practice art-labeling exercise: Figure 11.7. ● Oligodendrocytes in the CNS and Schwann cells in the PNS wrap around the axon up to 100 times to form the myelin sheath. This covering significantly speeds up conduction of an action potential through the axon. ● The segment of an axon that is myelinated by one glial cell is an internode, and the small gap between internodes is called a node of Ranvier. (Figure 11.8, p. 390) Practice art-labeling exercise: Figure 11.8. ● Unmyelinated axons in the PNS are embedded in Schwann cells. (Figure 11.9, p. 391) ● Axons of the PNS may be regenerated if the cell body remains intact. When regeneration occurs, an axonal growth process is guided toward its target cell by a regeneration tube made of Schwann cells and the basal lamina. (Figure 11.10, p. 392) Play Interactive Physiology tutorial on Nervous System I: Anatomy Review. M O D U L E 11.3 Electrophysiology of Neurons 393 ● Ions move across the axolemma via channels. Two types of channels are leak (always open) and gated channels. (Table 11.2, p. 394) ● Two important ion gradients are those of Na+ and K+: The concen- tration of Na+ is higher in the extracellular fluid, and the concentra- tion of K+ is higher in the cytosol. M11_AMER2952_01_SE_C11_381-423.indd 420 7/25/14 10:03 AM 8th proof ○  In temporal summation, a single presynaptic neuron fires at a rapid pace to influence the postsynaptic neuron. In spatial summation, multiple presynaptic neurons fire simultaneously to influence the postsynaptic neuron. (Figure 11.28, p. 413) Play Interactive Physiology tutorial on Nervous System II: Synaptic Potentials and Cellular Integration. M O D U L E 11.5 Neurotransmitters 413 ●  Neurotransmitters produce their effects by influencing the open- ing or closing of ion channels in the axolemma of the postsynaptic neuron. ●  There are two types of neurotransmitter receptors: (1) ionotropic receptors, and (2) metabotropic receptors. (Figure 11.29, p. 414) ●  The effects of a neurotransmitter are described as excitatory if they generally induce EPSPs and inhibitory if they generally induce IPSPs. Many neurotransmitters are capable of generating both EPSPs and IPSPs. ●  The major neurotransmitters include the following: ○  Acetylcholine is mostly excitatory, and is degraded by acetylcholinesterase. ○  The biogenic amines include the catecholamines (norepinephrine, dopamine, and epinephrine), serotonin, and histamine. ○  The amino acid neurotransmitters include glutamate, glycine, and g-aminobutyric acid (GABA). Glutamate is the major ex- citatory neurotransmitter. Both GABA and glycine are major inhibitory neurotransmitters. ○  Other neurotransmitters are summarized in Table 11.3 (p. 415). Play Interactive Physiology tutorial on Nervous System II: Synaptic Transmission. M O D U L E 11.6 Functional Groups of Neurons 417 ●  Interneurons are organized into neuronal pools that enable specialization within the CNS and so higher mental activity. ●  An input neuron is the presynaptic neuron that initiates the series of signals in a neuronal pool. ○  If the input neuron has sufficient synaptic connections with the postsynaptic neuron, it may trigger it to depolarize to threshold on its own. ○  With sufficient synaptic connections, the IPSPs of an input neuron can inhibit an action potential in postsynaptic neurons. (Figure 11.30, p. 417) ●  The pattern of connection between neuronal pools is called a neural circuit. There are two main types of neural circuits: ○  A diverging circuit begins with one or more input neurons that contact an increasing number of postsynaptic neurons ○  A converging circuit is one in which the signals from multiple neurons converge onto one or more final postsynaptic neurons. (Figure 11.31, p. 418) ●  The big picture of action potentials is shown in Figure 11.20 (p. 405). Play Interactive Physiology tutorial on Nervous System I: The Action Potential. Play animation on the big picture of action potentials: Figure 11.20. M O D U L E 11.4 Neuronal Synapses 406 ●  A synapse is the location where a neuron meets its target cell. The transfer of information between neurons at a synapse is called synaptic transmission. (Figure 11.21, p. 406) ●  Electrical synapses occur between neurons whose axolemmas are electrically joined via gap junctions. Information transfer at an electrical synapse is nearly instantaneous and bidirectional. (Figure 11.22a, p. 407) ●  The majority of synapses in the nervous system are chemical syn- apses, which rely on neurotransmitters to send signals. Chemical synapses are slower than electrical synapses and are unidirec- tional. (Figure 11.22b, p. 407) Practice art-labeling exercise: Figure 11.22. Play Interactive Physiology tutorials on Nervous System II: Anatomy Review, Ion Channels, Synaptic Transmission. ●  The events at a chemical synapse start with an action potential reaching the axon terminal of the presynaptic neuron, which opens calcium ion channels. The influx of calcium ions triggers exocytosis of neurotransmitters stored in synaptic vesicles. The neurotransmitters diffuse through the synaptic cleft and bind to receptors on the membrane of the postsynaptic neuron. When the transmitter binds, a local postsynaptic potential results. (Figure 11.23, p. 408) Play animation on events at a chemical synapse: Figure 11.23. ●  One of two things may happen during a postsynaptic potential: (Figure 11.24, p. 409) ○  The postsynaptic neuron may be depolarized by an excitatory postsynaptic potential (EPSP). ○  The postsynaptic neuron may be hyperpolarized by an inhibitory postsynaptic potential (IPSP). Play animation on postsynaptic potentials: Figure 11.24. ●  The effects of synaptic transmission are terminated by removal of the neurotransmitters from the synaptic cleft. (Figure 11.25, p. 410) Play animation on methods of termination of synaptic transmission: Figure 11.25. ●  The big picture of synaptic transmission is shown in Figure 11.26 (p. 411). Play animation on the big picture of chemical synaptic transmission: Figure 11.26. ●  Neural integration is the process of combining the factors that influence whether or not a neuron fires an action potential. ○  Summation is the phenomenon that combines local postsynap- tic potentials. (Figure 11.27, p. 412) Chapter Summary 421 M11_AMER2952_01_SE_C11_381-423.indd 421 6/19/14 10:45 AM 8th proof 422 Chapter 11 | Introduction to the Nervous System and Nervous Tissue 6. Fill in the blanks: The segment of an axon that is covered by a glial cell is called a/an ___________; the gaps between glial cells where the axolemma is exposed are called ___________. 7. Fill in the blanks: The ___________ is the period of time during which it is impossible to stimulate a neuron to have an action potential, whereas the ___________ is the period of time during which a larger-than-normal stimulus is required to elicit an action potential. 8. With respect to the conduction of action potentials, which of the following statements is false? a. Every region of the membrane must be depolarized and triggered to generate an action potential via saltatory conduction. b. In an unmyelinated axon, every region of the membrane must be depolarized and generate action potentials. c. Type A fibers are the largest, have the most myelin, and conduct action potentials the fastest. d. The myelin sheath allows saltatory conduction, in which only the nodes of Ranvier must generate action potentials. 9. Identify the following as properties of electrical synapses (ES), chemical synapses (CS), or both (B). a. _____ The plasma membranes of presynaptic and postsyn- aptic neurons are joined by gap junctions. b. _____ Transmission is unidirectional and delayed. c. _____ A presynaptic neuron and a postsynaptic neuron are involved. d. _____ The use of neurotransmitters packaged into synaptic vesicles is required. e. _____ Transmission is nearly instantaneous and bidirectional. 10. The trigger for exocytosis of synaptic vesicles from the presyn- aptic neuron is: a. arrival of an action potential at the axon terminal and influx of calcium. b. summation of IPSPs at the presynaptic neuron. c. binding of neurotransmitters to the axon hillock. d. influx of Na+ into the postsynaptic neuron. 11. Match the following neurotransmitters with their correct description. _____ GABA a. Neuropeptide involved in transmis- sion of pain_____ Dopamine b. Neurotransmitter released at the neuromuscular junction _____ Substance P c. Major excitatory neurotransmitter in the brain _____ Acetylcholine d. Major inhibitory neurotransmitter in the brain _____ Glutamate e. Neuropeptide involved in relief of pain _____ Endorphins f. Catecholamine involved in the autonomic nervous system, the sleep/wake cycle, attention, and feeding behaviors _____ Norepinephrine g. Catecholamine involved in move- ment and behavior ASSESS WHAT You LEARNED See answers in Appendix A. LeveL 1 Check Your Recall 1. Which of the following statements about the general functions of the nervous system is false? a. The three primary functions of the nervous system include sensory, integrative, and motor functions. b. The integrative functions of the nervous system are its processing functions. c. Sensory information is transmitted on sensory efferent fibers to a sensory receptor. d. Motor functions are carried out by fibers that carry signals to an effector. 2. Regulation of heart rate, blood pressure, and digestive functions is carried out by the: a. somatic motor division of the peripheral nervous system. b. central nervous system. c. visceral sensory division of the peripheral nervous system. d. autonomic nervous system. 3. Match each type of neuroglial cell with its correct function. _____ Schwann cells a. Phagocytic cells of the CNS _____ Ependymal cells b. Surround the cell bodies of neurons in the PNS_____ Microglial cells c. Create the myelin sheath in the PNS _____ Oligodendrocytes d. Anchor neurons and blood vessels, maintain extracellular environment around neurons, assist in repair of damaged brain tissue _____ Satellite cells e. Create the myelin sheath in the CNS _____ Astrocytes f. Ciliated cells in the CNS that produce and circulate the fluid around the brain and spinal cord 4. With respect to the cell body of a neuron, which of the follow- ing statements is false? a. Aggregates of Golgi apparatus and lysosomes form dark- staining Nissl bodies within it. b. Reflecting its function of protein synthesis, the cell body contains a high density of ribosomes, rough endoplasmic reticulum, and Golgi apparatus. c. Within its cytoplasm are bundles of intermediate filaments that come together to form neurofibrils. d. The cell body has high metabolic demands, and thus has large numbers of mitochondria. 5. An axon is best defined as a process that: a. carries information only toward the cell body. b. can generate action potentials. c. carries information only away from the cell body. d. cannot generate action potentials. M11_AMER2952_01_SE_C11_381-423.indd 422 6/19/14 10:45 AM 8th proof