Can someone help with a powerpoint

blteeyesv8041n

biopsychology_8e_ch04.pdf

Home >Psychology homework help >Can someone help with a powerpoint

Neural Conduction and Synaptic Transmission How Neurons Send and Receive Signals

4.1 Resting Membrane Potential

4.2 Generation and Conduction of Postsynaptic Potentials

4.3 Integration of Postsynaptic Potentials and Generation of Action Potentials

4.4 Conduction of Action Potentials

4.5 Synaptic Transmission: Chemical Transmission of Signals among Neurons

4.6 Neurotransmitters

4.7 Pharmacology of Synaptic Transmission and Behavior

4 IS

B N

0- 55

8- 78

57 1-

Although dopamine levels are low in Parkinson’s dis- ease, dopamine is not an effective treatment because it does not readily penetrate the blood–brain barrier. How- ever, knowledge of dopaminergic transmission has led to the development of an effective treatment: L-dopa, the chemical precursor of dopamine, which readily pene- trates the blood–brain barrier and is converted to dopamine once inside the brain.

Mr. d’Orta’s neurologist prescribed L-dopa, and it worked. He still had a bit of tremor; but his voice became stronger, his feet no longer shuffled, his reptilian stare faded away, and he was once again able to perform with ease many of the activities of daily life (e.g., eating, bathing, writing, speaking, and even making love with his wife). Mr. d’Orta had been destined to spend the rest of his life trapped inside a body that was becoming in- creasingly difficult to control, but his life sentence was repealed—at least temporarily.

Mr. d’Orta’s story does not end here. You will learn what ultimately happened to him in Chapter 10. Mean- while, keep him in mind while you read this chapter: His case illustrates why knowledge of the fundamentals of neural conduction and synaptic transmission is a must for any biopsychologist.

4.1 Resting Membrane Potential

As you are about to learn, the key to understanding how neurons work—and how they malfunction—is the mem- brane potential. The membrane potential is the differ- ence in electrical charge between the inside and the outside of a cell.

Recording the Membrane Potential To record a neuron’s membrane potential, it is neces- sary to position the tip of one electrode inside the neu- ron and the tip of another electrode outside the neuron in the extracellular fluid. Although the size of the extra- cellular electrode is not critical, it is paramount that the tip of the intracellular electrode be fine enough to pierce the neural membrane without severely damaging it. The intracellular electrodes are called microelectrodes; their tips are less than one-thousandth of a millimeter in diameter—much too small to be seen by the naked eye.

Resting Membrane Potential When both electrode tips are in the extracellular fluid, the voltage difference between them is zero. However, when the tip of the intracellular electrode is inserted into a neu- ron, a steady potential of about –70 millivolts (mV) is recorded. This indicates that the potential inside the rest- ing neuron is about 70 mV less than that outside the

Chapter 3 introduced you to the anatomy of neurons.This chapter introduces you to their function—howneurons conduct and transmit electrochemical sig- nals through your nervous system. It begins with a de- scription of how signals are generated in resting neurons; then, it follows the signals as they are conducted through neurons and transmitted across synapses to other neu- rons. It concludes with a discussion of how drugs are used to study the relation between synaptic transmission and behavior. “The Lizard,” a case study of a patient with Parkinson’s disease, Roberto Garcia d’Orta, will help you appreciate why a knowledge of neural conduction and synaptic transmission is an integral part of biopsychology.

The Lizard, a Case of Parkinson’s Disease

“I have become a lizard,” he began. “A great lizard frozen in a dark, cold, strange world.”

His name was Roberto Garcia d’Orta. He was a tall thin man in his sixties, but like most pa- tients with Parkinson’s disease, he ap- peared to be much older than his actual

age. Not many years before, he had been an active, vigor- ous business man. Then it happened—not all at once, not suddenly, but slowly, subtly, insidiously. Now he turned like a piece of granite, walked in slow shuffling steps, and spoke in a monotonous whisper.

What had been his first symptom? A tremor. Had his tremor been disabling? “No,” he said. “My hands shake worse when they are

doing nothing at all”—a symptom called tremor-at-rest. The other symptoms of Parkinson’s disease are not

quite so benign. They can change a vigorous man into a lizard. These include rigid muscles, a marked poverty of spontaneous movements, difficulty in starting to move, and slowness in executing voluntary movements once they have been initiated.

The term “reptilian stare” is often used to describe the characteristic lack of blinking and the widely opened eyes gazing out of a motionless face, a set of features that seems more reptilian than human. Truly a lizard in the eyes of the world.

What was happening in Mr. d’Orta’s brain? A small group of nerve cells called the substantia nigra (black sub- stance) were unaccountably dying. These neurons make a particular chemical called dopamine, which they deliver to another part of the brain, known as the striatum. As the cells of the substantia nigra die, the amount of dopamine they can deliver goes down. The striatum helps control movement, and to do that normally, it needs dopamine.

(Paraphrased from Newton’s Madness: Further Tales of Clinical Neurology by Harold L. Klawans. New York: Harper & Row, © Harold Klawans, 1990.)

76 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Clinical Clinical Implications Implications

IS B

N 0-558-78571-9

type of which is specialized for the passage of particular ions.

In the 1950s, the classic experiments of neurophysiol- ogists Alan Hodgkin and Andrew Huxley provided the first evidence that an energy-consuming process is in- volved in the maintenance of the resting potential. Hodgkin and Huxley began by wondering why the high extracellular concentrations of Na� and Cl� ions and the high intracellular concentration of K� ions were not elim- inated by the tendency for them to move down their con- centration gradients to the side of lesser concentration. Could the electrostatic pressure of –70 mV across the membrane be the counteracting force that maintained the unequal distribution of ions? To answer this question, Hodgkin and Huxley took a creative approach for which they received a Nobel Prize.

First, they calculated for each of the three ions the electrostatic charge that would be required to offset the tendency for them to move down their concentration gra- dients. For Cl� ions, this calculated electrostatic charge was –70 mV, the same as the actual resting potential. Hodgkin and Huxley thus concluded that when neurons

774.1 ■ Resting Membrane Potential

neuron. This steady membrane potential of about –70 mV is called the neuron’s resting potential. In its resting state, with the –70 mV charge built up across its membrane, a neuron is said to be polarized.

Ionic Basis of the Resting Potential Why are resting neurons polarized? Like all salts in solu- tion, the salts in neural tissue separate into positively and negatively charged particles called ions. The resting po- tential results from the fact that the ratio of negative to positive charges is greater inside the neuron than outside. Why this unequal distribution of charges occurs can be understood in terms of the interaction of four factors: two factors that act to distribute ions equally throughout the intracellular and extracellular fluids of the nervous system and two features of the neural membrane that counteract these homogenizing effects.

The first of the two homogenizing factors is random motion. The ions in neural tissue are in constant random motion, and particles in random motion tend to become evenly distributed because they are more likely to move down their concentration gradients than up them; that is, they are more likely to move from areas of high concen- tration to areas of low concentration than vice versa. The second factor that promotes the even distribution of ions is electrostatic pressure. Any accumulation of charges, pos- itive or negative, in one area tends to be dispersed by the repulsion among the like charges in the vicinity and the attraction of opposite charges concentrated elsewhere.

Despite the continuous homogenizing effects of ran- dom movement and electrostatic pressure, no single class of ions is distributed equally on the two sides of the neu- ral membrane. Four kinds of ions contribute significantly to the resting potential: sodium ions (Na�), potassium ions (K�), chloride ions (Cl�), and various negatively charged protein ions. The concentrations of both Na� and Cl� ions are greater outside a resting neuron than inside, whereas K� ions are more concentrated on the inside. The negatively charged protein ions are synthesized inside the neuron and, for the most part, stay there (see Figure 4.1). By the way, the symbols for sodium and potassium were derived from their Latin names: natrium (Na) and kalium (K), respectively.

Two properties of the neural membrane are responsible for the unequal distribution of Na�, K�, Cl�, and protein ions in resting neurons. One of these properties is passive; that is, it does not involve the consumption of energy. The other is active and does involve the consumption of en- ergy. The passive property of the neural membrane that contributes to the unequal disposition of Na�, K�, Cl�, and protein ions is its differential permeability to those ions. In resting neurons, K� and Cl� ions pass readily through the neural membrane, Na� ions pass through it with difficulty, and the negatively charged protein ions do not pass through it at all. Ions pass through the neural membrane at specialized pores called ion channels, each

FIGURE 4.1 In its resting state, more Na� and Cl– ions are outside the neuron than inside, and more K� ions and negatively charged protein ions are inside the neuron than outside.

Protein–

Na+ K+

Cl–

Thinking CreativelyThinking Creatively

IS B

N 0-

55 8-

78 57

1- 9

78 Chapter 4 ■ Neural Conduction and Synaptic Transmission

are at rest, the unequal distribution of Cl� ions across the neural membrane is maintained in equilibrium by the balance between the tendency for Cl� ions to move down their concentration gradient into the neuron and the 70 mV of electrostatic pressure driving them out.

The situation turned out to be different for the K� ions. Hodgkin and Huxley calculated that 90 mV of electro- static pressure would be required to keep intracellular K�

ions from moving down their concentration gradient and leaving the neuron—some 20 mV more than the actual resting potential.

In the case of Na� ions, the situation was much more extreme because the effects of both the concentration gradient and the electrostatic gradient act in the same di- rection. The concentration of Na� ions that exists outside of a resting neuron is such that 50 mV of outward pres- sure would be required to keep Na� ions from moving down their concentration gradient into the neuron, which is added to the 70 mV of electrostatic pressure

acting to move them in the same direction. Thus, the equivalent of a whopping 120 mV of pressure is acting to force Na� ions into resting neurons.

Subsequent experiments confirmed Hodgkin and Huxley’s calculations. They showed that K� ions are continuously being driven out of resting neurons by 20 mV of pressure and that, despite the high resist- ance of the cell membrane to the passage of Na� ions, those ions are continuously being driven in by the 120 mV of pressure. Why, then, do the intracellular and extracellular concentrations of Na� and K� re- main constant in resting neurons? Hodgkin and Hux- ley discovered that there are active mechanisms in the cell membrane to counteract the influx (inflow) of Na� ions by pumping Na� ions out as rapidly as they pass in and to counteract the efflux (outflow) of K�

ions by pumping K� ions in as rapidly as they pass out. Figure 4.2 summarizes Hodgkin and Huxley’s findings and conclusions.

Cl– Cl–

Cl–

Cl– Cl –Cl– Cl–

Cl–Cl–

70 mV of pressure from concentration gradient

70 mV of electrostatic pressure

50 mV of pressure from concentration gradient

90 mV of pressure from concentration gradient

Sodium– potassium pump

Na+

Na+Na+Na+

Na+

Na+Na +

Na+

Na+ Na +

K+K+

K+ K+

K+K +

K+

FIGURE 4.2 The passive and active factors that influence the distribution of Na�, K�, and Cl� ions across the neural membrane. Passive factors continuously drive K� ions out of the resting neuron and Na� ions in; therefore, K� ions must be actively pumped in and Na� ions must be actively pumped out to maintain the resting equilibrium.

IS B

N 0-558-78571-9

It was subsequently discovered that the transport of Na� ions out of neurons and the transport of K� ions into them are not independent processes. Such ion transport is performed by energy-consuming mechanisms in the cell membrane that continually exchange three Na� ions in- side the neuron for two K� ions outside. These trans- porters are commonly referred to as sodium–potassium pumps.

Since the discovery of sodium–potassium pumps, sev- eral other classes of transporters (mechanisms in the membrane of a cell that actively transport ions or mole- cules across the membrane) have been discovered (e.g., Tzingounis & Wadiche, 2007). You will encounter more of them later in this chapter.

Table 4.1 summarizes the major factors that are re- sponsible for maintaining the differences between the in- tracellular and extracellular concentrations of Na�, K�, and Cl� ions in resting neurons. These differences plus the negative charges of the various protein ions, which are

trapped inside the neuron, are largely responsible for the resting membrane potential.

Now that you understand these basic properties of the resting neuron, you are prepared to consider how neurons respond to input.

4.2 Generation and Conduction of Postsynaptic Potentials

When neurons fire, they release from their terminal but- tons chemicals called neurotransmitters, which diffuse across the synaptic clefts and interact with specialized receptor molecules on the receptive membranes of the next neurons in the circuit. When neurotransmitter molecules bind to postsynaptic receptors, they typically have one of two effects, depending on the structure of both the neurotransmitter and the receptor in question. They may depolarize the receptive membrane (decrease the resting membrane potential, from –70 to –67 mV, for example) or they may hyperpolarize it (increase the resting membrane potential, from –70 to –72 mV, for example).

Postsynaptic depolarizations are called excitatory postsynaptic potentials (EPSPs) because, as you will soon learn, they increase the likelihood that the neuron will fire. Postsynaptic hyperpolarizations are called inhibitory postsynaptic potentials (IPSPs) because they decrease the likelihood that the neuron will fire. Both EPSPs and IPSPs are graded responses. This means that the amplitudes of EPSPs and IPSPs are proportional to the intensity of the signals that elicit them: Weak signals elicit small postsynaptic potentials, and strong signals elicit large ones.

EPSPs and IPSPs travel passively from their sites of generation at synapses, usually on the dendrites or cell body, in much the same way that electrical signals travel through a cable. Accordingly, the transmission of post- synaptic potentials has two important characteristics. First, it is rapid—so rapid that it can be assumed to be instantaneous for most purposes. It is important not to confuse the duration of EPSPs and IPSPs with their rate of transmission; although the duration of EPSPs and IPSPs varies considerably, all postsynaptic potentials, whether brief or enduring, are transmitted at great speed. Second, the transmission of EPSPs and IPSPs is decremental: EPSPs and IPSPs decrease in amplitude as they travel through the neuron, just as a sound wave loses amplitude (the sound grows fainter) as it travels through air. Most EPSPs and IPSPs do not travel more than a couple of millimeters from their site of genera- tion before they fade out; thus, they never travel very far along an axon.

794,2 ■ Generation and Conduction of Postsynaptic Potentials

TABLE 4.1 Factors Responsible for Maintaining the Differences in the Intracellular and Extracellular Concentrations of Na�, K�, and Cl� Ions in Resting Neurons

Na� Na� ions tend to be driven into the neurons by both the high concentration of Na� ions outside the neuron and the negative internal resting potential of –70 mv. However, the membrane is resistant to the passive diffusion of Na�, and the sodium–potassium pumps are thus able to maintain the high external concentration of Na� ions by pumping them out at the same slow rate as they move in.

K� K� ions tend to move out of the neuron because of their high internal concentration, although this tendency is partially offset by the internal negative potential. Despite the tendency for the K� ions to leave the neuron, they do so at a substantial rate because the membrane offers little resistance to their passage. To maintain the high internal concentration of K� ions, the sodium–potassium pumps in the cell membrane pump K� ions into neurons at the same rate as they move out.

Cl� There is little resistance in the neural membrane to the passage of Cl� ions. Thus, Cl� ions are readily forced out of the neuron by the negative internal potential. As chloride ions begin to accumulate on the outside, there is an increased tendency for them to move down their concentration gradient back into the neuron. When the point is reached where the electrostatic pressure for Cl� ions to move out of the neuron is equal to the tendency for them to move back in, the distribution of Cl� ions is held in equilibrium. This point of equilibrium occurs at –70 mV.

IS B

N 0-

55 8-

78 57

1- 9

4.3 Integration of Postsynaptic Potentials and Generation of Action Potentials

The postsynaptic potentials created at a single synapse typically have little effect on the firing of the postsynaptic neuron (Bruno & Sakmann, 2006). The receptive areas of most neurons are covered with thousands of synapses, and whether or not a neuron fires is determined by the net effect of their activity. More specifically, whether or not a neuron fires depends on the balance between the excitatory and inhibitory signals reaching its axon. Until recently, it was believed that action potentials were gener- ated at the axon hillock (the conical structure at the junc- tion between the cell body and the axon), but they are actually generated in the adjacent section of the axon (Palmer & Stuart, 2006).

The graded EPSPs and IPSPs created by the action of neurotransmitters at particular receptive sites on a neu- ron’s membrane are conducted instantly and decremen- tally to the axon hillock. If the sum of the depolarizations and hyperpolarizations reaching the section of the axon adjacent to the axon hillock at any time is sufficient to depolarize the membrane to a level referred to as its threshold of excitation—usually about –65 mV—an ac- tion potential is generated near the axon hillock. The action potential (AP) is a massive but momentary—last- ing for 1 millisecond—reversal of the membrane poten- tial from about –70 to about �50 mV. Unlike postsynaptic potentials, action potentials are not graded responses; their magnitude is not related in any way to the intensity of the stimuli that elicit them. To the contrary, they are all-or-none responses; that is, they either occur to their full extent or do not occur at all. See Figure 4.3 for an il- lustration of an EPSP, an IPSP, and an AP. Although many neurons display APs of the type illustrated in Figure 4.3, others do not—for example, some neurons display APs that are longer, that have lower amplitude, or that involve multiple spikes.

In effect, each multipolar neuron adds together all the graded excitatory and inhibitory postsynaptic potentials reaching its axon and decides to fire or not to fire on the basis of their sum. Adding or combining a number of individual signals into one overall signal is called integration. Neurons integrate incoming signals in two ways: over space and over time.

Figure 4.4 shows the three possible combinations of spatial summation. It shows how local EPSPs that are pro- duced simultaneously on different parts of the receptive membrane sum to form a greater EPSP, how simultaneous IPSPs sum to form a greater IPSP, and how simultaneous EPSPs and IPSPs sum to cancel each other out.

Figure 4.5 on page 82 illustrates temporal summa- tion. It shows how postsynaptic potentials produced in rapid succession at the same synapse sum to form a greater signal. The reason that stimulations of a neuron can add together over time is that the postsynaptic po- tentials they produce often outlast them. Thus, if a par- ticular synapse is activated and then activated again before the original postsynaptic potential has completely dissipated, the effect of the second stimulus will be su- perimposed on the lingering postsynaptic potential pro- duced by the first. Accordingly, it is possible for a brief subthreshold excitatory stimulus to fire a neuron if it is administered twice in rapid succession. In the same way,

80 Chapter 4 ■ Neural Conduction and Synaptic Transmission

STIMULUS

Time (milliseconds)

M em

b ra

n e

P o

te n

ti al

( m

ill iv

o lt

–90 –80 –70 –60 –50 –40 –30 –20 –10

0 +10 +20 +30 +40 +50 +60

Action potential

EPSP

An EPSP and an Action Potential

Time (milliseconds)

M em

b ra

n e

P o

te n

ti al

(m ill

iv o

lt s)

–70

An IPSP –65

Time (milliseconds)

M em

b ra

n e

P o

te n

ti al

(m ill

iv o

lt s)

–70

An EPSP –65

FIGURE 4.3 An EPSP, and IPSP, and an EPSP followed by a typical AP.

IS B

N 0-558-78571-9

an inhibitory synapse activated twice in rapid succession can produce a greater IPSP than that produced by a sin- gle stimulation.

Each neuron continuously integrates signals over both time and space as it is continually bombarded with stim- uli through the thousands of synapses covering its den- drites and cell body. Remember that, although schematic diagrams of neural circuitry rarely show neurons with more than a few representative synaptic contacts, most neurons receive thousands of such contacts.

The location of a synapse on a neuron’s receptive membrane has long been assumed to be an important factor in determining its potential to influence the neu- ron’s firing. Because EPSPs and IPSPs are transmitted decrementally, synapses near the axon trigger zone have been assumed to have the most influence on the firing of the neuron (see Mel, 2002). However, it has been demonstrated that some neurons have a mechanism for amplifying dendritic signals that originate far from their cell bodies; thus, in these neurons, all dendritic signals reaching the cell body have a similar amplitude,

814.3 ■ Integration of Postsynaptic Potentials and Generation of Action Potentials

�70

�65 A Stimulated B Stimulated

�75

�70

�65 C Stimulated

�75

�70

�65 D Stimulated

�75

�70

�65 C + D Stimulated

A + B Stimulated

�70

�65

�70

�65

�75

�70

�65 A Stimulated

�75

�70

�65 C Stimulated

�75

�70

�65 A + C Stimulated

Two simultaneous EPSPs sum to produce a greater EPSP

M em

b ra

n e

p o

te n

ti al

( m

ill iv

o lt

B C

Excitatory synapse

Inhibitory synapse

To oscilloscopeD

Two simultaneous IPSPs sum to produce a greater IPSP

A simultaneous IPSP and EPSP cancel each other out

FIGURE 4.4 The three possible combinations of spatial summation.

Before you learn how action potentials are conducted along the axon, pause here to make sure that you under- stand how action potentials are created. Fill in each blank with the most appropriate term. The correct an- swers are provided at the end of the exercise. Before proceeding, review material related to your errors and omissions.

1. Roberto Garcia d’Orta referred to himself as “a great lizard frozen in a dark, cold, strange world.” He suf- fered from ______.

2. Tremor-at-rest is a symptom of ______. 3. Microelectrodes are required to record a neuron’s

resting ______. 4. The ______ is about –70 mV. 5. In its resting state, a neuron is said to be ______. 6. Two factors promote the even distribution of ions

across neural membranes: ______ and electrostatic pressure.

7. In the resting state, there is a greater concentration of Na� ions ______ the neural membrane than ______ the neural membrane.

8. Natrium is Latin for ______. 9. Ions pass through neural membranes via specialized

pores called ______. 10. From their calculations, Hodgkin and Huxley inferred

the existence of ______ in neural membranes. 11. Neurotransmitters typically have one of two effects on

postsynaptic neurons: They either depolarize them or ______ them.

12. Postsynaptic depolarizations are commonly referred to in their abbreviated form: ______.

13. Action potentials are generated near, but not at, the ______.

14. An action potential is elicited when the depolarization of the neuron reaches the ______.

15. Unlike postsynaptic potentials, which are graded, ac- tion potentials are ______ responses.

16. Neurons integrate postsynaptic potentials in two ways: through spatial summation and through ______ summation.

Scan Your Brainanswers: (1) Parkinson’s disease, (2) Parkinson’s disease, (3) potential, (4) resting potential, (5) polarized, (6) random motion, (7) outside, inside, (8) sodium, (9) ion channels, (10) sodium–potassium pumps, (11) hyperpolarize, (12) EPSPs, (13) axon hillock, (14) threshold of excitation, (15) all-or-none, (16) temporal.

regardless of where they originate (Williams & Stuart, 2002, 2003).

IS B

N 0-

55 8-

78 57

1- 9

82 Chapter 4 ■ Neural Conduction and Synaptic Transmission

4.4 Conduction of Action Potentials

Ionic Basis of Action Potentials How are action potentials produced, and how are they con- ducted along the axon? The answer to both questions is ba- sically the same: through the action of voltage-activated ion channels—ion channels that open or close in response to changes in the level of the membrane potential (see Armstrong, 2007).

Recall that the membrane potential of a neuron at rest is relatively constant despite the high pressure act- ing to drive Na� ions into the cell. This is because the resting membrane is relatively impermeable to Na� ions and because those few that do pass in are pumped out. But things suddenly change when the membrane poten-

tial of the axon is reduced to the thresh- old of excitation. The voltage-activated sodium channels in the axon membrane open wide, and Na� ions rush in, sud- denly driving the membrane potential from about –70 to about �50 mV. The rapid change in the membrane potential that is associated with the influx of Na�

ions then triggers the opening of voltage- activated potassium channels. At this point, K� ions near the membrane are driven out of the cell through these channels—first by their relatively high internal concentration and then, when the action potential is near its peak, by the positive internal charge. After about 1 millisecond, the sodium channels close. This marks the end of the rising phase of the action potential and the beginning of repolarization by the continued efflux of K� ions. Once repolarization has been achieved, the potassium channels gradu- ally close. Because they close gradually, too many K� ions flow out of the neu- ron, and it is left hyperpolarized for a brief period of time. Figure 4.6 illus- trates the timing of the opening and closing of the sodium and potassium channels during an action potential.

Two EPSPs elicited in rapid succession sum to produce a larger EPSP

M em

b ra

n e

p o

te n

ti al

( m

ill iv

o lt

Two IPSPs elicited in rapid succession sum to produce a larger IPSP

–70

–65

A A

–70

–65

A A

–70

–65

B B

–70

–65

B B

A B

Excitatory synapse

Inhibitory synapse

To oscilloscope

FIGURE 4.5 The two possible combinations of temporal summation.

In some ways, the firing of a neuron is like the firing of a gun. Both reac- tions are triggered by graded re-

sponses. As a trigger is squeezed, it gradually moves back until it causes the gun to fire; as a neuron is stimulated, it becomes less polarized until the threshold of excitation is reached and firing occurs. Furthermore, the firing of a gun and neural firing are both all-or-none events. Just as squeezing a trigger harder does not make the bullet travel faster or farther, stimulating a neuron more intensely does not increase the speed or amplitude of the resulting action potential.

Thinking CreativelyThinking Creatively

IS B

N 0-558-78571-9

The number of ions that flow through the membrane during an action potential is extremely small in relation to the total number inside and around the neuron. The action potential in- volves only those ions right next to the membrane. Therefore, a single action potential has little effect on the relative concentrations of various ions inside and outside the neuron, and the resting ion concen- trations next to the membrane are rapidly reestablished by the random movement of ions. The sodium–potassium pumps play only a minor role in the reestablishment of the resting potential.

Refractory Periods There is a brief period of about 1 to 2 milliseconds after the initiation of an action potential during which it is im- possible to elicit a second one. This period is called the absolute refractory period. The absolute refractory pe- riod is followed by the relative refractory period—the period during which it is possible to fire the neuron again, but only by applying higher-than-normal levels of stimu- lation. The end of the relative refractory period is the point at which the amount of stimulation necessary to fire a neuron returns to baseline.

The refractory period is responsible for two impor- tant characteristics of neural activity. First, it is responsi- ble for the fact that action potentials normally travel along axons in only one direction. Because the portions of an axon over which an action potential has just trav- eled are left momentarily refractory, an action potential cannot reverse direction. Second, the refractory period is responsible for the fact that the rate of neural firing is re- lated to the intensity of the stimulation. If a neuron is subjected to a high level of continual stimulation, it fires and then fires again as soon as its absolute refractory pe- riod is over—a maximum of about 1,000 times per sec- ond. However, if the level of stimulation is of an intensity just sufficient to fire the neuron when it is at rest, the neuron does not fire again until both the absolute and the relative refractory periods have run their course. In- termediate levels of stimulation produce intermediate rates of neural firing.

Axonal Conduction of Action Potentials The conduction of action potentials along an axon differs from the conduction of EPSPs and IPSPs in two impor- tant ways. First, the conduction of action potentials along an axon is nondecremental; action potentials do not grow weaker as they travel along the axonal membrane. Sec- ond, action potentials are conducted more slowly than postsynaptic potentials.

The reason for these two differences is that the conduc- tion of EPSPs and IPSPs is passive, whereas the axonal con- duction of action potentials is largely active. Once an action potential has been generated, it travels passively along the axonal membrane to the adjacent voltage-activated sodium channels, which have yet to open. The arrival of the elec- trical signal opens these channels, thereby allowing Na�

ions to rush into the neuron and generate a full-blown ac- tion potential on this portion of the membrane. This sig- nal is then conducted passively to the next sodium channels, where another action potential is actively trig- gered. These events are repeated again and again until a full-blown action potential is triggered in all the terminal buttons (Huguenard, 2000). However, because there are so many ion channels on the axonal membrane and they are so close together, it is usual to think of axonal conduc- tion as a single wave of excitation spreading actively at a constant speed along the axon, rather than as a series of discrete events.

The wave of excitation triggered by the generation of an action potential near the axon hillock always spreads passively back through the cell body and dendrites of the neuron. Although little is yet known about the functions of these backward action potentials, they are currently the subject of intensive investigation.

The following analogy may help you appreciate the major characteristics of axonal conduction. Consider a row of mouse traps on a wobbly shelf, all of them set and ready to be triggered. Each trap stores energy by holding

834.4 ■ Conduction of Action Potentials

Potassium channels start to close

–70

54321

–50

–30

–10

+10

+30

+50

Sodium channels open

Sodium channels close

+60

Potassium channels open

HYPERPOLARIZATION

REPOLARIZATION

RISING PHASE

Time (milliseconds) M

em b

ra n

e P

o te

n ti

al (m

ill iv

o lt

FIGURE 4.6 The opening and closing of voltage-activated sodium and potassium channels during the three phases of the action potential: rising phase, repolarization, and hyperpolarization.

IS B

N 0-

55 8-

78 57

1- 9

back its striker against the pressure of the spring, in the same way that each sodium channel stores energy

by holding back Na� ions, which are under pressure to move down their concentration and electrostatic gradi- ents into the neuron. When the first trap in the row is triggered, the vibration is transmitted passively through the shelf, and the next trap is sprung—and so on down the line.

The nondecremental nature of action potential conduction is readily apparent from this analogy; the

last trap on the shelf strikes with no less intensity than did the first. This analogy also illustrates the refrac- tory period: A trap cannot respond again until it has been reset, just as a section of axon cannot fire again until it has been repolarized. Furthermore, the row of traps can transmit in either direction, just like an axon. If electrical stimulation of sufficient intensity is applied to the terminal end of an axon, an action po- tential will be generated and will travel along the axon back to the cell body; this is called antidromic con- duction. Axonal conduction in the natural direction—

from cell body to terminal buttons—is called orthodromic conduction. The elicitation of an action potential and the direction of orthodromic conduction are summarized in Figure 4.7.

Conduction in Myelinated Axons In Chapter 3, you learned that the axons of many neurons are insulated from the extracellular fluid by segments of fatty tissue called myelin. In myelinated axons, ions can pass through the axonal membrane only at the nodes of Ranvier—the gaps between adjacent myelin segments. Indeed, in myeli- nated axons, axonal sodium channels are concentrated at the nodes of Ranvier (Salzer, 2002). How, then, are action potentials transmitted in myelinated axons?

When an action potential is generated in a myelinated axon, the signal is conducted pas- sively—that is, instantly and decrementally—along the first segment of myelin to the next node of Ranvier. Although the signal is somewhat diminished

84 Chapter 4 ■ Neural Conduction and Synaptic Transmission

PSPs are conducted decrementally to the axon.

PSPs are elicited on the cell body and dendrites.

The AP is conducted nondecrementally down the axon to the terminal button.

When the summated PSPs exceed the threshold of excitation at the axon, an AP is triggered.

Arrival of the AP at the terminal button triggers exocytosis.

5 FIGURE 4.7 The direction of signals conducted orthodromically through a typical multipolar neuron.

Thinking CreativelyThinking Creatively

IS B

N 0-558-78571-9

by the time it reaches that node, it is still strong enough to open the voltage-activated sodium channels at the node and to generate another full-blown action potential. This action potential is then conducted passively along the axon to the next node, where another full-blown action potential is elicited, and so on.

Myelination increases the speed of axonal conduction. Because conduction along the myelinated segments of the axon is passive, it occurs instantly, and the signal thus “jumps” along the axon from node to node. There is, of course, a slight delay at each node of Ranvier while the ac- tion potential is actively generated, but conduction is still much faster in myelinated axons than in unmyelinated axons, in which passive conduction plays a less prominent role (see Poliak & Peles, 2003). The transmission of action potentials in myelinated axons is called saltatory conduc- tion (saltare means “to skip or jump”). Given the impor- tant role of myelin in neural conduction, it is hardly surprising that the neurodegenerative diseases (diseases that damage the nervous system) that attack myelin have devastating effects on neural activity and behavior—see the discussion of multiple sclerosis in Chapter 10.

The Velocity of Axonal Conduction At what speed are action potentials conducted along an axon? The answer to this question depends on two prop- erties of the axon (see ffrench-Constant, Colognato, & Franklin, 2004). Conduction is faster in large-diameter axons, and—as you have just learned—it is faster in those that are myelinated. Mammalian motor neurons (neurons that synapse on skeletal muscles) are large and myeli- nated; thus, some can conduct at speeds of 100 meters per second (about 224 miles per hour). In contrast, small, unmyelinated axons conduct action potentials at about 1 meter per second.

There is a misconception about the velocity of motor neuron action potentials in humans. The maximum ve- locity of motor neuron action potentials was found to be about 100 meters per second in cats and was then as- sumed to be the same in humans: It is not. The maximum velocity of conduction in human motor neurons is about 60 meters per second (Peters & Brooke, 1998).

Conduction in Neurons without Axons Action potentials are the means by which axons con- duct all-or-none signals nondecrementally over rela- tively long distances. Thus, to keep what you have just learned about action potentials in perspective, it is im- portant for you to remember that many neurons in mammalian brains either do not have axons or have very short ones, and many of these neurons do not nor- mally display action potentials. Conduction in these

interneurons is typically passive and decremental (Juusola et al., 1996).

The Hodgkin-Huxley Model in Perspective The preceding account of neural conduction is based heav- ily on the Hodgkin-Huxley model, the theory first proposed by Hodgkin and Huxley in the early 1950s (see Huxley, 2002). Perhaps you have previously encountered some of this information about neural conduction in introductory biology and psychology courses, where it is often presented as a factual account of neural conduction and its mecha- nisms, rather than as a theory. The Hodgkin-Huxley model was a major advance in our understanding of neural con- duction (Armstrong, 2007). Fully deserving of the 1963 Nobel Prize, the model provided a simple effective intro- duction to what we now understand about the general ways in which neurons conduct signals. The problem is that the simple neurons and mechanisms of the Hodgkin-Huxley model are not representative of the variety, complexity, and plasticity of many of the neurons in the mammalian brain.

The Hodgkin-Huxley model was based on the study of squid motor neurons. Motor neurons are simple, large, and readily accessible in the PNS—squid motor neurons are particularly large. The simplicity, size, and accessibil- ity of squid motor neurons contributed to the initial suc- cess of Hodgkin and Huxley’s research, but these same properties make it difficult to apply the model directly to the mammalian brain. Hundreds of different kinds of neu- rons are found in the mammalian brain, and many of these have actions not found in motor neurons (see Debanne, 2004; Markram et al., 2004; Nusser, 2009). Thus, the Hodgkin-Huxley model must be applied to cerebral neu- rons with caution. The following are some properties of cerebral neurons that are not shared by motor neurons:

● Many cerebral neurons fire continually even when they receive no input (Lisman, Raghavachari, & Tsien, 2007; Schultz, 2007; Surmeier, Mercer, & Chan, 2005).

● The axons of some cerebral neurons can actively con- duct both graded signals and action potentials (Alle & Geiger, 2006, 2008).

● Action potentials of all motor neurons are the same, but action potentials of different classes of cerebral neurons vary greatly in duration, amplitude, and fre- quency (Bean, 2007).

● Many cerebral neurons have no axons and do not dis- play action potentials.

● The dendrites of some cerebral neurons can actively conduct action potentials (Chen, Midtgaard, & Shepherd, 1997).

Clearly, cerebral neurons are far more complex than motor neurons, which have traditionally been the focus of neurophysiological research, and thus, results of studies of motor neurons should be applied to the brain with caution.

854.4 ■ Conduction of Action Potentials

IS B

N 0-

55 8-

78 57

1- 9

4.5 Synaptic Transmission: Chemical Transmission of Signals among Neurons

You have learned in this chapter how postsynaptic poten- tials are generated on the receptive membrane of a resting neuron, how these graded potentials are conducted pas- sively to the axon, how the sum of these graded potentials can trigger action potentials, and how these all-or-none po- tentials are actively conducted down the axon to the termi- nal buttons. In the remaining sections of this chapter, you will learn how action potentials arriving at terminal buttons trigger the release of neurotransmitters into synapses and how neurotransmitters carry signals to other cells. This sec- tion provides an overview of five aspects of synaptic trans-

mission: (1) the structure of synapses; (2) the synthesis, packaging, and transport of neurotransmitter molecules;

(3) the release of neurotransmitter molecules; (4) the acti- vation of receptors by neurotransmitter molecules; and (5) the reuptake, enzymatic degradation, and recycling of neurotransmitter molecules.

Structure of Synapses Some communication among neurons occurs across synapses such as the one illustrated in Figure 4.8. Neuro- transmitter molecules are released from buttons into synaptic clefts, where they induce EPSPs or IPSPs in other neurons by binding to receptors on their postsynaptic membranes. The synapses featured in Figure 4.8 are axodendritic synapses—synapses of axon terminal buttons on dendrites. Notice that many axodendritic synapses termi- nate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites)—see Figure 3.31 on page 73. Also common are axosomatic synapses— synapses of axon terminal buttons on somas (cell bodies).

Although axodendritic and axosomatic synapses are the most common synaptic arrangements, there are sev- eral others (Shepherd & Erulkar, 1997). For example, there are dendrodendritic synapses, which are interesting because they are often capable of transmission in either direction. Axoaxonic synapses are particularly important because they can mediate presynaptic facilitation and in- hibition. As illustrated in Figure 4.9, an axoaxonic synapse on, or near, a terminal button can selectively fa- cilitate or inhibit the effects of that button on the postsy- naptic neuron. The advantage of presynaptic facilitation and inhibition (compared to EPSPs and IPSPs, which you have already learned about) is that they can selec-

tively influence one particular synapse rather than the entire presynaptic neuron.

The synapses depicted in Fig- ure 4.9 are directed synapses— synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity. This is a common arrangement, but there are also many nondirected synapses in the mammalian nervous sys- tem. Nondirected synapses are synapses at which the site of re- lease is at some distance from the site of reception. One type of nondirected synapse is depicted in Figure 4.10. In this type of arrangement, neurotransmitter molecules are released from a

86 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Microtubules

Synaptic vesicles

Button

Synaptic cleft

Golgi complex

Mitochondrion

Dendritic spine

Presynaptic membrane

Postsynaptic membrane

FIGURE 4.8 The anatomy of a typical synapse.

Simulate Synaptic Transmission www.mypsychlab.com

IS B

N 0-558-78571-9

series of varicosities (bulges or swellings) along the axon and its branches and thus are widely dispersed to surrounding tar- gets. Because of their appear- ance, these synapses are often referred to as string-of-beads synapses.

Synthesis, Packaging, and Transport of Neurotransmitter Molecules

There are two basic categories of neurotransmitter mole- cules: small and large. The small neurotransmitters are of several types; large neuro-

transmitters are all neuropep- tides. Neuropeptides are short amino acid chains comprising between 3 and 36 amino acids; in effect, they are short proteins.

Small-molecule neurotrans- mitters are typically synthesized in the cytoplasm of the terminal button and packaged in synaptic vesicles by the button’s Golgi complex (see Brittle & Waters, 2000). (This may be a good point at which to review the in- ternal structures of neurons in Figure 3.6 on page 56.) Once filled with neurotransmitter, the vesicles are stored in clusters next to the presynaptic membrane. In

contrast, neuropeptides, like other proteins, are assem- bled in the cytoplasm of the cell body on ribosomes; they are then packaged in vesicles by the cell body’s Golgi complex and transported by microtubules to the termi- nal buttons at a rate of about 40 centimeters per day.

874.5 ■ Synaptic Transmission: Chemical Transmission of Signals among Neurons

Presynaptic Facilitation and Inhibition

Axoaxonic synapse

Neuron A synapses on the terminal button of neuron B. Some such axoaxonic synapses increase the effects of one neuron (B) on another (C) (presynaptic facilitation); others decrease the effects of one neuron (B) on another (C) (presynaptic inhibition). The advantage of presynaptic facilitation and inhibition is that they selectively influence single synapses, rather than the entire neuron.

FIGURE 4.9 Presynaptic facilita- tion and inhibition.

Neurotransmitter moleculesVaricosity

FIGURE 4.10 Nondirected neuro- transmitter release. Some neurons release neurotransmitter molecules diffusely from varicosities along the axon and its branches.

Watch Neurotransmitters: Communicators between Neurons www.mypsychlab.com

IS B

N 0-

55 8-

78 57

1- 9

The vesicles that contain neuropeptides are usually larger than those that contain small-molecule neurotransmit- ters, and they do not usually congregate as closely to the presynaptic membrane as the other vesicles do.

It was once believed that each neuron synthesizes and releases only one neurotransmitter, but it has been clear for some time that many neurons contain two neurotransmitters—a situation that is generally referred to as coexistence. It may have escaped your notice that the button illustrated in Figure 4.8 contains synaptic vesicles of two sizes. This suggests that it contains two neurotrans- mitters: a neuropeptide in the larger vesicles and a small- molecule neurotransmitter in the smaller vesicles. So far, most documented cases of coexistence have involved one small-molecule neurotransmitter and one neuropeptide.

Release of Neurotransmitter Molecules

Exocytosis—the process of neurotransmitter release—is illustrated in Figure 4.11 (see Schweizer & Ryan, 2006). When a neuron is at rest, synaptic vesicles that contain small-molecule neurotransmitters tend to congregate near sections of the presynaptic membrane that are par- ticularly rich in voltage-activated calcium channels (see Rizzoli & Betz, 2004, 2005). When stimulated by action potentials, these channels open, and Ca2� ions enter the button. The entry of the Ca2� ions causes synaptic vesi- cles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft (see Collin, Marty, & Llano, 2005; Schneggenburger & Neher, 2005). At many— but not all—synapses, one action potential causes the

88 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Presynaptic membrane

Postsynaptic membrane

FIGURE 4.11 Schematic and photographic illustrations of exocytosis. (The photomicrograph was reproduced from J. E. Heuser et al., Journal of Cell Biology, 1979, 81, 275–300, by copyright permission of The Rockefeller University Press.)

IS B

N 0-558-78571-9

release of neurotransmitter molecules from one vesicle (Matsui & Jahr, 2006).

The exocytosis of small-molecule neurotransmitters differs from the exocytosis of neuropeptides. Small-molecule neurotransmitters are typically released in a pulse each time an action potential triggers a momentary influx of Ca2� ions through the presynaptic membrane; in con- trast, neuropeptides are typically released gradually in re- sponse to general increases in the level of intracellular Ca2� ions, such as might occur during a general increase in the rate of neuron firing.

Activation of Receptors by Neurotransmitter Molecules Once released, neurotrans- mitter molecules produce sig- nals in postsynaptic neurons by binding to receptors in the postsynaptic membrane. Each receptor is a protein that contains binding sites for only particular neurotransmitters; thus, a neurotransmitter can influence only those cells that have receptors for it. Any molecule that binds to another is

referred to as its ligand, and a neurotransmit- ter is thus said to be a ligand of its receptor.

It was initially assumed that there is only one type of receptor for each neurotrans- mitter, but this has not proved to be the case. As more receptors have been identi- fied, it has become clear that most neuro- transmitters bind to several different types of receptors. The different types of recep- tors to which a particular neurotransmitter can bind are called the receptor subtypes for that neurotransmitter. The various re- ceptor subtypes for a neurotransmitter are typically located in different brain areas, and they typically respond to the neuro- transmitter in different ways (see Darlison & Richter, 1999). Thus, one advantage of re- ceptor subtypes is that they enable one neu- rotransmitter to transmit different kinds of messages to different parts of the brain.

The binding of a neurotransmitter to one of its receptor subtypes can influence a post- synaptic neuron in one of two fundamen- tally different ways, depending on whether the receptor is ionotropic or metabotropic (Heuss & Gerber, 2000; Waxham, 1999). Ionotropic receptors are those receptors that are associated with ligand-activated ion channels; metabotropic receptors are those receptors that are associated with signal pro- teins and G proteins (guanosine-triphos- phate–sensitive proteins); see Figure 4.12.

When a neurotransmitter molecule binds to an ionotropic receptor, the associated ion channel usually opens or closes immedi- ately, thereby inducing an immediate post- synaptic potential. For example, in some neurons, EPSPs (depolarizations) occur be- cause the neurotransmitter opens sodium channels, thereby increasing the flow of Na�

894.5 ■ Synaptic Transmission: Chemical Transmission of Signals among Neurons

An Ionotropic Receptor

A Metabotropic Receptor

Some neurotransmitter molecules bind to receptors on membrane signal proteins, which are linked to G proteins. When a neurotransmitter molecule binds to a metabotropic receptor, a subunit of the G protein breaks off into the neuron and either binds to an ion channel or stimulates the synthesis of a second messenger.

Ionotropic receptor

Neurotransmitter

Ion

Closed ion channel

Metabotropic receptor

Signal protein

Neurotransmitter

G Protein

Some neurotransmitter molecules bind to receptors on ion channels. When a neurotransmitter molecule binds to an ionotropic receptor, the channel opens (as in this case) or closes, thereby altering the flow of ions into or out of the neuron.

FIGURE 4.12 Ionotropic and metabotropic receptors.

Watch Synaptic Chemical Messengers www.mypsychlab.com

IS B

N 0-

55 8-

78 57

1- 9

ions into the neuron. In contrast, IPSPs (hyperpolariza- tions) often occur because the neurotransmitter opens potassium channels or chloride channels, thereby increas- ing the flow of K� ions out of the neuron or the flow of Cl� ions into it, respectively.

Metabotropic receptors are more prevalent than ionotropic receptors, and their effects are slower to de- velop, longer-lasting, more diffuse, and more varied. There are many different kinds of metabotropic recep- tors, but each is attached to a serpentine signal protein that winds its way back and forth through the cell mem- brane seven times. The metabotropic receptor is attached to a portion of the signal protein outside the neuron; the G protein is attached to a portion of the signal protein in- side the neuron.

When a neurotransmitter binds to a metabotropic re- ceptor, a subunit of the associated G protein breaks away. Then, one of two things happens, depending on the par- ticular G protein. The subunit may move along the inside surface of the membrane and bind to a nearby ion chan- nel, thereby inducing an EPSP or IPSP; or it may trigger the synthesis of a chemical called a second messenger (neurotransmitters are considered to be the first messen- gers). Once created, a second messenger diffuses through the cytoplasm and may influence the activities of the neu- ron in a variety of ways (Neves, Ram, & Iyengar, 2002)— for example, it may enter the nucleus and bind to the DNA, thereby influencing genetic expression Thus, a neu- rotransmitter’s binding to a metabotropic receptor can have radical, long-lasting effects—see the discussion of epigenetics in Chapter 2.

One type of metabotropic receptor—autoreceptors— warrants special mention. Autoreceptors are metabotropic receptors that have two unconventional characteristics: They bind to their neuron’s own neurotransmitter mole- cules; and they are located on the presynaptic, rather than the postsynaptic, membrane. Their usual function is to monitor the number of neurotransmitter molecules in the synapse, to reduce subsequent release when the levels are high, and to increase subsequent release when they are low.

Differences between small-molecule and peptide neu- rotransmitters in patterns of release and receptor binding suggest that they serve different functions. Small-molecule neurotransmitters tend to be released into directed synapses and to activate either ionotropic receptors or metabotropic receptors that act directly on ion channels. In contrast, neuropeptides tend to be released diffusely, and virtually all bind to metabotropic receptors that act through second messengers. Consequently, the function of small-molecule neurotransmitters appears to be the transmission of rapid, brief excitatory or inhibitory sig- nals to adjacent cells; and the function of neuropeptides appears to be the transmission of slow, diffuse, long-lasting signals.

Reuptake, Enzymatic Degradation, and Recycling If nothing intervened, a neurotransmitter molecule would remain active in the synapse, in effect clogging that channel of communication. However, two mechanisms

90 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Enzymatic Degradation

Deactivating enzyme

Two Mechanisms of Neurotransmitter Deactivation in Synapses

Reuptake

Neurotransmitter molecule

Transporter

FIGURE 4.13 The two mechanisms for terminating neurotransmitter action in the synapse: reuptake and enzymatic degradation.

IS B

N 0-558-78571-9

terminate synaptic messages and keep that from happen- ing. These two message-terminating mechanisms are reuptake by transporters and enzymatic degradation (see Figure 4.13).

Reuptake is the more common of the two deactivating mechanisms. The majority of neurotransmitters, once released, are almost immediately drawn back into the pre- synaptic buttons by transporter mechanisms.

In contrast, other neurotransmitters are degraded (broken apart) in the synapse by the action of enzymes—proteins that stimulate or inhibit biochemi- cal reactions without being affected by them. For exam- ple, acetylcholine, one of the few neurotransmitters for which enzymatic degradation is the main mechanism of synaptic deactivation, is broken down by the enzyme acetylcholinesterase.

Terminal buttons are models of efficiency. Once re- leased, neurotransmitter molecules or their breakdown products are drawn back into the button and recycled, re- gardless of the mechanism of their deactivation. Even the vesicles, once they have done their job, are drawn back into the neuron from the presynaptic membrane and are used to create new vesicles (Südhof, 2004).

Glial Function and Synaptic Transmission Once overlooked as playing merely supportive roles in the nervous system, glial cells have been thrust to center stage

by a wave of remarkable findings. For example, astrocytes have been shown to release chemical transmitters, to con- tain receptors for neurotransmitters, to conduct signals, and to participate in neurotransmitter reuptake (see Fields & Burnstock, 2006; Miller & Cleveland, 2005). Indeed, it is becoming inappropriate to think of brain function solely in terms of neuron–neuron connections. Neurons are only part of the story.

The importance of glial cells in brain function is suggested by the greater prevalence of these cells in intelligent organisms. Will neuroscience prove to be a misnomer? Anybody for “gliascience”?

Gap Junctions Interest in gap junctions has recently been rekindled. Gap junctions are narrow spaces between adjacent neurons that are bridged by fine tubular chan- nels, called connexins, that contain cytoplasm. Conse- quently, the cytoplasm of the two neurons is continuous, allowing electrical signals and small molecules to pass from one neuron to the next (see Figure 4.14). Gap junc- tions are sometimes called electrical synapses.

Gap junctions are commonplace in invertebrate ner- vous systems, but their existence was more difficult to es- tablish in mammals (see Bennett, 2000). They were first demonstrated in mammals in the 1970s, but few mam- malian examples accumulated over the ensuing 30 years. Then technological developments led to the discovery of gap junctions throughout the mammalian brain; they

seem to be an integral feature of local neu- ral inhibitory circuits (Hestrin & Galarreta, 2005). In addition, astrocytes have been shown to communicate with each other, neurons, and other cells through gap junc- tions (Bennett et al., 2003). Thus, the focus on glial function is reviving interest in gap junctions.

The role of gap junctions in nervous system activity is both underappreciated (Conners & Long, 2004) and poorly un- derstood (Nagy, Dudek, & Rash, 2004). Al- though they are less selective than synapses, gap junctions have two advan- tages. One is that communication across them is very fast because it does not in- volve active mechanisms. The other ad- vantage is that gap junctions permit communication in either direction.

914.5 ■ Synaptic Transmission: Chemical Transmission of Signals among Neurons

Evolutiona Evolutionary Perspective Perspective

Prejunction membrane of one cell

Postjunction membrane of other cell

Pores connecting cytoplasm of two cells

Connexins

FIGURE 4.14 Gap junctions. Gap junctions connect the cytoplasm of two cells.

IS B

N 0-

55 8-

78 57

1- 9

4.6 Neurotransmitters

Now that you understand the basics of neurotransmitter function, let’s take a closer look at some of the well over 100 neurotransmitter substances that have been identi- fied (see Purves et al., 2004). The following are three classes of conventional small-molecule neurotransmit- ters: the amino acids, the monoamines, and acetylcholine. Also, there is a fourth group of various small-molecule neurotransmitters, which are often referred to as unconventional neurotransmitters because their mecha- nisms of action are unusual. In contrast to the small- molecule neurotransmitters, there is only one class of large-molecule neurotransmitters: the neuropeptides. Most neurotransmitters produce either excitation or inhi- bition, not both; but a few produce excitation when they

bind to some of their receptor subtypes and inhibition when they bind to others. All of the neurotransmitter classes and individual neurotransmitters that appear in this section in boldface type are presented in Figure 4.17 at the end of this section.

Amino Acid Neurotransmitters The neurotransmitters in the vast majority of fast-acting, directed synapses in the central nervous system are amino acids—the molecular building blocks of proteins. The four most widely studied amino acid neurotransmitters are glutamate, aspartate, glycine, and gamma-aminobutyric acid (GABA). The first three are common in the proteins we consume, whereas GABA is synthesized by a simple modification of the structure of glutamate. Glutamate is the most prevalent excitatory neurotransmitter in the mammalian central nervous system. GABA is the most prevalent inhibitory neurotransmitter (see Jacob, Moss, & Jurd, 2008; Orser, 2007); however, it has excitatory effects at some synapses (Szabadics et al., 2006).

Monoamine Neurotransmitters Monoamines are another class of small-molecule neuro- transmitters. Each is synthesized from a single amino acid—hence the name monoamine (one amine). Monoamine neurotransmitters are slightly larger than amino acid neurotransmitters, and their effects tend to be more diffuse (see Bunin & Wightman, 1999). The monoamines are present in small groups of neurons whose cell bodies are, for the most part, located in the brain stem. These neurons often have highly branched axons with many varicosities (string-of-beads synapses), from which monoamine neurotransmitters are dif- fusely released into the extracellular fluid (see Figures 4.10 and 4.15).

There are four monoamine neurotransmitters: dopamine, epinephrine, norepinephrine, and serotonin. They are subdivided into two groups, catecholamines and indolamines, on the basis of their structures. Dopamine, norepinephrine, and epinephrine are catecholamines. Each is synthesized from the amino acid tyrosine. Tyrosine is con- verted to L-dopa, which in turn is converted to dopamine. Neurons that release norepinephrine have an extra enzyme (one that is not present in dopaminergic neurons), which converts the dopamine in them to norepinephrine. Simi- larly, neurons that release epinephrine have all the enzymes present in neurons that release norepinephrine, along with an extra enzyme that converts norepinephrine to epineph- rine (see Figure 4.16). In contrast to the other monoamines, serotonin (also called 5-hydroxytryptamine, or 5-HT) is syn- thesized from the amino acid tryptophan and is classified as an indolamine.

Neurons that release norepinephrine are called noradrenergic; those that release epinephrine are called

92 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Before moving on to the discussion of specific neurotrans- mitters, review the general principles of axon conduction and synaptic transmission. Draw a line to connect each term in the left column with the appropriate word or phrase in the right column. The correct answers are pro- vided at the end of the exercise. Before proceeding, review material related to your errors and omissions.

a. axonal conduction of action potentials

b. orthodromic c. myelin d. nodes of Ranvier e. multiple f. dendritic

g. compartmentalize dendrites

h. somas i. axoaxonic synapses j. string-of-beads

k. neuropeptides l. store neurotransmitters

m. G proteins n. enzymatic degradation o. gap junctions

1. fatty 2. sclerosis 3. cell bodies 4. dendritic spines 5. nondecremental 6. presynaptic facilitation 7. nondirected synapses 8. synaptic vesicles 9. from cell body to

terminal buttons 10. acetylcholinesterase 11. short amino acid chains 12. saltatory 13. metabotropic receptors 14. electrical synapses 15. spines

Scan Your Brainanswers: (1) c, (2) e, (3) h, (4) g, (5) a, (6) i, (7) j, (8) l, (9) b, (10) n, (11) k, (12) d, (13) m, (14) o, (15) f.

IS B

N 0-558-78571-9

adrenergic. There are two reasons for this naming. One is that epinephrine and norepinephrine used to be called adrenaline and noradrenaline, respectively, by many scien- tists, until a drug company registered Adrenalin as a brand name. The other reason will become apparent to you if you try to say norepinephrinergic.

Acetylcholine Acetylcholine (abbreviated Ach) is a small-molecule neu- rotransmitter that is in one major respect like a professor who is late for a lecture: It is in a class by itself. It is cre- ated by adding an acetyl group to a choline molecule. Acetylcholine is the neurotransmitter at neuromuscular junctions, at many of the synapses in the autonomic nerv- ous system, and at synapses in several parts of the central nervous system. As you learned in the last section, acetyl- choline is broken down in the synapse by the enzyme acetylcholinesterase. Neurons that release acetylcholine are said to be cholinergic.

Unconventional Neurotransmitters The unconventional neurotransmitters act in ways that are different from those that neuroscientists have come to think of as typical for such substances. One class of unconventional neurotransmitters, the soluble-gas neurotransmitters, includes nitric oxide and carbon monoxide (Boehning & Snyder, 2003). These neuro- transmitters are produced in the neural cytoplasm and immediately diffuse through the cell membrane into the extracellular fluid and then into nearby cells. They eas- ily pass through cell membranes because they are solu- ble in lipids. Once inside another cell, they stimulate the production of a second messenger and in a few seconds are deactivated by being converted to other molecules. They are difficult to study because they exist for only a few seconds.

Soluble-gas neurotransmitters have been shown to be involved in retrograde transmission. At some synapses, they transmit feedback signals from the post- synaptic neuron back to the presynaptic neuron. The function of retrograde transmission seems to be to reg- ulate the activity of presynaptic neurons (Ludwig & Pittman, 2003).

Another class of unconventional neurotransmitters, the endocannabinoids, has only recently been discov- ered. Endocannabinoids are neurotransmitters that are

934.6 ■ Neurotransmitters

FIGURE 4.15 String-of-beads noradrenergic nerve fibers. The bright, beaded structures represent sites in these multiple- branched axons where the monoamine neurotransmitter nor- epinephrine is stored in high concentration and released into the surrounding extracellular fluid. (Courtesy of Floyd E. Bloom, M.D., The Scripps Research Institute, La Jolla, California.)

Epinephrine

Norepinephrine

Dopamine

L-dopa

Tyrosine

FIGURE 4.16 The steps in the synthesis of catecholamines from tyrosine.

IS B

N 0-

55 8-

78 57

1- 9

similar to delta-9-tetrahydrocannabinol (THC), the main psychoactive (producing psychological effects) constituent of marijuana (see Chapter 15). So far, two endocannabi- noids have been discovered (Van Sickle et al., 2005). The most widely studied is anandamide (from the Sanskrit word ananda, which means “eternal bliss”). Like the solu- ble gases, the endocannabinoids are produced immedi- ately before they are released. Endocannabinoids are synthesized from fatty compounds in the cell membrane; they tend to be released from the dendrites and cell body; and they tend to have most of their effects on presynaptic neurons, inhibiting subsequent synaptic transmission (see Glickfield & Scanziani, 2005).

Neuropeptides Over 100 neuropeptides have been identified (see Ludwig & Leng, 2006). The actions of each neuropeptide depend on its amino acid sequence.

It is usual to loosely group neuropeptide transmitters into five categories. Three of these categories acknowl- edge that neuropeptides often function in multiple capac- ities, not just as neurotransmitters: One category (pituitary peptides) contains neuropeptides that were first identified as hormones released by the pituitary; a second category (hypothalamic peptides) contains neu- ropeptides that were first identified as hormones released by the hypothalamus; and a third category (brain–gut peptides) contains neuropeptides that were first discov- ered in the gut. The fourth cate- gory (opioid peptides) contains neuropeptides that are similar in structure to the active ingredients of opium, and the fifth (miscellaneous peptides) is a catch-all category that contains all of the neuropeptide transmit- ters that do not fit into one of the other four categories.

Figure 4.17 summarizes all the neurotransmitters that were in- troduced in this section. If it has not already occurred to you, this table should be very useful for re- viewing the material.

94 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Acetylcholine

Dopamine Epinephrine Norepinephrine

Glutamate Aspartate Glycine GABA

Monoamines

SerotoninIndolamines

Catecholamines

Acetylcholine

Nitric oxide Carbon monoxideUnconventional

neurotransmitters

Amino acids

Soluble gases

Endocannabinoids Anandamide

Small-Molecule Neurotransmitters

Pituitary peptides Hypothalamic peptides Brain–gut peptides Opioid peptides Miscellaneous peptides

Neuropeptides

Large-Molecule Neurotransmitters

FIGURE 4.17 Classes of neuro- transmitters and the particular neuro- transmitters that were discussed (and appeared in boldface) in this section.

This is a good place for you to pause to scan your brain to see if you are ready to proceed. Are you familiar with the neurotransmitters to which you have just been intro- duced? Find out by filling in the blanks. The correct an- swers are provided at the end of the exercise. Before proceeding, review material related to your errors and omissions.

Amino acids are the neurotransmitters in the vast majority of (1) ______ acting, directed synapses. Four amino acids are widely recognized neurotransmitters: (2) ______, (3) ______, (4) ______, and (5) ______. In contrast to the amino acid neurotransmitters, the (6) ______ are small-molecule neurotransmitters with slower, more diffuse effects; they belong to one of two categories: (7) ______ or indolamines. In the former category are epinephrine, (8) ______, and (9) ______; (10) ______ is the only neurotransmitter in the latter category. (11) ______, the neurotransmitter at neuro- muscular junctions, is a neurotransmitter in a class by itself. There are also unconventional neurotransmitters: the (12) ______ neurotransmitters, such as nitric oxide

IS B

N 0-558-78571-9

4.7 Pharmacology of Synaptic Transmission and Behavior

In case you have forgotten, the reason I have asked you to invest so much effort in learning about the neurotrans- mitters is that they play a key role in how the brain works. We began this chapter on a behavioral note by considering the pathological behavior of Roberto Garcia d’Orta, which resulted from a Parkinson’s disease–related disruption of his dopamine function. Now, let’s return to behavior.

Most of the methods that biopsychologists use to study the behavioral effects of neurotransmitters are pharmacological (involving drugs). To study neurotrans- mitters and behavior, researchers administer to human or nonhuman subjects drugs that have particular effects on particular neurotransmitters and then assess the effects of the drugs on behavior.

Drugs have two fundamentally different kinds of ef- fects on synaptic transmission: They facilitate it or they inhibit it. Drugs that facilitate the effects of a particular neurotransmitter are said to be agonists of that neuro-

transmitter. Drugs that inhibit the effects of a particular neu- rotransmitter are said to be its antagonists.

How Drugs Influence Synaptic Transmission Although synthesis, release, and action vary from neuro- transmitter to neurotransmitter, the following seven general steps are common to most neurotransmitters: (1) synthesis of the neurotransmitter, (2) storage in vesicles, (3) break- down in the cytoplasm of any neurotransmitter that leaks from the vesicles, (4) exocytosis, (5) inhibitory feedback via autoreceptors, (6) activation of postsynaptic receptors, and (7) deactivation. Figure 4.18 on page 96 illustrates these seven steps, and Figure 4.19 on page 97 illustrates some ways that agonistic and antagonistic drugs influence them.

For example, some agonists of a particular neurotransmitter bind to postsynaptic receptors and activate them, whereas some antagonistic drugs, called receptor blockers, bind to postsynaptic receptors without activating them and, in so doing, block the access of the usual neurotransmitter.

Behavioral Pharmacology: Three Influential Lines of Research You will encounter discussions of the putative (hypothet- ical) behavioral functions of various neurotransmitters in subsequent chapters. However, this chapter ends with de- scriptions of three particularly influential lines of research on neurotransmitters and behavior. Each line of research led to the discovery of an important principle of neuro- transmitter function, and each illustrates how drugs are used to study the nervous system and behavior.

Wrinkles and Darts: Discovery of Receptor Subtypes It was originally assumed that there was one kind of receptor for each neurotransmitter, but this notion was dispelled by research on acetylcholine receptors (see Changeux & Edelstein, 2005). Some acetylcholine receptors bind to nicotine (a CNS stimulant and major psychoactive ingredient of tobacco), whereas other acetylcholine recep- tors bind to muscarine (a poisonous substance found in some mushrooms). These two kinds of acetylcholine receptors thus became known as nicotinic receptors and muscarinic receptors.

Next, it was discovered that nicotinic and muscarinic receptors are distributed differently in the nervous sys- tem, have different modes of action, and consequently have different behavioral effects. Both nicotinic and mus- carinic receptors are found in the CNS and the PNS. In the PNS, many nicotinic receptors occur at the junctions between motor neurons and muscle fibers, whereas many muscarinic receptors are located in the autonomic nerv- ous system (ANS). Nicotinic and muscarinic receptors are ionotropic and metabotropic, respectively.

Many of the drugs that are used in research and in medicine are extracts of plants that have long been used for medicinal and recreational purposes. The cholinergic agonists and antagonists illustrate this point well. For ex- ample, the ancient Greeks consumed extracts of the bel- ladonna plant to treat stomach ailments and to make themselves more attractive. Greek women believed that the pupil-dilating effects of these extracts enhanced their beauty (belladonna means “beautiful lady”). Atropine, which is the main active ingredient of belladonna, is a re- ceptor blocker that exerts its antagonist effect by binding to muscarinic receptors, thereby blocking the effects of acetylcholine on them. The pupil-dilating effects of at- ropine are mediated by its antagonist actions on mus- carinic receptors in the ANS. In contrast, the disruptive effects of large doses of atropine on memory is mediated by its antagonistic effect on muscarinic receptors in the

954.7 ■ Pharmacology of Synaptic Transmission and Behavior

Scan Your Brainanswers: (1) fast, (2, 3, 4, 5) glutamate, aspartate, glycine, and GABA, in any order, (6) monoamines, (7) catecholamines, (8, 9) norepinephrine and dopamine, in either order, (10) serotonin, (11) Acetylcholine, (12) soluble-gas, (13) amino acids, (14) opioid.

and carbon monoxide, and the endocannabinoids. Finally, the neuropeptides, which are short chains of (13) ______, are the only large-molecule neurotrans- mitters. They are usually grouped into five categories: the pituitary peptides, the hypothalamic peptides, the brain–gut peptides, the (14) ______ peptides, and the miscellaneous peptides.

Simulate Psychoactive Drugs www.mypsychlab.com

IS B

N 0-

55 8-

78 57

1- 9

CNS. The disruptive effect of high doses of atropine on memory was one of the earliest clues that cholinergic mechanisms may play a role in memory (see Chapter 11).

South American natives have long used curare—an ex- tract of a certain class of woody vines—on the tips of darts they use to kill their game and occasionally their enemies. Like atropine, curare is a receptor blocker at cholinergic synapses, but it acts at nicotinic receptors. By binding to nicotinic receptors, curare blocks transmission at neuromuscular junctions, thus paralyzing its recipients and killing them by blocking their respiration. You may be surprised, then, to learn that the active ingredient of curare

is sometimes administered to human pa- tients during surgery to ensure that their muscles do not contract during an inci- sion. When curare is used for this purpose, the patient’s breathing must be artificially maintained by a respirator.

Botox (short for Botulinium toxin), a neurotoxin re- leased by a bacterium often found in spoiled food, is another nicotinic antagonist, but its mechanism of action is different: It blocks the release of acetylcholine at neu- romuscular junctions and is thus a deadly poison. However, injected in minute doses at specific sites, it has applications

96 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Seven Steps in Neurotransmitter Action

Neurotransmitter molecules are synthesized

from precursors under the influence of enzymes.

Neurotransmitter molecules are

stored in vesicles.

Neurotransmitter molecules that leak

from their vesicles are destroyed by enzymes.

Action potentials cause vesicles to fuse with the

presynaptic membrane and release their neurotransmitter molecules into the synapse.

Released neurotransmitter molecules bind with

autoreceptors and inhibit subsequent neurotransmitter release.

Released neurotransmitter molecules are deactivated

by either reuptake or enzymatic degradation.

Released neurotransmitter molecules bind to postsynaptic

receptors.

Synthesizing enzymes

Neurotransmitter precursors

Degrading enzymes

Vesicle

Autoreceptor

Postsynaptic receptor

FIGURE 4.18 Seven steps in neurotransmitter action: (1) synthesis, (2) storage in vesicles, (3) breakdown of any neurotransmitter leaking from the vesicles, (4) exocytosis, (5) inhibitory feedback via autoreceptors, (6) activation of postsynaptic receptors, and (7) deactivation.

Clinical Clinical Implications Implications

IS B

N 0-558-78571-9

in medicine (e.g., reduction of tremors) and cosmetics (e.g., reduction of wrinkles; see Figure 4.20 on page 98).

Pleasure and Pain: Discovery of Endogenous Opioids Opium, the sticky resin obtained from the seed pods of the opium poppy, has been used by humans since prehis- toric times for its pleasurable effects. Morphine, its major psychoactive ingredient, is highly addictive. But mor- phine also has its good side: It is an effective analgesic (painkiller)—see Chapters 7 and 15.

In the 1970s, it was discovered that opiate drugs such as morphine bind effectively to receptors in the brain. These receptors were generally found in the hypothalamus and other limbic areas, but they were most concentrated in the area of the brain stem around the cerebral aqueduct, which connects the third and fourth ventricles; this part of the

brain stem is called the periaqueductal gray (PAG). Microinjection of mor- phine into the PAG, or even electrical

stimulation of the PAG, produces strong analgesia.

The existence of selective opiate receptors in the brain raised an interesting question: Why are they there? They are certainly not there so that once humans discovered opium, opiates would have a place to bind. The existence of opiate receptors suggested that opioid (opiate-like) chemicals occur naturally in the brain, and that possibil- ity triggered an intensive search for them.

Several families of endogenous (occurring naturally within the body) opioids have been discovered. First discov- ered were the enkephalins (meaning “in the head”). An- other major family of endogenous opioids are the endorphins (a contraction of “endogenous morphine”). All endogenous opioid neurotransmitters are neuropeptides, and their receptors are metabotropic.

Tremors and Insanity: Discovery of Antischizo- phrenic Drugs Arguably, the most important event in the treatment of mental illness has been the development of drugs for the treatment of schizophrenia (see Chapter 18). Surprisingly, Parkinson’s disease, the disease from which

974.7 ■ Pharmacology of Synaptic Transmission and Behavior

Drug increases the synthesis of neurotransmitter molecules (e.g., by increasing the amount of precursor).

Drug increases the number of neurotransmitter molecules by destroying degrading enzymes.

Drug increases the release of neurotransmitter molecules from terminal buttons.

Drug binds to autoreceptors and blocks their inhibitory effect on neurotransmitter release.

Drug binds to postsynaptic receptors and either activates them or increases the effect on them of neurotransmitter

Drug blocks the deactivation of neurotransmitter molecules by blocking degradation or reuptake.

Drug blocks the synthesis of neurotransmitter molecules (e.g., by destroying synthesizing enzymes).

Drug causes the neurotransmitter molecules to leak from the vesicles and be destroyed by degrading enzymes.

Drug blocks the release of the neurotransmitter molecules from terminal buttons.

Drug activates autoreceptors and inhibits neurotransmitter release.

Drug is a receptor blocker; it binds to the postsynaptic receptors and blocks the effect of the neurotransmitter.

Some Mechanisms of Drug Action

Agonistic Drug Effects Antagonistic Drug Effects

FIGURE 4.19 Some mechanisms of agonistic and antagonistic drug effects.

Clinical Clinical Implications Implications

IS B

N 0-

55 8-

78 57

1- 9

Roberto Garcia d’Orta suffered, played a major role in their discovery.

In the 1950s, largely by chance, two drugs were found to have antischizophrenic effects. Although these two drugs were not related structurally, they both produced a curious pattern of ef- fects: Neither drug appeared to have any antischizophrenic activity until patients had been taking it for about 3 weeks, at which point the drug also started to produce mild Parkinsonian symptoms (e.g., tremor-at- rest). Researchers put this result together with two then- recent findings: (1) that Parkinson’s disease is associated with the degeneration of the main dopamine pathway of the brain, and (2) that dopamine agonists—cocaine and amphetamines—produce a temporary disorder that re- sembles schizophrenia. Together, these findings suggested that schizophrenia is caused by excessive activity at dopamine synapses, and thus that potent dopamine antag- onists would be effective in its treatment.

It was ultimately discovered that one particular dopamine receptor, the D2 receptor, plays a key role in schizophrenia and that drugs that most effectively block it are the most effective antischizophrenic drugs.

It would be a mistake to think that antischizophrenic drugs cure schizophrenia or that they help in every case. However, they help many patients, and the help is some- times enough to render hospitalization unnecessary. You will learn much more about this important line of re- search in Chapter 18.

98 Chapter 4 ■ Neural Conduction and Synaptic Transmission

FIGURE 4.20 A woman receiving cosmetic Botox injections.

Clinical Implications

Themes Revisited

The function of the nervous system, like the function of any circuit, depends on how signals travel through it. The primary purpose of this chapter was to introduce you to neural conduction and synaptic transmission. This introduction touched on three of the book’s four main themes.

The clinical implications theme was illustrated by the opening case of the Lizard, Roberto Garcia d’Orta. Then, this theme was picked up again at the end of the chapter

during discussions of curare, Botox, endogenous opioids, and antischizophrenic drugs.

The evolutionary perspective theme was implicit through- out the entire chapter, because almost all neurophysiological

research is conducted on the neurons and synapses of nonhuman subjects. However, the evolutionary perspective received explicit emphasis when the particularly high glial-cell-to-neuron ratio of the human brain was noted.

The thinking creatively theme arose in two metaphors: the firing-gun metaphor of action potentials and the mouse- traps-on-a-wobbly-shelf metaphor of axonal conduction. Metaphors are useful in teaching, and scientists find them useful for thinking about the phenomena they study. The text also described the creative Nobel-Prize–winning research of Hodgkin and Huxley on the ionic bases of resting membrane potentials.

Clinical Clinical Implications Implications

Evolutiona Evolutionary Perspective Perspective

Thinking CreativelyThinking Creatively

IS B

N 0-558-78571-9

99Key Terms

Think about It

1. Just as computers operate on binary (yes-no) signals, the all-or-none action potential is the basis of neural com- munication. The human brain is thus nothing more than a particularly complex computer. Discuss.

2. How have the findings described in this chapter changed your understanding of brain function?

3. Why is it important for biopsychologists to understand neural conduction and synaptic transmission? Is it impor- tant for all psychologists to have such knowledge? Discuss.

4. The discovery that neurotransmitters can act directly on DNA via G proteins uncovered a mechanism through which experience and genes can interact (see Chapter 2). Discuss.

5. Dendrites and glial cells are currently “hot” subjects of neuroscientific research. Describe the findings that have generated such interest, and explain how they have changed our conception of brain function.

4.1 Resting Membrane Potential Membrane potential (p. 76) Microelectrodes (p. 76) Resting potential (p. 77) Ions (p. 77) Ion channels (p. 77) Sodium–potassium pumps

(p. 79) Transporters (p. 79)

4.2 Generation and Conduction of Postsynaptic Potentials Depolarize (p. 79) Hyperpolarize (p. 79) Excitatory postsynaptic

potentials (EPSPs) (p. 79) Inhibitory postsynaptic

potentials (IPSPs) (p. 79) Graded responses (p. 79)

4.3 Integration of Postsynaptic Potentials and Generation of Action Potentials Axon hillock (p. 80) Threshold of excitation (p. 80) Action potential (AP) (p. 80)

All-or-none responses (p. 80) Integration (p. 80) Spatial summation (p. 80) Temporal summation (p. 80)

4.4 Conduction of Action Potentials Voltage-activated ion channels

(p. 82) Absolute refractory period

(p. 83) Relative refractory period

(p. 83) Antidromic conduction (p. 84) Orthodromic conduction

(p. 84) Nodes of Ranvier (p. 84) Saltatory conduction (p. 85)

4.5 Synaptic Transmission: Chemical Transmission of Signals among Neurons Dendritic spines (p. 86) Directed synapses (p. 86) Nondirected synapses (p. 86) Neuropeptides (p. 87) Synaptic vesicles (p. 87) Golgi complex (p. 87) Coexistence (p. 88)

Exocytosis (p. 88) Receptors (p. 89) Ligand (p. 89) Receptor subtypes (p. 89) Ionotropic receptors (p. 89) Metabotropic receptors (p. 89) G proteins (p. 89) Second messenger (p. 90) Autoreceptors (p. 90) Reuptake (p. 91) Enzymatic degradation (p. 91) Enzymes (p. 91) Acetylcholinesterase (p. 91) Gap junctions (p. 91)

4.6 Neurotransmitters Amino acid neurotransmitters

(p. 92) Glutamate (p. 92) Aspartate (p. 92) Glycine (p. 92) Gamma-aminobutyric acid

(GABA) (p. 92) Monoamine neurotransmitters

(p. 92) Dopamine (p. 92) Epinephrine (p. 92) Norepinephrine (p. 92) Serotonin (p. 92) Catecholamines (p. 92)

Indolamines (p. 92) Acetylcholine (p. 93) Soluble-gas neurotransmitters

(p. 93) Nitric oxide (p. 93) Carbon monoxide (p. 93) Endocannabinoids (p. 93) Anandamide (p. 94) Neuropeptide transmitters

(p. 94) Pituitary peptides (p. 94) Hypothalamic peptides (p. 94) Brain–gut peptides (p. 94) Opioid peptides (p. 94) Miscellaneous peptides (p. 94)

4.7 Pharmacology of Synaptic Transmission and Behavior Agonists (p. 95) Antagonists (p. 95) Receptor blockers (p. 95) Atropine (p. 95) Botox (p. 96) Periaqueductal gray (PAG)

(p. 97) Endogenous (p. 97) Enkephalins (p. 97) Endorphins (p. 97)

Key Terms

IS B

N 0-

55 8-

78 57

1- 9

100 Chapter 4 ■ Neural Conduction and Synaptic Transmission

Test your comprehension of the chapter with this brief practice test. You can find the answers to these questions as well as more practice tests, activities, and other study resources at www.mypsychlab.com.

1. IPSPs are a. Inhibitory. b. graded. c. all-or-none. d. all of the above e. both a and b

2. Which of the following ions triggers exocytosis by its influx into terminal buttons? a. Cl� b. Ca2� c. glutamate d. glycine e. Na�

3. Which of the following is the most common mechanism of deactivating neurotransmitter molecules in synapses? a. enzymatic degradation b. acetylcholinesterase c. reuptake by transporters d. all of the above e. both a and b

4. All of the following are monoamine neurotransmitters except a. epinephrine. b. serotonin. c. norepinephrine. d. dopamine. e. acetylcholine.

5. Botox is a a. nicotinic agonist b. nicotinic antagonist. c. cholinergic agonist. d. cholinergic antagonist. e. poison used by some South American natives on

their darts.

Quick Review

IS B

N 0-558-78571-9