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Unformatted text preview: 76 Chapter 4 I Neural Conduction and Synaptic Transmission hapter 3 introduced you to the anatomy of neurons. This chapter introduces you to their function—how neurons 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. (Adapted from NEWTON’S MADNESS by Harold Klawans (Harper 8( Row 1990). Reprinted by permission of Jet Literary Associates, Inc.) 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. IE.— 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 time 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 diameterhmuch 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 net is C: witl neu 1.8 f 4.1 I Resting Membrane Potential 77 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 1 ions (KJr ), chloride ions (Cl ), and various negativel _. charged protein ions. The concentrations of both Na+ . Cl’ ions are greater outside a resting neuron than ’ whereas K+ ions are more concentrated on the ' The negatively charged protein ions are synthesize ' the neuron and, for the most part, stay there (0 \d be “ire t anon gra‘ «i ction is reviving interest ,. , s. ”muof gap junctions in nervous i'ty is both underappreciated Long, 2004) and poorly un- gy, Dudek, & Rash, 2004). Al— . Y ' 4.1). By the way, the symbols for sodium an w t e'n' Co s tic charge 7 . are . lessh selectlve dthan were derived from their Latin names. natriilb"e o \ated acct“? manual ) Junctions ave “7° a van- kalium (K) respectively ‘ mtg calcu 3‘ resilflg 9 new” that commumcation across fast because it does not in- lechanisms. The other ad- . at gap junctions permit mmunication in either direction. a: he ac he“ Two properties of the neural membranr same as ‘ eluded that W for the unequal distribution of Na+, K1” uxXeY thus con ions in resting neurons One of these 1' that is, it does not involve the consur other is active and does involve ti, ergy. The passive property of the contributes to the unequal dispos and protein ions is its differential ions. In resting neurons, K+ and 1 through the neural membrane, Na ‘ with difficulty, and the negatively c , not pass through it at all. Ions p I membrane at specialized pores call o: a; 7; fl ‘2 u Er. FIGURE 4.14 Gap junctions. Gap junctions connect the cytoplasm of two cells. I 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: natriurn (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, KJr 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 4.1 I Resting Membrane Potential 77 FIGURE 4.1 |n its resting state, more Na+ and 0- ions are outside the neuron than inside, and more Kt ions and negatively charged protein ions are inside the neuron than outside. type of which is specialized for the passage of particular ions. In the 19505, 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 78 Chapter 4 I 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 C1’ 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 K4r 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 NaJr ions from moving down their concentration gradient into the neuron, which is added to the 70 mV of electrostatic pressure Sodium- potassium pump 90 mV of pressure from concentration gradient 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‘r 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. 70 mV of pressure from concentration ‘radient 50 mV of pressure from concentration gradient FIGURE 4.2 The passive and active factors that influence the distribution of Na+, Kt, and Cl’ ions across the neural membrane. Passive factors continuously drive Kt ions out of the resting neuron and Na+ ions in; therefore, Kt ions must be actively pumped in and NaJr ions must be actively pumped out to maintain the resting equilibrium. —-nrn——_._4 HLJI't-In carnal-rm It was subsequently discovered that the transport of Na+ ions out of neurons and the transport of K4r 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 8r 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 TABLE 4.1 Factors Responsible for Maintaining the Differences in the Intracellular and Extracellular Concentrations of Na+, W, 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. Kt 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 K4r 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, 0‘ 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 CI’ 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. 4,2 I Generation and Conduction of Postsynaptic Potentials 79 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. [El— 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 ...
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