p CHAPTER 5 How Do Neurons Communicate? A Chemical Message Neurotransmitter Systems The Structure of Synapses Neurotransmission in the Skeletal Motor System Focus on Disorders: Parkinson’s Disease Neurotransmission in the Autonomic Nervous Stages in Neurotransmitter Function System Types of Synapses Neurotransmission in the Central Nervous System The Evolution of a Complex Neural Focus on Disorders: The Case of the Frozen Transmission System Addict Excitatory and Inhibitory Messages The Role of Synapses in Learning The Kinds of Neurotransmitters and Memory Identifying Neurotransmitters Learning and Changes in Neurotransmitter Neurotransmitter Classification Release The Types of Receptors for Neurotransmitters Synaptic Change with Learning in the Focus on Disorders: Awakening with L-Dopa Mammalian Brain Long-Term Learning and Associative Learning Learning and the Formation or Loss of Synapses Patrisha Thomson/Stone Micrograph: Dr. Dennis Kunkel/Phototake 152 I p he sea bird called the puffin (genus Fratercula, the puffin’s body, imposes greater resistance to movement which is Latin for “little brother”) exhibits remark- than air does. T able behavior during its breeding season. It digs a To meet its nutrient and oxygen needs during its vari- burrow as deep as 4 feet into the earth, in which to lay its ous behaviors, the puffin’s heart rate changes to match its single egg. While on the ground, the puffin is relatively energy expenditure. The heart beats slowly on land and in- inactive, sitting on its egg or in front of its burrow. But, creases greatly in flight. When the puffin dives beneath the after the egg hatches, the puffin begins a period of Her- surface of the water, however, its heart stops beating. This culean labors. It must fly constantly back and forth response is called diving bradycardia (brady meaning between its burrow and its fishing ground to feed its rav- “slow”; cardia meaning “heart”). Bradycardia is a strategy enous young. It fishes by diving underwater and pro- for conserving oxygen under water, because the circulatory pelling itself by flapping its short stubby wings as if it system expends no energy when the heart ceases pumping. were flying. One by one it catches as many as 30 small Your heart rate varies in the same way as the puffin’s fish, all of which it holds in its beak to be carried back to to meet your energy needs, slowing when you are at rest its chick (Figure 5-1). The chick may eat as many as 2000 and increasing when you are active. Even exciting or re- fish in its first 40 days of life. When flying to its fishing laxing thoughts can cause your heart to increase or de- ground, the puffin exerts a great deal of effort to maintain crease its rate of beating. And, yes, like the puffin and all its momentum. It also expends much energy as it “flies” other diving animals, when you submerge your head in through the water, because the water, although it supports water, you, too, display diving bradycardia. What regulates all this turning up, down, and off of heart- beat as behavior requires? Because the heart has no knowledge Kevin Schafer about how quickly it should beat, it must be told to adjust its rate of beating. These com- mands consist of at least two different mes- sages: an excitatory message that says “speed up” and an inhibitory message that says “slow down.” What is important to our understanding of how neurons interact is that it was an experiment designed to study how heart rate is controlled that yielded an answer to the question of how neurons com- municate with one another. In this chapter, we explore that answer in some detail. First, Figure 5-1 we consider the chemical signals that neurons use to in- A puffin is returning with food for its chick. Its heart rate varies to hibit or excite each other. Then, we examine the function match its energy needs, slowing down on land, increasing during of excitatory and inhibitory synapses and excitatory and flight, and stopping completely when the puffin dives below the surface of the water to fish. inhibitory receptors. Finally, we investigate the changes that synapses undergo during learning. I 153 154 I CHAPTER 5 A CHEMICAL MESSAGE In 1921, Otto Loewi conducted a now well-known experiment on the control of heart rate, the design of which came to him in a dream. One night, having fallen asleep while reading a short novel, he awoke suddenly and completely, with the idea fully formed. He scribbled the plan of the experiment on a scrap of paper and went back to sleep. The next morning, he could not decipher what he had written, yet he felt it was impor- tant. All day he went about in a distracted manner, looking occasionally at his notes, but wholly mystified about their meaning. That night he again awoke, vividly recalling Otto Loewi (1873–1961) the ideas in his previous night’s dream. Fortunately, he still remembered them the next morning. Loewi immediately set up and successfully performed the experiment. Loewi’s experiment involved electrically stimulating a frog’s vagus nerve, which leads from the brain to the heart, while at the same time channeling the fluid in which the stim- ulated heart had been immersed to a second heart that was not electrically stimulated, as shown in Figure 5-2. The fluid traveled from one container to the other through a tube. Loewi recorded the rate of beating of both hearts. The electrical stimulation decreased the rate of beating of the first heart, but, more important, the fluid transferred from the first to the second container slowed the rate of beating of the second heart, too. Clearly, a mes- sage about the speed at which to beat was somehow carried in the fluid. But where did the message originally come from? The only way in which it could have gotten into the fluid was by a chemical released from the vagus nerve. This chemical must have dissolved into the fluid in sufficient quantity to influence the sec- ond heart. The experiment therefore demonstrated that the vagus nerve contains a EXPERIMENT Question: How does a neuron pass on a message? Stimulating Recording device device 1 2 Vagus nerve of frog Fluid is transferred heart 1 is stimulated. from first to second container. Figure 5-2 Otto Loewi’s 1921 experiment Vagus demonstrating the involvement of a nerve neurochemical in controlling heart rate. He electronically stimulated the vagus Fluid transfer nerve going to a frog heart that was maintained in a salt bath. The heart decreased its rate of beating. Fluid from the bath was transferred to a second Frog heart 1 Frog heart 2 bath containing a second heart. The Rate of electrical recording from the second heartbeats heart shows that its rate of beating also decreased. This experiment demonstrates that a chemical released from the vagus Stimulation nerve of the first heart can reduce the 3 4 Conclusion rate of beating of the second heart. Recording from frog heart …as does the recording The message is a Follow the main steps in the experiment 1 shows decreased rate of from frog heart 2 after chemical released to arrive at the conclusion that beating after stimulation… the fluid transfer. by the nerve. neurotransmission is chemical. p HOW DO NEURONS COMMUNICATE? I 155 chemical that tells the heart to slow its rate of beating. Loewi subsequently identified that chemical as acetylcholine (ACh). In further experiments, Loewi stimulated another nerve, called the accelerator nerve, and obtained a speeding-up of heart rate. Moreover, the fluid that bathed the accelerated heart increased the rate of beating of a second heart that was not electri- cally stimulated. Loewi identified the chemical that carried the message to speed up heart rate as epinephrine (EP). Together, these complementary experiments showed that chemicals from the vagus nerve and the accelerator nerve modulate heart rate, with one inhibiting the heart and the other exciting it. Acetylcholine (ACh) Epinephrine (EP) Chemicals that are released by a neuron onto a target are now referred to as chemical neurotransmitters. Neurons that contain a chemical neurotransmitter of a certain type are named after that neurotransmitter. For example, neurons with terminals that release ACh are called acetylcholine neurons, whereas neurons that release EP are called epi- Figure 5-3 nephrine neurons. This naming of neurons by their chemical neurotransmitters helps to In a light microscope, light is reflected tell us whether those particular neurons have excitatory or inhibitory effects on other through the specimen and into the eye cells. It also helps to tell us something about the behavior in which the neuron is engaged. of the viewer. In an electron microscope, In the next section, we will look at the structure of a synapse, the site where an electron beam is directed through the chemical communication by means of a neurotransmitter takes place. We will also ex- specimen and onto a reflectant surface, amine the mechanisms that allow the release of a neurotransmitter into a synapse, as where the viewer sees the image. well as the types of synapses that exist in the brain. You will learn how a group of neu- Because electrons scatter less than do rons, all of which use a specific neurotransmitter, can form a system that mediates a light particles, an electron microscope certain aspect of behavior. Damage to such a system results in neurological disorders can show finer details than a light such as Parkinson’s disease (described in “Parkinson’s Disease” on page 156). microscope can show. Whereas a light microscope can be used to see the general features of a cell, an electron The Structure of Synapses microscope can be used to examine the details of a cell’s organelles.