Once a neural signal reaches the axon terminals of a neuron, several events take place to allow neurons to communicate with each other. These events are dependent upon key structures within a neuron and on the surface of adjacent neurons.

Figure 2.3 shows an axon terminal enlarged to giant scale. Notice that the presynaptic terminal is not empty. It has a number of little sac-like structures in it called synaptic vesicles. The word vesicle is Latin and means a “little blister” or “fluid-filled sac.”

Figure 2.3

The Synapse

Inside the synaptic vesicles are chemicals suspended in fluid, which are molecules of substances called neurotransmitters. The name is simple enough—they are inside a neuron and they are going to transmit a message. (Neurons have traditionally been viewed as containing a single type of neurotransmitter, but it is now accepted that neurons may release more than one neurotransmitter. For simplicity and unless otherwise specified, our discussion throughout the text will assume a single, predominant neurotransmitter is being released.) Next to the synaptic knob is the dendrite of another neuron (see Figure 2.3). Between them is a fluid-filled space called the synapse (synaptic gap). Instead of an electrical charge, the vesicles at the end of the axon (also called the presynaptic membrane) contain the molecules of neurotransmitters, and the surface of the dendrite next to the axon (the postsynaptic membrane) contains ion channels that have receptor sites, proteins that allow only particular molecules of a certain shape to fit into it, just as only a particular key will fit into a keyhole.

How do the neurotransmitters get across the gap? Recall the action potential making its way down the axon after the neuron has been stimulated. When that action potential, or electrical charge, reaches the synaptic vesicles, the synaptic vesicles release their neurotransmitters into the synaptic gap. The molecules then float across the synapse and many of them fit themselves into the receptor sites, opening the ion channels and allowing sodium to rush in, activating the next cell. It is this very activation that stimulates, or releases, the action potential in that cell. It is important to understand that the “next cell” may be a neuron, but it may also be a cell on a muscle or a gland. Muscles and glands have special cells with receptor sites on them, just like on the dendrite of a neuron.

So far, we’ve been talking about the synapse as if neurotransmitters always cause the next cell to fire its action potential (or, in the case of a muscle or gland, to contract or start secreting its chemicals). But the neurons must have a way to be turned off as well as on. Otherwise, when a person burns a finger, the pain signals from those neurons would not stop until the burn was completely healed. Muscles are told to contract or relax, and glands are told to secrete or stop secreting their chemicals. The neurotransmitters found at various synapses around the nervous system can either turn cells on (called an excitatory effect) or turn cells off (called an inhibitory effect), depending on exactly what synapse is being affected. Although some people refer to neurotransmitters that turn cells on as excitatory neurotransmitters and the ones that turn cells off as inhibitory neurotransmitters, it’s really more correct to refer to excitatory synapses and inhibitory synapses. In other words, it’s not the neurotransmitter itself that is excitatory or inhibitory, but rather it is the effect of that neurotransmitter that is either excitatory or inhibitory at the receptor sites of a particular synapse.

The first neurotransmitter to be identified was named acetylcholine (ACh). It is found at the synapses between neurons and muscle cells. Acetylcholine serves to stimulate the skeletal muscles to contract but actually slows contractions in the heart muscle. If acetylcholine receptor sites on the muscle cells are blocked in some way, then the acetylcholine can’t get to the site and the muscle will be incapable of contracting—paralyzed, in other words. This is exactly what happens when curare, a drug used by South American Indians on their blow darts, gets into the nervous system. Curare’s molecules are just similar enough to fit into the receptor site without actually stimulating the cell, making curare an antagonist (a chemical substance that blocks or reduces the effects of a neurotransmitter) for ACh.

What would happen if the neurons released too much ACh? The bite of a black widow spider does just that. Its venom stimulates the release of excessive amounts of ACh and causes convulsions and possible death. Black widow spider venom is an agonist (a chemical substance that mimics or enhances the effects of a neurotransmitter) for ACh.

ACh also plays a key role in memory, arousal, and attention. For example, ACh is found in the hippocampus, an area of the brain that is responsible for forming new memories, and low levels of ACh have been associated with Alzheimer’s disease, the most common type of dementia. (See Learning Objective 6.14.) We will focus more on agonists and antagonists later in the chapter.

Since the discovery of ACh, many other neurotransmitters have been identified. These substances have a variety of roles ranging from general excitatory and inhibitory effects to influencing eating, sleeping, movement, and consciousness. Others influence cognition, memory, and mood. Refer to Table 2.1 for an overview of various neurotransmitters and their functions.

A group of substances known as neuropeptides can serve as neurotransmitters, hormones, or influence the action of other neurotransmitters (Schwartz & Javitch, 2013). You may have heard of the set of neuropeptides called endorphins—pain-controlling chemicals in the body. When a person is hurt, a neurotransmitter that signals pain is released. When the brain gets this message, it triggers the release of endorphins. The endorphins bind to receptors that open the ion channels on the axon. This causes the cell to be unable to fire its pain signal and the pain sensations eventually lessen. For example, you might bump your elbow and experience a lot of pain at first, but the pain will quickly subside to a much lower level. Athletes may injure themselves during an event and yet not feel the pain until after the competition is over, when the endorphin levels go down.

The name endorphin comes from the term endogenous morphine. (Endogenous means “native to the area”—in this case, native to the body.) Scientists studying the nervous system found receptor sites that fit morphine molecules perfectly and decided that there must be a natural substance in the body that has the same effect as morphine. Endorphins are the reason that heroin and the other drugs derived from opium are so addictive—when people take morphine or heroin, their bodies neglect to produce endorphins. When the drug wears off, they are left with no protection against pain at all, and everything hurts. This pain is why most people want more heroin, creating an addictive cycle of abuse. (See Learning Objective 4.11.)

 If the neurotransmitters are out there in the synaptic gap and in the receptor sites, what happens to them when they aren’t needed anymore?

 The neurotransmitters have to get out of the receptor sites before the next stimulation can occur. Some just drift away through the process of diffusion, but most will end up back in the synaptic vesicles in a process called reuptake. (Think of a little suction tube, sucking the chemicals back into the presynaptic neuron, to be repackaged into the vesicles.) In this way the synapse is cleared for the next release of neurotransmitters. Some drugs, like cocaine, affect the nervous system by blocking the reuptake process, as shown in Video Figure 2.4: Neurotransmitters: Reuptake.

There is one neurotransmitter that is not taken back into the vesicles, however. Because ACh is responsible for muscle activity, and muscle activity needs to happen rapidly and continue happening, it’s not possible to wait around for the “sucking up” process to occur. Instead, an enzymemore info specifically designed to break apart ACh clears the synaptic gap very quickly (a process called enzymatic degradation). There are enzymes that break down other neurotransmitters as well.

 I think I understand the synapse and neurotransmitters now, but how do I relate that to the real world?

Knowing how and why drugs affect us can help us understand why a physician might prescribe a particular drug or why certain drugs are dangerous and should be avoided. Because the chemical molecules of various drugs, if similar enough in shape to the neurotransmitters, can fit into the receptor sites on the receiving neurons just like the neurotransmitters do, drugs can act as agonists or antagonists. Drugs acting as agonists, for example, can mimic or enhance the effects of neurotransmitters on the receptor sites of the next cell. This can result in an increase or decrease in the activity of the receiving cell, depending on what the effect of the original neurotransmitter (excitatory or inhibitory) was going to be. So if the original neurotransmitter was excitatory, the effect of the agonist will be to increase that excitation. If it was inhibitory, the effect of the agonist will be to increase that inhibition. Another deciding factor is the nervous system location of the neurons that use a specific neurotransmitter.

For example, some antianxiety medications, such as diazepam (Valium^®), are classified as benzodiazepines (See Learning Objective 13.10.) and are agonists for GABA, the primary inhibitory neurotransmitter in the brain. Areas of the brain that you will learn about later that play a role in controlling anxiety, agitation, and fear include the amygdala, orbitofrontal cortex, and the insula (LeDoux & Damasio, 2013; Zilles & Amunts, 2012). By increasing the inhibitory (calming) action of GABA, the benzodiazepines directly calm these specific brain areas (Julien et al., 2011; Preston et al., 2008).

Other drugs act as antagonists, blocking or reducing a cell’s response to the action of other chemicals or neurotransmitters. Although an antagonist might sound like it has only an inhibitory effect, it is important to remember that if the neurotransmitter that the antagonist affects is inhibitory itself, the result will actually be an increase in the activity of the cell that would normally have been inhibited; the antagonist blocks the inhibitory effect.

Lastly, some drugs yield their agonistic or antagonistic effects by impacting the amount of neurotransmitter in the synapse. They do so by interfering with the regular reuptake or enzymatic degradation process. Remember that the neurotransmitter serotonin helps regulate and adjust people’s moods, but in some people the normal process of adjustment is not working properly. Some of the drugs used to treat depression are called SSRIs (selective serotonin reuptake inhibitors). SSRIs block the reuptake of serotonin, leaving more serotonin available in the synapse to bind with receptor sites. Over several weeks, the individual’s mood improves. Although the reason for this improvement is not as simple as once believed (i.e., low levels of serotonin = low levels of mood) or fully understood, SSRIs are effective for depression, anxiety, and obsessive-compulsive disorder (Hyman & Cohen, 2013; Julien et al., 2011; Stahl, 2013).

This section covered the neuron and how neurons communicate. The next section looks at the bigger picture—the nervous system itself.