5-1 A Chemical Message

In the 1920s, Otto Loewi suspected that nerves to the heart secrete a chemical that regulates its beat rate. His subsequent experiments with frogs showed that acetylcholine slows heart rate, whereas epinephrine increases it. This observation proved key to understanding the basis of chemical neurotransmission.

The systems for chemically synthesizing an excitatory or inhibitory neurotransmitter are in the presynaptic neuron’s axon terminal or its soma, whereas the systems for neurotransmitter storage are in its axon terminal. The receptor systems on which that neurotransmitter acts typically are on the postsynaptic membrane. Such chemical neurotransmission is dominant in the human nervous system. Nevertheless, neurons also make direct connections with each other through gap junctions, channel-forming proteins that allow direct sharing of ions or nutrients.

The four major stages in the life of a neurotransmitter are (1) synthesis and storage, (2) release from the axon terminal, (3) action on postsynaptic receptors, and (4) inactivation. After synthesis, the neurotransmitter is wrapped in a membrane to form synaptic vesicles in the axon terminal. When an action potential is propagated on the presynaptic membrane, voltage changes set in motion the vesicles’ attachment to the presynaptic membrane and neurotransmitter release by exocytosis.

One synaptic vesicle releases a quantum of neurotransmitter into the synaptic cleft, producing a miniature potential on the postsynaptic membrane. To generate an action potential on the postsynaptic cell requires simultaneous release of many quanta of transmitter. After a transmitter has done its work, it is inactivated by such processes as diffusion out of the synaptic cleft, breakdown by enzymes, and reuptake of the transmitter or its components into the axon terminal (or sometimes uptake into glial cells).

5-2 Varieties of Neurotransmitters and Receptors

Small-molecule transmitters, peptide transmitters, lipid transmitters, and gaseous transmitters are broad classes for ordering the roughly 100 neurotransmitters that investigators propose might exist. Neurons containing these transmitters make a variety of connections with other neurons as well as with muscles, blood vessels, and extracellular fluid.

Functionally, neurons can be both excitatory and inhibitory, and they can participate in local circuits or in general brain networks. Excitatory synapses are usually on a dendritic tree, whereas inhibitory synapses are usually on a cell body.

Some neurotransmitters are associated with both ionotropic and metabotropic receptors. An ionotropic receptor quickly and directly induces voltage changes on the postsynaptic cell membrane. Slower-acting metabotropic receptors activate second messengers to indirectly produce changes in the cell’s function and structure. A plethora of receptors, formed from combinations of multiple types of proteins called subunits, exist for most transmitters.

5-3 Neurotransmitter Systems and Behavior

Because neurotransmitters are multifunctional, scientists find it impossible to isolate relations between a single neurotransmitter and a single behavior. Rather, activating systems of neurons that employ the same principal neurotransmitter influence various general aspects of behavior. For instance, acetylcholine, the main neurotransmitter in the SNS, controls movement of the skeletal muscles, whereas acetylcholine and norepinephrine, the main neurotransmitters in the ANS, control the body’s internal organs. In the ENS, dopamine and serotonin serve as the main neurotransmitters regulating the gut’s functioning.

The CNS contains not only widely dispersed glutamate and GABA neurons—its main neurotransmitters—but also neural activating systems that employ acetylcholine, norepinephrine, dopamine, or serotonin. All these systems ensure that wide areas of the brain act in concert, and each is associated with various classes of behaviors and disorders.

5-4 Adaptive Role of Synapses in Learning and Memory

Changes in synapses underlie the neural basis of learning and memory. In habituation, a form of learning in which a response weakens as a result of repeated stimulation, calcium channels become less responsive to an action potential. Consequently, less neurotransmitter is released when an action potential is propagated.

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In sensitization, a form of learning in which a response strengthens as a result of stimulation, changes in potassium channels prolong the action potential’s duration, resulting in an increased influx of calcium ions and consequently, release of more neurotransmitter. With repeated training, new synapses can develop, and both forms of learning can become relatively permanent.

In Aplysia, the number of synapses connecting sensory neurons and motor neurons decreases in response to repeated sessions of habituation. Conversely, the number of synapses connecting sensory and motor neurons increases in response to repeated sensitization sessions. These changes in the numbers of synapses and dendritic spines are related to long-term learning.