For our purposes, a discussion of neuronal function is largely a discussion of neurotransmission. Neurotransmission is a multistep process that describes the manner in which neurons communicate via the conversion of electrical signals into chemical signals and vice versa. Neurotransmission may result in either:
- Rapid but brief changes in the activation or inhibition of the neuron, via binding of the neurotransmitter with gated ionophore receptors, or
- Longer-term modulatory changes in the actual structure and functioning of the cell, via the binding of the neurotransmitter with a G protein linked receptor. The process by which these long-lasting changes occur is called neuromodulation. Learning about neuromodulation will help you understand memory formation and the basic characteristics of how the brain, as a whole entity, functions and changes over time. This information has implications for treatment of the major psychiatric syndromes and is useful in guiding treatment with both psychotherapy and medication.
The first step in neurotransmission is the production of neurotransmitters. There are primarily three types of neurotransmitters and discussion above): amino acids found in the diet (e.g., glutamate), biogenic amines (serotonin, norepinephrine, and dopamine), and peptides. Amino acids in the bloodstream circulate through the body and into the tissues. In the brain, they are taken up by neurons. Once in the neuron, these amino acids may be used as neurotransmitters or they may be transformed, via various enzymes and steps, into the biogenic amine neurotransmitters (dopamine, norepinephrine, and serotonin). At this point, the neurotransmitters are packaged into the synaptic vesicles and shipped to the axon terminal. They are ready for release when this neuron (neuron A, or presynaptic neuron) is stimulated, causing the electrical signal (which travels along the cell membrane) to arrive at the axon terminal.
Activation and Inhibition of Neurotransmission
The presynaptic cell (neuron A) may be stimulated or inhibited when neurotransmitters bind to the gated ionophore receptors on its cell membrane. This process of activation or inhibition occurs via an opening or closing (respectively) of the ion channels (pores in the membrane). This, in turn, either facilitates or blocks a rush of charged elements (ions) to enter or exit the cell. If the channel is opened, this temporary change in the balance of electrical charges produces an electrical current that is transmitted along the membrane of the axon of neuron A. Within milliseconds of the initial neurotransmitter-receptor binding, the electrical current reaches the axon terminal and the synaptic vesicles, containing the neurotransmitter, empty their contents into the synapse, the space between neuron A (the presynaptic neuron) and neuron B (the postsynaptic neuron). The neurotransmitter released from neuron A almost instantaneously migrates across the synapse to the surface receptors of neuron B. When the neurotransmitter fits into these receptors, the receptor changes shape, causing a cascade of events.
At this point, again depending on the particular receptor-neurotransmitter combination (gated ionophore or G protein linked receptor, and inhibition vs. activation), the neurotransmission process may repeat itself, this time from neuron B to neuron C. Excess neurotransmitter that is not bound to the receptors on the synaptic surface of neuron B is then taken back up into neuron A. This is accomplished by the reuptake pump. Once back inside neuron A, an enzyme called monoamine oxidase (MAO) breaks down the neurotransmitter for recycling or waste.
Alternatively, the ion channel may be blocked, decreasing any chance of neuronal activation and putting an end to the neurotransmission. In this event, no signal is generated to neuron B and the process is over.
The path just described is a rapid response that enables the neuron to react quickly to incoming signals. It does not cause any permanent changes in the neuron. This rapid process occurs when an amino acid neurotransmitter binds to a gate type of receptor. Once the neurotransmitter binds to this receptor, the receptor is able to control the flow of ions into and out of the neuron, through the channels or pores in the membrane. The end result is either inhibition or activation of neurotransmission.
The determining factor of whether a neuron is activated or inhibited is the type of neurotransmitter that binds to the gate receptor. If the neurotransmitter is inhibitory (such as GABA), the neuron is stabilized and its chances of activation are diminished. If the neurotransmitter is glutamate (an excitatory amino acid found in the popular flavor enhancer MSG and involved in neurotoxic effects of alcohol abuse), the neuron is activated.
Another result of neurotransmission is neuromodulation. This process causes more substantive changes (short-term or long-term) in the neuron. Neuromodulation starts with neurotransmission, but only occurs when biogenic amine neurotransmitters bind to the G protein linked receptors. These neurotransmitter-receptor complexes start a cascade of events inside the neuron, cell nucleus, and DNA (as opposed to electrical changes along the membrane in the neurotransmission process). This neuromodulation of neuronal function takes place over minutes, hours, and years, causing changes in the actual structure and function of the nerve cell and the growth of new connections between nerve cells (or conceivably the opposite).
The process of neuromodulation is responsible for short-term and long-term learning, memory, and change. Thus, it is very important for the psychotherapist as well as the biological psychiatrist. For the purpose of understanding these two processes, paths A and B, in greater detail, a useful, although highly imperfect analogy can be made: Think of the neuron as a fast food restaurant. Just as a neuron takes in information and raw materials in order to put out a product (neurotransmitter and information), so does a restaurant. This restaurant has front and rear doors, as well as two types of specialized drive-in windows: windows for ordering, and windows for delivery.
Path A: Routine Neurotransmission
Customers (excitatory neurotransmitters) drive up to the ordering window (bind to gate receptors) to place an order. The food, which is already prepared and wrapped (just as neurotransmitters are prepared and wrapped in synaptic vesicles), is released. A transaction then follows at the delivery window (the pores or ion channels in the membrane) in which substances may be exchanged, and the restaurant is active (the neuron is activated). This is the equivalent of path A. The transaction is transient, efficient, and causes no long-term changes.
Path B: Neuromodulation
Imagine the chain of events, the domino effect that occurs when the restaurant owner finds out from the home office that a new community is being developed in his area, and his business activity will be increasing. He must effectively transmit this message to his restaurant in such a manner that effective, efficient changes will take place, so that he is prepared for the future increase in activity. The restaurant owner (biogenic amine or peptide neurotransmitters) is the first messenger sent from the home office. As the first messenger, he opens the front door lock (the receptor). Putting his key in the lock activates a trigger mechanism (the G protein) that gets the manager’s attention. The owner supplies the letter from the home office containing the following information to the manager (second messenger): “Some new recipes must be activated from our master restaurant management book, and added to the menu. Order more meat, potatoes, and rolls; increase the production of hamburgers. If necessary, buy more equipment to get the job done. Also, construct more drive-in windows, both for ordering and delivery.”
The manager (the second messenger) relays the information to the assistant manager (the third messenger), who in turn orders the chief cook (a transcription factor) to go to the master restaurant management book (DNA), which is locked in a vault (the cell nucleus) for safekeeping. The chief cook copies (copies or transcribes) the requested recipes and necessary construction orders (specific genetic codes) from the book. He then sends them to the assistant cook (messenger RNA), who transforms all the raw materials (hamburger meat, etc.) into the required products (new proteins). The chief cook is a man of many talents, and so he also builds new drive-in windows of both types (receptors and channels).