Neurotransmitters are chemicals that transmit signals from a neuron to a target cell across a synapse. When called upon to deliver messages, they are released from their synaptic vesicles on the presynaptic (giving) side of the synapse, diffuse across the synaptic cleft, and bind to receptors in the membrane on the postsynaptic (receiving) side.
An action potential is necessary for neurotransmitters to be released, which means that neurons must reach a certain threshold of electric stimulation in order to complete the reaction. A neuron has a negative charge inside the cell membrane relative to the outside of the cell membrane; when stimulation occurs and the neuron reaches the threshold of excitement this polarity is reversed. This allows the signal to pass through the neuron. When the chemical message reaches the axon terminal, channels in the postsynaptic cell membrane open up to receive neurotransmitters from vesicles in the presynaptic cell.
Inhibitory neurotransmitters cause hyperpolarization of the postsynaptic cell (that is, decreasing the voltage gradient of the cell, thus bringing it further away from an action potential), while excitatory neurotransmitters cause depolarization (bringing it closer to an action potential). Neurotransmitters match up with receptors like a key in a lock. A neurotransmitter binds to its receptor and will not bind to receptors for other neurotransmitters, making the binding a specific chemical event.
There are several systems of neurotransmitters found at various synapses in the nervous system. The following groups refer to the specific chemicals, and within the groups are specific systems, some of which block other chemicals from entering the cell and some of which permit the entrance of chemicals that were blocked before.
Cholinergic System
The cholinergic system is a neurotransmitter system of its own, and is based on the neurotransmitter acetylcholine (ACh). This system is found in the autonomic nervous system, as well as distributed throughout the brain.
The cholinergic system has two types of receptors: the nicotinic receptor and the acetylcholine receptor, which is known as the muscarinic receptor. Both of these receptors are named for chemicals that interact with the receptor in addition to the neurotransmitter acetylcholine. Nicotine, the chemical in tobacco, binds to the nicotinic receptor and activates it similarly to acetylcholine. Muscarine, a chemical product of certain mushrooms, binds to the muscarinic receptor. However, they cannot bind to each others' receptors.
Amino Acids
Another group of neurotransmitters are amino acids, including glutamate (Glu), GABA (gamma-aminobutyric acid, a derivative of glutamate), and glycine (Gly). These amino acids have an amino group and a carboxyl group in their chemical structures. Glutamate is one of the 20 amino acids used to make proteins. Each amino acid neurotransmitter is its own system, namely the glutamatergic, GABAergic, and glycinergic systems. They each have their own receptors and do not interact with each other. Amino acid neurotransmitters are eliminated from the synapse by reuptake. A pump in the cell membrane of the presynaptic element, or sometimes a neighboring glial cell, clears the amino acid from the synaptic cleft so that it can be recycled, repackaged in vesicles, and released again.
The reuptake process
This illustration shows the process of reuptake, in which leftover neurotransmitters are returned to vesicles in the presynaptic cell.
Biogenic Amines
Another class of neurotransmitter is the biogenic amine, a group of neurotransmitters made enzymatically from amino acids. They have amino groups in them, but do not have carboxyl groups and are therefore no longer classified as amino acids.
Neuropeptides
A neuropeptide is a neurotransmitter molecule made up of chains of amino acids connected by peptide bonds, similar to proteins. However, proteins are long molecules while some neuropeptides are quite short. Neuropeptides are often released at synapses in combination with another neurotransmitter.
Dopamine
Dopamine is the best-known neurotransmitter of the catecholamine group. The brain includes several distinct dopamine systems, one of which plays a major role in reward-motivated behavior. Most types of reward increase the level of dopamine in the brain, and a variety of addictive drugs increase dopamine neuronal activity. Other brain dopamine systems are involved in motor control and in controlling the release of several other important hormones.
Effect on the Synapse
The effect of a neurotransmitter on the postsynaptic element is entirely dependent on the receptor protein. If there is no receptor protein in the membrane of the postsynaptic element, then the neurotransmitter has no effect. The depolarizing (more likely to reach an action potential) or hyperpolarizing (less likely to reach an action potential) effect is also dependent on the receptor. When acetylcholine binds to the nicotinic receptor, the postsynaptic cell is depolarized. However, when acetylcholine binds to the muscarinic receptor, it might cause depolarization or hyperpolarization of the target cell.
The amino acid neurotransmitters (glutamate, glycine, and GABA) are almost exclusively associated with just one effect. Glutamate is considered an excitatory amino acid because Glu receptors in the adult cause depolarization of the postsynaptic cell. Glycine and GABA are considered inhibitory amino acids, again because their receptors cause hyperpolarization, making the receiving cell less likely to reach an action potential.
The Right Dose
Sometimes too little or too much of a neurotransmitter may affect an organism's behavior or health. The underlying cause of some neurodegenerative diseases, such as Parkinson's, appears to be related to overaccumulation of proteins, which under normal circumstances would be regulated by the presence of dopamine. On the other hand, when an excess of the neurotransmitter dopamine blocks glutamate receptors, disorders like schizophrenia can occur.