Neurotransmitters—an Introduction :
As we discuss in Part 1 of CorticalBrain.com, in Neurons, neurochemicals, and neurocircuits, each neuron has a very slender axon—a kind of nerve fiber—that projects from the neuron's cell body and transmits electrical impulses to the neuron's axon terminals. This electrical signal stimulates release of a neurotransmitter, which is produced inside the nerve cell. It is neurotransmitters that light up the brain with life.
Neurotransmitters operate in distinct systems made up of neurons communicating together in circuits. As we discuss in Part 1 of CorticalBrain.com, a bundle of axons from neuron cell bodies appears as white matter and either projects to a given target structure (projection) or links together several target structures (pathway). We will discuss only the most prominent neurotransmitter pathways in the following narrative. For example, there are eight neural pathways in the brain that function via dopamine transmission, but we will discuss only four.
Monoamines and catecholamines—notes on molecular structure:
Monoamines: The major neurotransmitters we will discuss here (serotonin, dopamine, norepinephrine, and epinephrine) are all monoamines. Monoamines contain one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). The molecular structure for the neurotransmitter serotonin is pictured at left. Serotonin is derived from the amino acid L-tryptophan.
Catecholamines: Three of the monoamines described above (dopamine, norepinephrine, and epinephrine) are also called catecholamines because they contain a catechol group. Catecholamines are a group of neurotransmitters that arise in sequence from the amino acid tyrosine. Tyrosine is created from phenylalanine via hydroxylation by the enzyme phenylalanine hydroxylase. (Tyrosine is also ingested directly from dietary protein). It is then sent to catecholamine-secreting neurons where many kinds of reactions convert it to dopamine, to norepinephrine, and eventually to epinephrine.
Serotonin action, synthesis, and pathways:
Action: In Evolving Brains (2000), John Allman explains that serotonin often "does not directly excite other neurons but instead modulates the responses of neurons to other neurotransmitters." What this means is that neurotransmitters such as norepinephrine and dopamine do not act in a vacuum. The transmission of serotonin has a strong influence on the transmission of these and other neurotransmitters. One exception where serotonin directly excites neurons is in the cerebral cortex, where it excites pyramidal neurons. A pyramidal neuron's cell body, or soma, is shaped like a triangle, thus the name pyramidal neuron. In addition to a single axon and multiple basal dendrites, pyramidal neurons have a large apical dendrite arising from the apex of the soma that branches several times. Examples of pyramidal cells, the kind of cell serotonin targets in the cerebral cortex, are shown below (image links to source). These images are from the Veterinary Neurohistology Atlas produced by T.F. Fletcher and supported by the University of Minnesota College of Veterinary Medicine
Allman illuminates the importance of serotonin in the brain. He writes:
The axons of the serotonergic neurons project in rich profusion to every part of the central nervous system (the brain and spinal cord), where they influence the activity of virtually every neuron. This widespread influence implies that the serotonergic neurons play a fundamental role in the integration of behavior. Our sense of well-being and our capacity to organize our lives and to relate to others depend profoundly on the functional integrity of the serotonergic system. There are only a few hundred thousand serotonergic neurons in the human brain, roughly one millionth of the total population of neurons in the human central nervous system. However, the serotonin receptors on the target neurons are remarkably diverse. Fourteen types of serotonin receptors have been discovered so far in the brains of mammals, located in different places and acting in different ways.
Synthesis: Most serotonin in the human body is found in the enterochromaffin cells in the gastrointestinal tract, where it is used to regulate intestinal movements. In the brain, the neurons of the raphe nuclei are the principal source of serotonin release. The term "raphe" is Greek for a ridge or seam between two parts, particularly symmetrical parts. As are most other structures in the brain, the raphe nuclei are grouped into pairs and distributed along one of the phylogenetically oldest portions of the brain, the reticular formation. As we discuss in Part 1 of CorticalBrain.com, in Brain stem structures and the reticular formation, the reticular formation is the core of the brain stem, running from the lower medulla oblongata through the pons and into the mid-brain. A quotation from John Allman's Evolving Brains bears repeating here: "The cell bodies of the serotonergic neurons occupy virtually the same location in the basement of every vertebrate brain and are even in the same spot in the central nervous system of amphioxus, a primitive chordate." (As mentioned earlier, chordates have notocords, a simple central nervous system. Chordates include fish and very primitive sea creatures.)
Allman explains that serotonin "is made from the amino acid tryptophan, which is abundant in meat and fowl. (The human body cannot make tryptophan, and thus we must obtain it from dietary sources. Tryptophan deprivation alters brain chemistry and mood.) Tryptophan is obtained by the digestion of proteins in the gut and is transported in the blood plasma to the brain, where it is converted to serotonin."
Pathways: Axons of neurons in the lower raphe nuclei terminate in the spinal cord as well as the cerebellum's deep nuclei and cortex. Axons of neurons in the higher raphe nuclei terminate in 1) subcortical nuclei including the centrally located thalami; the surrounding corpus striata including the nucleus accumbens; the hypothalamus, hippocampus, and amygdala, 2) the cingulate cortex, including the cingulum, a tract of association fibers connecting the corpus callosum with the hippocampus, and 3) the neocortex. If you have pictured this innervation in your mind, you now understand that serotonin innervates the entire brain, bottom to top.
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