Aside from direct control of brain activity by specific transmission of nerve signals from the lower brain areas to the cortical regions of the brain, still another physio logical mechanism is often used to control brain activity. This mechanism is to secrete excitatory or inhibitory neu rotransmitter hormonal agents into the substance of the brain. These neurohormones often persist for minutes or hours and thereby provide long periods of control, rather than just instantaneous activation or inhibition.
Figure 1 shows three neurohormonal systems that have been studied in detail in the rat brain: (1) a norepinephrine system, (2) a dopamine system, and (3) a serotonin system. Norepinephrine usually functions as an excitatory hormone, whereas serotonin is usually inhibitory and dopamine is excitatory in some areas but inhibitory in others. As would be expected, these three systems have different effects on levels of excitability in different parts of the brain. The norepinephrine system spreads to virtually every area of the brain, whereas the serotonin and dopamine systems are directed much more to specific brain regions—the dopamine system mainly into the basal ganglial regions and the serotonin system more into the midline structures.
Fig1. Three neurohormonal systems that have been mapped in the rat brain: a norepinephrine system, a dopamine system, and a serotonin system. (Modified from Kandel ER, Schwartz JH [eds]: Principles of Neural Science, 2nd ed. New York: Elsevier, 1985.)
Neurohormonal Systems in the Human Brain. Figure 2 shows the brain stem areas in the human brain for activating four neurohormonal systems, the same three discussed for the rat and one other, the acetylcholine system. Some of the specific functions of these systems are as follows:
1. The locus ceruleus and the norepinephrine system. The locus ceruleus is a small area located bilaterally and posteriorly at the juncture between the pons and mesencephalon. Nerve fibers from this area spread throughout the brain, the same as shown for the rat in the top frame of Figure 1, and they secrete norepinephrine. The norepinephrine generally excites the brain to increased activity. However, it has inhibitory effects in a few brain areas because of inhibitory receptors at certain neuronal synapses. Chapter 60 describes how this system probably plays an important role in causing dreaming, thus leading to a type of sleep called rapid eye movement (REM) sleep.
2. The substantia nigra and the dopamine system. The substantia nigra is discussed in Chapter 57 in relation to the basal ganglia. It lies anteriorly in the superior mesencephalon, and its neurons send nerve endings mainly to the caudate nucleus and putamen of the cerebrum, where they secrete dopa mine. Other neurons located in adjacent regions also secrete dopamine, but they send their endings into more ventral areas of the brain, especially to the hypothalamus and the limbic system. The dopa mine is believed to act as an inhibitory transmitter in the basal ganglia, but in some other areas of the brain it is possibly excitatory. Also, remember from Chapter 57 that destruction of the dopaminergic neurons in the substantia nigra is the basic cause of Parkinson’s disease.
3. The raphe nuclei and the serotonin system. In the midline of the pons and medulla are several thin nuclei called the raphe nuclei. Many of the neurons in these nuclei secrete serotonin. They send fibers into the diencephalon and a few fibers to the cerebral cortex; still other fibers descend to the spinal cord. The serotonin secreted at the cord fiber endings has the ability to suppress pain, which was discussed in Chapter 49. The serotonin released in the diencephalon and cerebrum almost certainly plays an essential inhibitory role to help cause normal sleep, as we discuss in Chapter 60.
4. The gigantocellular neurons of the reticular excitatory area and the acetylcholine system. We previously discussed the gigantocellular neurons (giant cells) in the reticular excitatory area of the pons and mesencephalon. The fibers from these large cells divide immediately into two branches, one passing upward to the higher levels of the brain and the other passing downward through the reticulospinal tracts into the spinal cord. The neurohormone secreted at their terminals is acetylcholine. In most places, the acetylcholine functions as an excitatory neurotransmitter. Activation of these acetylcholine neurons leads to an acutely awake and excited nervous system.
Fig2. Multiple centers in the brain stem, the neurons of which secrete different transmitter substances (specified in parentheses). These neurons send control signals upward into the diencephalon and cerebrum and downward into the spinal cord.
Other Neurotransmitters and Neurohormonal Sub stances Secreted in the Brain. Without describing their function, the following is a partial list of still other neurohormonal substances that function either at specific synapses or by release into the fluids of the brain: enkephalins, gamma-aminobutyric acid, glutamate, vasopressin, adrenocorticotropic hormone, α-melanocyte stimulating hormone (α-MSH), neuropeptide-Y (NPY), epinephrine, histamine, endorphins, angiotensin II, and neurotensin. Thus, there are multiple neurohormonal systems in the brain, the activation of each of which plays its own role in controlling a different quality of brain function.
