aAdapted from [44].
Fig. 2.14 Anatomic components of the central autonomic network. The diagram of the human brain indicates the areas involved in central autonomic control, as defined by animal studies. The insular cortex is the primary viscerosensory area. The central nucleus of the amygdala is involved in emotional responses. The paraventricular, lateral and other hypothalamic regions are involved in homeostasis and adaptive behavior. The periaqueductal gray integrates autonomic, motor, and antinociceptive receptive responses during stress. The parabrachial region is a viscerosensory relay and participates in cardiovascular and respiratory control. The nucleus of the tractus solitarii (nucleus of the solitary tract) is the primary viscerosensory relay nucleus. The ventrolateral medulla contains sympathoexcitatory, sympathoinhibitory, and respiratory neurons. The nucleus ambiguus contributes innervation to the heart. The intermediate reticular zone of the medulla (shaded area) is critically involved in integration of respiratory, cardiovascular, and other autonomic reflexes. (From [45], with permission)
The autonomic nervous system often works as a servo system enabling responsiveness to a variety of local and systemic influences, with interaction and at times control at different levels of the neural axis. Thus, every afferent in the body can influence parasympathetic and sympathetic efferent activity (Fig. 2.16). Examples are visual afferents (through cranial nerve II) that influence pupillary function; chemoreceptors, sinoaortic baroreceptors, and low-pressure receptors through cranial nerves IX and X, which regulate cardiac vagal and sympathetic neural control of heart and blood vessels; and visceral, skin, and muscle receptors (through cerebral connections or via the isolated spinal cord as observed in patients with high spinal cord lesions), which influence a wide range of autonomic activity.
Fig. 2.15 Outline of the major transmitters at autonomic ganglia and postganglionic sites on target organs supplied by the sympathetic and parasympathetic efferent pathways. The acetylcholine receptor at all ganglia is of the nicotinic subtype (ACh-n). Ganglionic blockers such as hexamethonium thus prevent both parasympathetic and sympathetic activation. Atropine, however, acts only on the muscarinic (ACh-m) receptor at postganglionic parasympathetic and sympathetic cholinergic sites. The cotransmitters along with the primary transmitters are also indicated. NA, norepinephrine (noradrenaline); VIP, vasoactive intestinal polypeptide; NPY, neuropeptide Y. (From [44], with permission)
Fig. 2.16 Schema to indicate the major afferent pathways that influence the major autonomic efferent outflow (the cranial and sacral parasympathetic and the thoracolumbar sympathetic), supplying various organs. Cr = Cranial nerve (From [44], with permission)
Fig. 2.17 Schema of pathways in the formation, release, and metabolism of norepinephrine from sympathetic nerve terminals. Tyrosine is converted into dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase (TH). DOPA is converted Into dopamine (DA) by dopadecarboxylase. In the vesicles DA is converted into norepinephrine (noradrenaline, NA) by dopamine β-hydroxylase (DβH). Nerve impulses release both DβH and NA into the synaptic cleft by exocytosis. NA acts predominantly on α1-adrenoceptors but has actions on β-adrenoceptors on the effector cell of target organs. It also has presynaptic adrenoceptor effects. Those acting on α2-adrenoceptors inhibit NA release: those on β-adrenoceptors stimulate NA release. NA may be taken up by a neuronal process (uptake 1) into the cytosol, where it may inhibit further formation of DOPA through the rate-limiting enzyme TH. NA may be taken into vesicles or metabolized by monoamine oxidase (MAO) in the mitochondria. NA may be taken up by a higher-capacity but lower-affinity extraneuronal process (uptake 2) into peripheral tissues, such as vascular and cardiac muscle and certain glands. NA is also metabolized by catechol-o-methyl transferase (COMT). NA measured in plasma is the overspill not affected by these numerous processes. (From [44], with permission)
There is increasing evidence in humans, resulting from a combination of neuroendocrine and neuroimaging studies, of the role of various cerebral areas that control, influence, and modulate autonomic function. This is in keeping with extensive experimental data of the role of the insular cortex and amygdala in cardiovascular responses, and of hypothalamic nucleii in neuroendocrine control.
In the enteric nervous system, prevertebral ganglia (celiac, superior and inferior mesenteric) have both sympathetic and parasympathetic efferents and a system of neurons and supporting cells within various viscera including the gastrointestinal tract, pancreas, and gall bladder. These innervate the musculature of the alimentary tract (and thus influence gut motility), the secretion of organs (such as the flow of gastric acid), mucosal blood flow, and the intestinal transport of water and electrolytes. There are sensory neurons that monitor factors such as tension in the walls of the intestine or the chemical nature of its content, and associated neurons (interneurons) that link information between enteric and motor neurons and influence smooth muscle contraction, vasodilatation, and transport of water and electrolytes. They interact with sympathetic and parasympathetic pathways and the wide range of enteric endocrine cells, with numerous pancreatic and gut peptides that have roles both locally and elsewhere. Within the enteric nervous system are a number of interconnected networks or plexuses. In the intestines these include the myenteric (Auerbach's) plexus between the external longitudinal and circular muscle coats, and the subserous (Meissner's) plexus in the connective tissue between the serosal mesothelium and external muscle. The major neurotransmitter is acetylcholine, and these plexuses are thus similar to the intrinsic plexuses found in the heart that also are the sites of selective involvement in Chagas' disease following infection with Trypanosoma cruzi; dysfunction may result from a specifically targeted immunological process.
Fig. 2.18 Schema of pathways in the formation from choline of acetylcholine (ACh) and its inactivation by acetylcholine esterase (AChE). (From [46], with permission)
The postganglionic autonomic supply to organs and effector cells consists of multiple neurotransmitters with complex machinery relating to their formation, release, interplay with other substances, uptake, and recycling. Schema for the threemajor neurotransmitters, norepinephrine in adrenergic, acetylcholine in cholinergic, and adenosine triphosphate in purinergic terminals, are provided in Figures 2.17-2.19. A variety of other substances may be cosecreted, examples being vasoactive intestinal polypeptide with acetylcholine, and neuropeptide Y with norepinephrine (Fig. 2.15). This may explain the inability of specific antagonists to block all the effects of parasympathetic and sympathetic nerve stimulation, as observed with the muscarinic blocker atropine and with α-adrenoceptor blockers, respectively.