The Enlarged Autonomic Nervous System

Abstract

The traditional view of the autonomic nervous system (ANS) considers only its peripheral part, the sympathetic and parasympathetic systems, to which sometimes the enteric ANS is added as an independent entity. However, this view is insufficient to understand the most important function of the ANS: the maintenance of homeostasis. This Chapter describes the hierarchical organization of the autonomic motor pathways and their similarities with the somatic motor organization. It analyzes the types of neurons, neuronal circuits, and electric potentials identified in autonomic neurons.

FormalPara Objectives

After studying this chapter, you should be able to:

• Describe the control of reactive and predictive homeostasis as the most important function of the ANS

• Describe the hierarchical organization of the autonomic and somatic motor pathways and their similarities

• Name the components of the autonomic posture in comparison with the mechanisms of body posture

• Describe the two types of neurons and the three neuronal circuits that give rise to the basic neuronal organization of ANS

• Name the different types of electrical potentials identified in autonomic neurons

The Control of Homeostasis Is the Most Important Function of the ANS

The traditional view of the autonomic nervous system (ANS) considers only its peripheral part, the sympathetic and parasympathetic systems, to which sometimes the enteric ANS is added as an independent entity. However, this view is insufficient to understand the most important function of the ANS: the maintenance of homeostasis.

The term “homeostasis” was coined by the distinguished American physiologist Walter B. Cannon as a comprehensive concept to describe the physiological factors that maintain the equilibrium state of the body, and therefore, life [1]. Following Claude Bernard, Cannon perfected the idea of the constancy of the internal environment, giving it its present meaning. As explained by Cannon, he chose as a prefix homeo- (“like”) instead of homo- (“the same”) to take into account the normal variations that any physiological variable exhibits, thus avoiding the misleading consideration of a “constant (fixed) internal milieu.”

The development of chronobiology as an independent discipline added another aspect to homeostasis. This term is used today to define not only the strategies that allow the organism’s proper response to changes in the environment (“reactive homeostasis”), but also the time-related mechanisms, remarkably developed, that allow the body to predict the occurrence of a given environmental stimulus to initiate the appropriate corrective responses beforehand (“predictive homeostasis”) [2]. Predictive homeostasis comprises the anticipatory mechanisms that precede a regularly occurring environmental phenomenon, thus facilitating a better physiological adaptation to it. For example, the increase in plasma cortisol that precedes waking anticipates the energy demands of a changing posture; the increased gastrointestinal secretion preceding the usual lunch time anticipates the changes in the content of the digestive tract.

Let us suppose that a diurnally active mammal in search of food finds the food at a place about 2 h from the shelter it uses to escape its predator at night. This situation makes it essential for the animal to predict nightfall about 2 h in advance. It do this using the position of the sun or other environmental variables, such as temperature or humidity. However, the existence of clouds or a large daily variation in ambient temperature make the value of such reference parameters unreliable. It is then extremely useful for survival to possess a system of time control integrated into its own organism that allows a temporal prediction without having to depend on the reading of external signals. This was probably the strategy selected as an advantage by evolution.

The circadian clock is ideal to fulfill such a function: we could have a sufficiently accurate idea of the time of day by simply analyzing our biological structure periodically and without consulting our wristwatch. That is, a “day” and “night” have been created within the organism to allow it to optimize adaptation [3].

Generally, the nervous system can produce a small number of actions: (a) the contraction of a muscle or of a group of striated or smooth muscles; (b) the exocrine, endocrine, or paracrine secretion of a cell or cell group; (c) changes in cellular permeability. This is achieved via motor neurons , which can be classified per their targets into three categories:

• Somatic motor neurons , which originate in the central nervous system (CNS), project their axons to the skeletal muscles (such as the muscles of the limbs, abdominal, and intercostal muscles) that are involved in locomotion.

• Special visceral motor neurons , also called branchial motor neurons , which directly innervate the branchial muscles (that motorize the gills in fish and the face and neck in land vertebrates).

• Visceral preganglionic neurons , which indirectly innervate the heart, the smooth muscle in all organs, the abdominal viscera, the exocrine and endocrine glands, and the immune system. They synapse onto neurons located in the autonomic ganglia of the ANS (sympathetic and parasympathetic postganglionic neurons).

As a consequence: (a) the motor command of skeletal and branchial muscles is monosynaptic (involving only one motor neuron, somatic and branchial respectively, which synapses onto the muscle); (b) the command of the viscera is disynaptic, involving two neurons, the visceral preganglionic neuron located in the CNS, which synapses onto a postganglionic neuron, which synapses onto the organ.

The ANS, which is in charge of the innervation of smooth muscles of all organs and innervation of the viscera, immune tissue, and exocrine and endocrine glands, can produce the three actions mentioned above (smooth muscle contraction; exocrine, endocrine, or paracrine secretion; permeability changes). It must be noted that for the command of visceral muscles, the ganglionic neuron, parasympathetic or sympathetic, is the real motor neuron, as it is the one that directly innervates the muscle, whereas the general visceral motor neuron is, strictly speaking, the preganglionic one [4].

All vertebrate motor neurons are cholinergic, that is, they release the neurotransmitter acetylcholine (ACh). Parasympathetic ganglionic neurons are also cholinergic, whereas most sympathetic ganglionic neurons are noradrenergic, that is, they release the neurotransmitter norepinephrine (NE) .

It is not unusual to hear or read or to remain implicit that actions of the sympathetic and parasympathetic divisions promote opposite effects in the organs they innervate. However, for the precise aim of a homeostatic response requiring effectiveness, energy economy, and sometimes a fast response, the sympathetic and parasympathetic neurons must collaborate for the final net effect.

In general, the sympathetic activity is designed to place the individual in a situation of defense in the face of danger, real or potential. Sympathetic stimulation leads to variations in visceral functions designed to protect the integrity of the organism and to ensure survival. In fact, a sympathectomized animal hardly survives if left free and exposed in its natural environment. However, in addition to calm and resting states, our daily life involves many perturbations that induce active conditions such as locomotion, eating, and communication. Thus, the mobilization of physiological variables does not occur in an all-or-nothing manner and is not exclusive of extreme “fight or flight” conditions; rather, they can occur with graded intensities in ordinary daily situations. During such active periods, cardiovascular, respiratory, and body temperature regulation needs to be adjusted to situational demands, which differ from those during resting states, by modulating or resetting homeostatic points. For instance, if an increase in blood pressure (BP) is needed, a greater gain in the response can be obtained by the concomitant enhancement of sympathetic activity and inhibition of parasympathetic activity. This is obtained not only in the CNS areas, but also via reciprocal inhibitory connections at the level of the heart wall [5].

Autonomic nervous system activity adapts to body changes and supports somatic reactions. The autonomic response may be secondary to the somatic, parallel to, or, most commonly, before (the “autonomic posture”) [3]. The ANS is designed to produce sustained actions, compared with those of the somatic nervous system. On the other hand, the ANS performs this multisystem control in a continuous and constant manner throughout the life cycles, both at rest and during activity in the three body configurations within a 24 h cycle discussed in Chap. 2.

One of the most surprising features of the ANS is the speed and intensity with which it modifies the visceral functions. In a few seconds, for example, the heart rate and BP can increase up to double the normal rates, there may be intense sweating, the urinary bladder may empty, or digestive motility and secretion may be activated.

The sympathetic stimulation causes general responses in the organism for two reasons. First, there is a high degree of irradiation of the connections between preganglionic and postganglionic neurons. The proportion of preganglionic fibers to postganglionic neurons in sympathetic ganglia is 1/4–1/30, and since the degree of axonal branching is high, it is estimated that each preganglionic axon contacts an average of 120 neurons. For this reason, the activity of a few preganglionic neurons is highly amplified numerically via their ganglionic connections. Second, sympathetic activity produces a stimulation of the secretion of catecholamines from the adrenal medulla. In circulation, almost all epinephrine (E) found is derived from the adrenal medulla, but only 20% of the NE is. The rest of the circulating NE comes from the peripheral sympathetic terminals, i.e., as the neurotransmitter that has escaped presynaptic reuptake.

A massive activation of the sympathetic system produces a set of reactions defined as an alarm response (fight or flight) [6]. The most obvious visceral phenomena of this massive activation are:

• Pupil dilation, to increase the visual field

• Piloerection, to simulate a larger body size

• Sweating, to lose heat that is produced by muscular activity

• Increased cardiac activity and BP, to provide greater blood flow to the muscles

• Bronchodilation, to increase the entrance of air into the lungs

• Hyperglycemia

• Inhibition of the digestive function

• Inhibition of the urinary and genital functions

In contrast, the activity of the parasympathetic system is related to protective and conservation functions, which favor the proper functioning of the different visceral organs. The functional components of the parasympathetic system do not act simultaneously under normal conditions, but participate in specific reflexes or in integrated reactions to promote a specific visceral function. Thus, stimulation of different nuclei of parasympatheti c neurons promotes responses such as:

• Pupillary constriction, to protect the retina from excessive illumination

• Decreased heart rate, to avoid excessive activity

• Bronchoconstriction, to protect the lungs

• Increased motility and digestive secretions, to promote digestion

• Urinary activity and urination

• Genital activity (erection)

Therefore, the parasympathetic effects are, in consonance with their fundamental purpose, more localized. In the parasympathetic ganglia, each preganglionic neuron contacts a few postganglionary neurons, whose divergence is much smaller than that of the sympathetic system [6].

Both efferent systems exert a control of the function of the visceral organs in variable forms. Some effector organs receive innervation from a single system. For example, the smooth muscle of most blood vessels is only controlled by sympathetic vasoconstrictor innervation (except for vessels of genital organs, which also receive parasympathetic innervation, and cholinergic vasodilator fibers in the skeletal muscles and brain). In these cases, control of the visceral activity depends on the variations of the frequency of discharge of the impulses by sympathetic innervation. As the autonomic nerves have a basal tonic activity (of low pulse frequencies, 0.5–5 Hz), the activity may increase or decrease. In most vessels, an increase in sympathetic frequency determines vasoconstriction and a decrease, vasodilation [7].

Sympathetic and parasympathetic nerve fibers simultaneously innervate many effector organs. The activity of the organ depends on the interaction or balance between the signals of both systems, which exert antagonistic effects. This interaction can be developed by opposite actions on the same effector cells, as in the heart, where the sympathetic excites the nodal cells thus increasing the heart rate, whereas the parasympathetic inhibits the same cells, thus reducing their frequency.

Another possibility is the action on different cells, with opposite effects. In the iris, the sympathetic excites the meridian muscular fibers, which produces mydriasis, whereas the parasympathetic excites the circular fibers and produces miosis. In these cases, the functional balance is relatively complex. In normal circumstances, the two systems are reciprocally active, because the central and reflex signals excite one system and inhibit the other. When both sympathetic and parasympathetic systems innervate the same target cells, more complex interactions arise. For example, the simultaneous activation of sympathetic fibers may exaggerate the cardiovascular response to parasympathetic activity and vice versa. This phenomenon is mediated by mutual influences at the presynaptic and postsynaptic domains [7].

There Are Functional Similarities in the Hierarchical Organization of the Autonomic and Somatic Motor Pathways

To understand the hierarchical organization of the ANS, several concepts derived from the somatic motor system are useful [3]. Any movement, even the simplest one, involves an enormous amount of information processing and the participation of numerous neuronal groups. On the other hand, each movement of our body is based on a posture; thus, it is important to consider how the motor system provides global responses for both components, the posture needed, and the movement itself.

To achieve this, there are four hierarchical levels in which the somatic motor system is organized (Fig. 1.1): (a) spinal cord; (b) brainstem; (c) motor cerebral cortex; (d) premotor cortical areas.

Fig. 1.1

Hierarchical organization of the somatic motor system . Modified with permission from Cardinali [3]

The circuits of the three basic motor reflexes, i.e., the myotatic reflex, the tendon reflex, and the withdrawal reflex, are found in the spinal cord, the centers of regulation of the dorsolateral and ventromedial motor neuron systems are located in the brainstem, and the motor programs defined by the secondary motor areas (premotor, motor supplemental area, parietal cortex) are situated in the primary motor cortex. Also, two other brain areas, the cerebellum and the basal ganglia, have an essential regulatory function with regard to the somatic motor system [3].

In the ANS, a similar arrangement can be found (Fig. 1.2). The four major levels are: (a) spinal cord; (b) brainstem; (c) hypothalamus; (d) limbic system.

Fig. 1.2

Hierarchical organization of the autonomic nervous system (ANS). The figure was prepared in part using image vectors from Servier Medical Art (www.servier.com), licensed under the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/license/by/3.0/)

The spinal cord contains connections that mediate segmental autonomic reflexes involved in visceral function. These localized autonomic phenomena acquire intersegmental significance in the brainstem. In the brainstem , many complex autonomic responses, such as cardiovascular and respiratory regulation, are found.

The other two hierarchical levels of the ANS organization are the hypothalamus and the limbic system. In the hypothalamus , autonomic motor programs acquire their homeostatic nature. The cardiocirculatory and respiratory response to hemorrhage is completed by a neuroendocrine response, i.e., the secretion of arginine vasopressin (AVP) and adrenocorticotropin (ACTH), and by a behavioral response (thirst and fluid intake, etc.). These neuroendocrine mechanisms have strong similarities to those of the somatic posture needed for the execution of orders derived from the top level of the motor system.

The limbic system gives the homeostatic reaction its emotional tone and social significance [8]. The amygdala provides affective or emotional value to incoming sensory information and has multiple downstream targets that participate in the autonomic and neuroendocrine–immune responses. The anterior cingulate cortex is interconnected with the anterior insula and is subdivided into the ventral and dorsal regions. The insular cortex is the primary interoceptive cortex that integrates visceral, pain, and temperature sensations. This hierarchical level also comprises the cerebellum , which participates in the coordination of the executed autonomic programs, and the basal ganglia, which are relevant for the selection of the autonomic program best adapted to a given situation [9].

It is useful to compare the performance of somatic and autonomic motor responses with that of a building under construction [3]. In this case, we can observe three basic categories, in hierarchical order: masons, foremen (overseers), and architects. Schematically, the architects are responsible for planning (activity before the start of the work), the foremen for the management and coordination, and the masons for the construction itself. All three functions are indispensable for building and the failure of one of them will affect the success of the whole work.

The main “architects” of the ANS, which are responsible for the layout of the autonomic programs, are in cortical and subcortical regions of the limbic system. They include the limbic association cortex and the subcortical areas such as the amygdala, hippocampus, septal nuclei, olfactory bulb, and portions of the basal ganglia (ventral striatum, nucleus accumbens). The ventral portion of the basal ganglia are part of a loop that begins and ends in the limbic areas. The limbic association cortex projects to ventral striatum (nucleus accumbens) then to the thalamus, and finally back to the limbic cortex. The overall function of this loop is to select a sequence of autonomic actions (behaviors) while suppressing others.

The “overseers” or areas of execution in the motor system are linked to the movement itself (dorsolateral system: primary motor cortex, red nucleus) and the posture (ventromedial system: vestibular nuclei, inferior colliculus superior, reticular formation) needed for that movement. In the case of the ANS, the hypothalamus plays such a function. The main autonomic behaviors coordinated by the hypothalamus are:

• Defense behavior

• Nutritive or appetitive behavior

• Thermoregulatory behavior

• Maternal and sexual behavior

Typically, autonomic behaviors involve the coordinated expression of autonomic, neuroendocrine, somatic, and motivational mechanisms. Recent observations underlined the role of the cerebellum in the appropriate coordination of these components [4].

The “masons” of the somatic motor system , which represent the final common pathway of the system and are directly responsible for muscle contraction, are: (a) the motor units of the spinal cord; (b) the motor units in the nuclei of the cranial nerves.

The “masons” of the ANS include the motor neurons (postganglionic) of the sympathetic, parasympathetic, and enteric systems. These neurons are separate functional units (vasomotor muscular, cutaneous vasomotor, sudomotor, pilomotor, visceromotor) that exercise a specific and appropriate control over a target organ or cell.

From data derived from the somatic motor system, there are three important aspects to be considered for the physiological understanding of the hierarchical organization described above: (a) there is somatotopy, i.e., an orderly anatomical map at each level of organization; (b) at each level of the motor system, information from the periphery is received and modifies the descending order of command; (c) the upper levels have the capacity to control or suppress the information that reaches them (afferent control).

For other authors, the hierarchical organization of the integrated control of autonomic responses involved in homeostasis, adaptation, and emotional and goal-oriented behaviors includes the following levels: (a) spinal; (b) bulbopontine; (c) pontomesencephalic; (d) forebrain [10]. The bulbopontine (lower brainstem) level is involved in the reflex control of circulation, respiration, gastrointestinal function, and micturition. The pontomesencephalic (upper brainstem) level integrates autonomic control with pain modulation and responses to stress. The brainstem autonomic areas include the periaqueductal gray, the parabrachial nucleus (PBN), the nucleus tractus solitarius (NTS), the ventrolateral medulla, and the medullary raphe. The forebrain regions involved in the control of autonomic functions include the insular cortex, the anterior cingulate cortex, the amygdala, and the hypothalamus.

However, such a view considers only partially the role of the hypothalamus as a central component in the ANS hierarchy. Maintaining the hypothalamus as an independent level has the advantage of recognizing its role in integrated autonomic, neuroendocrine–immune, and behavioral responses. Therefore, the areas of the central autonomic network: (a) are reciprocally interconnected; (b) receive converging visceral and somatosensory information; (c) generate stimulus-specific patterns of autonomic, endocrine, and motor responses; (d) are regulated according to the respective body configuration: wakefulness, slow wave or non-REM (NREM) sleep, REM sleep [3].

Fig. 1.3

Body posture is the position of the trunk relative to that of the limbs, and both, as a whole, in space. The postural reflexes are a set of antigravity reflexes, articulating with each other as a program. The postural adjustment includes anticipatory feed-forward programs and compensatory servo-assisted, feed-back mechanisms. In the same way, there is an “autonomic posture ” that includes the mechanisms of anticipatory predictive homeostasis and the corrective mechanisms of reactive homeostasis. Modified with permission from Cardinali [3]

The Autonomic Posture

The adjustment program of body posture includes compensatory and anticipatory mechanisms. The spinal motoneurons are under the continuous influence of descending impulses from the upper regions and from the corresponding muscular and skin territories. One of the fundamental descending programs regulating the activity of motoneurons is that of posture, derived from neurons located in the brainstem [11].

The term “posture” defines the position on the trunk and the limbs. The postural reflexes are a set of antigravity reflexes, articulating each other as a program. This postural adjustment program includes feed-back and feed-forward compensatory mechanisms (Fig. 1.3) In the same way, there is an “autonomic posture ” that includes the anticipatory mechanisms of predictive homeostasis and the corrective mechanisms of reactive homeostasis.

In the case of body posture, we anticipate with a proper body position the predictable changes given by muscle activity and the force of gravity, and correct this appropriate position with compensatory changes triggered by sensory information (Fig. 1.4). The position of the body in space varies accordingly to the movements performed. Therefore, we do not have a “single posture,” but the correct one that is adapted to the movements performed. This maintenance of the postural equilibrium requires, in addition to the movements, advanced programming, and an on-line regulation of the process to adapt to the changes. For this, the integration of four sensorial modalities is indispensable: (a) vision; (b) position of the head; (c) proprioception; (d) exteroception (touch). Based on these data, the nervous system produces an early postural program suitable for movement and provides a series of automatic adjustments if unanticipated problems occur (Fig. 1.4) [12].

Fig. 1.4

With any motor plan, the proper posture program is executed first. Note that postural responses are always triggered before voluntary movements (a). If a normal individual is placed on a forward-leaning platform, the extension of the lower limb stabilizes the body, which causes the extensor (antigravitational) reflex to increase in the lower limbs as it is practiced (b). If the platform is tilted backward, the extension of the lower members, antigravitational in the previous case, now produces destabilization. In this second case, and after a few repetitions of the test, the extensor reflex diminishes, until it is completely extinguished. There is strong evidence for the role of the cerebellum in the mechanisms of both body posture and autonomic posture. Modified with permission from Cardinali [3]

In the case of the autonomic posture , and as discussed in Chap. 2, the circadian system generates a map of acrophases (maximal neurovegetative functions controlled by the ANS) that allows the adequate neuroendocrine–immune configuration for each of the three autonomic configurations of the body to be anticipated in a 24-h cycle (wakefulness, NREM sleep, REM sleep) [3]. In the face of unexpected demands, the modification of the predetermined neuroendocrine–immune configuration and the readjustment of the autonomic function occur (Fig. 1.5).

Fig. 1.5

In the case of autonomic posture , the circadian system generates a map of acrophases (maximum neurovegetative functions controlled by the ANS), which allows the adequate neuroendocrine–immune configuration for each autonomic configurations of the body (wakefulness, slow wave sleep, REM sleep) (predictive homeostasis) to be anticipated. Based on interoception, when unexpected demands arise, the modification of the predetermined neuroendocrine–immune configuration and the readjustment of the autonomic function arise (reactive homeostasis). The figure was prepared in part using image vectors from Servier Medical Art (www.servier.com), licensed under the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/license/by/3.0/)

The neuroendocrine–immune mechanisms involved in the “autonomic posture ” are summarized in Fig. 1.6. The link between the activity of the nervous and immune systems has been the subject of numerous investigations in the last 50 years, giving rise to psychoneuroimmunoendocrinology as a discipline [13]. Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and nonhuman animal models. Neuroendocrine–immune interactions can be conceptualized using a series of feedback loops, which culminate in distinct neuroendocrine–immune phenotypes. Behavior can exert profound influences on these phenotypes, which in turn reciprocally modulate behavior [13].

Fig. 1.6

Basis of the autonomic posture . The way in which the nervous system communicates with the immune system is twofold: (a) through the neuroendocrine system (hypothalamic–pituitary axis and pineal gland), via the secretion of pituitary, adrenocortical, thyroid and gonadal hormones and melatonin, thus modulating the immune response; (b) through the ANS, in both the parasympathetic and sympathetic divisions, which supplies the lymph nodes, thymus, spleen, and bone marrow. Various groups of hypothalamic neurons react to humoral signals (cytokines) produced by immunocompetent cells

The way in which the nervous system communicates with the immune system is twofold: (a) through the neuroendocrine apparatus (hypothalamic–pituitary axis and pineal gland), via the secretion of pituitary, adrenocortical, thyroid, and gonadal hormones, and melatonin, all of which have a modulatory effect on the immune response; (b) through the ANS, both the sympathetic and parasympathetic divisions, which innervates the lymph nodes, thymus, spleen, and bone marrow (Fig. 1.6). Both pathways carry the link among the limbic, motivational, and immune response. Galen (second century AD), in his writings “On tumors against nature,” had sensed this association, stating that breast cancer appeared in women whose menstruation was either abnormal or nonexistent because of the accumulation of “waste of black bile” (melancholia). A depressed patient is prone to developing inadequate immune responses; in contrast, a normal emotional balance contributes to a normal immune defense.

On the other hand, and because of the immune reaction, important changes in neuronal activity are verifiable. Several groups of central neurons react to humoral signals produced by immunocompetent cells (cytokines), such as interleukin (IL) 1 and 6, tumor necrosis factor-α (TNF-α), or interferon-γ (IFN-γ) [13]. These cytokines give rise to signs and symptoms that accompany acute or chronic infection (loss of appetite or anorexia, depressed motor activity, loss of interest in daily activities), in addition to activating the adrenal pituitary axis and producing thermogenesis (disease behavior).

The ambiome is defined as the set of nongenetic, changing elements that surround the individual and that contribute to the development and building of the human being, and therefore the state of health or the appearance of disease. It is part of the biopsychosocial–ecological reality of the individual from which the microbiome has been extracted as being very important in recent years. The microbiome defines the set of microorganisms that are normally located in different places in the human body, in particular the digestive tract [14]. The microbiome is in a commensal symbiotic relationship with the host. These microbial components aid in the digestion of food, produce vitamins, and protect against the colonization of other microorganisms that may be pathogenic. There are few physiological and immunological parameters that are not deeply affected by the presence and nature of the microbiome, with host resistance to infections being one of the most prominent factors. The gut microbiome is highly dynamic, exhibiting daily cyclic fluctuations that have repercussions for the host metabolism and provide evidence for the cross-regulation of prokaryotic and eukaryotic circadian rhythms [14]. We could see the microbiome forming part of our internal environment.

Genetic factors explain only some (<30%) of the changes linked to health and disease, as revealed by studies in twins. The ambiome and the microbiome correspond to the rest of the changes, which are essentially epigenetic. The biopsychosocial–ecological nature of the individual changes in the three autonomic body configurations, wakefulness, slow-wave sleep, and REM sleep is discussed in Chap. 2. Therefore, the autonomic posture is an essential and prior program for the homeostatic responses of organs and systems [15].

Hence, rather than being a mere top–down or reflex regulation, signals from the organs influence the functioning of the brain. For example, the reflex regulation of BP and the heart rate is not only subject to modulation by ascending information from the body, but also by descending information from several areas in the hypothalamus and cortex. The CNS has the capacity to control its output via the ANS using an amazing differentiation. For example, not only do the biological clock and prefrontal cortex contain neurons that influence the parasympathetic or sympathetic motor neurons, they also contain different neurons that project to diverse body compartments.

In the end, this leads to integrated responses whereby visceral sensory information reaches higher centers in the CNS via vagal or spinal sensory pathways, causing a reaction that considers factors such as the time of day, the season, the reproductive status, or the mood. Based on all this information, the brain sets the balance of the different parts of the ANS, causing its output to change its emphasis as per the situation. A disturbed balance, either as a result of behavior or of disease of any of the organs, leads to pathological conditions affecting the functioning of the entire individual [15].

Basic Neuronal Organization of ANS

Although dozens of types of neurons have been described in the nervous system by their morphological characteristics, when the length of the axon (indicative of the function they play) is considered, only two types of neurons are distinguished (Fig. 1.7) [3]:

• Golgi type I neurons with an identifiable axon, which are involved in the transfer of information between brain regions or in providing a basal tone of excitation to widespread brain areas. The difference between the two subsets of Golgi I neurons is the degree of axonal branching. In projection neurons, ramifications are limited to one or a few brain areas, whereas in widely distributed neurons (“spider web” neurons), axonal arborization ends in many areas or in some cases most of the cerebral cortex.

• Golgi type II neurons , with no identifiable or poor developed axon, that fulfill the function of interneurons in local circuits.

Fig. 1.7

Golgi type I (a) and Golgi type II neurons (b). Modified with permission from Cardinali [3]

These two neuronal types (Golgi I and Golgi II) generate the three basic circuits:

• Local circuits, consisting of interneurons.

• Projection circuits or “point to point” connections, which relate to distant local circuits between them.

• “Spider web” circuits , by which local modifications of brainstem nuclei are transformed into global states of CNS, e.g., wakefulness or sleep. These circuits are of fundamental importance for understanding the homeostatic function of the ANS.

Synaptic potentials are how a neuron can modify the membrane potential of the cells with which it connects. For this, the presynaptic neuron releases a chemical transmitter or, less frequently, the transmission is performed by an electrical mechanism [11].

In chemical transmission, the neurotransmitter interacts with receptors on the surface of the postsynaptic membrane resulting in the generation of synaptic potentials, which may be inhibitory – inhibitory postsynaptic potential (IPSP ; i.e., of a hyperpolarizing nature) – or excitatory – excitatory postsynaptic potential (EPSP ; i.e., of a depolarizing nature). The duration of synaptic potentials varies from a few milliseconds to, in some cases, seconds, or minutes (Fig. 1.8). These potentials are local and summable.

Fig. 1.8

The different signals of reception, integration, conduction, and secretion in neurons (left).The different electric potentials found in each segment (right). Modified from Cardinali [3]

The integration signal (Fig. 1.8) is observed in the “trigger area” of the neuronal membrane, where various local potentials, propagated electrotonically, are summed, giving rise to the action potential. Generally, but not always, the “trigger zone” is in the axonal cone. This area is characterized by a high concentration of Na⁺- and K⁺-dependent voltage channels and constitutes the lowest threshold portion of the entire cell membrane. If the sum of the synaptic potentials reaches the threshold, an action potential is generated; hence, the signal produced is called “integrative” [11].

The driving signal is the action potential (Fig. 1.8). Whereas receptor synaptic potentials only passively propagate with sharp decreases in amplitude as a function of distance, the action potential (or “spike potential”) has the following properties: (a) it actively propagates along the axons or in certain cases, as the pyramidal neurons of the cerebral cortex, also in dendrites; (b) it does not diminish its intensity as a function of distance; (c) it is of an “all or nothing” nature; (d) it is similar in all neurons, regardless of the neuron’s function. The action potential amplitude is approximately 100 mV and the duration potential is 0.5–2 ms.

Although the Na⁺-dependent action potential is the fastest method of signal conduction in the CNS, in the dendrites of the central neurons there are Ca²⁺ voltage channels displaying most of the properties of the Na⁺ action potential. The main difference is the amplitude, i.e., a few mV for Ca²⁺ action potential vs 100 mV of Na⁺ action potential.

The output signal (Fig. 1.8) is observed in synaptic axon terminals, where depolarization causes the release of neurotransmitter (chemical type synapses) or disturbs the resting potential of the postsynaptic neuron (electric type synapses) owing to the apposition of the membranes. In the case of chemical synapses, transmitter release depends on the entry of Ca²⁺ and involves the generation of a secretory potential [11].

Based on their conduction velocity (Fig. 1.9), nerve fibers are generally classified into:

• A fibers, myelinated, 2–20 mm thick with a velocity of 15–120 m/s. They are the sensory or motor fibers found in the somatic nerves. They comprise four subgroups, from highest to lowest speed: α, β, γ, δ. In the ANS the A fibers found are Aδ.

• B fibers, myelinated, 1–3 mm thick with a velocity of 3–15 m/s. They constitute the white communicating branches (preganglionic afferents) of the sympathetic chain.

• C fibers, unmyelinated, <1 mm thick, with a velocity of <2 m/s. They are the afferent amyelinic fibers of the visceral nerves and the sympathetic postganglionic nerves.

Fig. 1.9

Compound action potential in a peripheral nerve with peaks generated by different types of nerve fibers. Modified from Cardinali [3]