7
I. OVERVIEW
Cells erect a barrier around themselves (the plasma membrane) to create and maintain an internal environment that is optimized to suit their metabolic needs. The body similarly is covered with the skin to establish an internal environment whose temperature, pH, and electrolyte levels are optimized for tissue function. Maintaining a stable internal environment (i.e., homeostasis) is the responsibility of the autonomic nervous system (ANS). The ANS is organized similarly to the somatic nervous system and uses many of the same neural pathways. Internal sensory receptors gather information about blood pressure (baroreceptors), blood chemistry (chemoreceptors), and body temperature (thermoreceptors) and relay it to autonomic control centers in the brain. The control centers contain neural circuits that compare incoming sensory data with internal preset values. If comparators detect a deviation from the presets, they adjust the function of one or more organs to maintain homeostasis. The principal organs of homeostasis include the skin, liver, lungs, heart, and kidneys (Figure 7.1). The ANS modulates organ function via two distinct effector pathways: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PSNS). The actions of the SNS and PSNS often appear antagonistic, but, in practice, they work in close cooperation with each other.
II. HOMEOSTASIS
The term “homeostasis” refers to a state of physiologic equilibrium or the processes that sustain such an equilibrium. An individual must maintain homeostatic control over numerous vital parameters to survive and thrive, including arterial PO2, blood pressure, and extracellular fluid osmolality (see Figure 7.1). Losing control over one or more of these parameters manifests as illness and usually prompts a patient to seek medical attention. It is a physician's task to identify the underlying cause of the imbalance and intervene to help restore homeostasis.
A. Mechanisms
Homeostatic control pathways are seen at both the cellular and organismal level, and they all include at least three basic components that typically form a negative feedback control system (Figure 7.2). There is a sensory component (e.g., a receptor protein) that detects and relays information about the parameter subject to homeostatic control, an integrator (e.g., a neural circuit) that compares incoming sensory data with a system preset value, and an effector component capable of changing the regulated variable (e.g., an ion pump or excretory organ). For example, a rise in arterial PCO2 is sensed by chemoreceptors that feed information to a respiratory control center in the brainstem. The control center responds by increasing respiration rate to expel the excess CO2. Conversely, a decrease in PCO2 reduces respiration rate. Homeostasis may also involve a behavioral component. Behavior drives intake of salt (NaCl), water, and other nutrients and, for example, impels one to turn on air conditioning or shed clothing if body temperature is too high.
Figure 7.1
Principal homeostatic organs.
Figure 7.2
Negative feedback control of PCO2. CNS = central nervous system.
B. Redundancy
Homeostasis at the organismal level typically involves multiple control pathways that are layered and often hierarchical, with the number of layers reflecting the relative importance of the parameter under control. Blood pressure, for example, is controlled by numerous local and central regulatory pathways. Layering creates redundancy, but it also ensures that if one pathway fails, one or more redundant pathways can assert control to ensure continued homeostasis. Layering also allows a very fine degree of homeostatic control.
C. Functional reserve
Organ systems that are responsible for homeostasis typically have considerable functional reserve. For example, normal quiet breathing uses only ~10% of total lung capacity, and cardiac output at rest is ~20% of maximal attainable values. Reserves allow the lungs to maintain arterial PO2 and the heart to maintain blood pressure at optimal levels even as body activity level and demand for O2 and blood flow increases (e.g., during exercise). Functional reserve also allows for progressive decreases in functional capacity, such as occurs with age and disease (see 40·II·A).
III. ORGANIZATION
The ANS, also known as the visceral nervous system, is responsible for maintaining numerous vital parameters. Homeostasis must continue when we sleep or our conscious minds are focused on a task at hand, so the ANS operates subconsciously and largely independently of voluntary control. Exceptions include the voluntary interruption of breathing to allow for talking, for example. The ANS is organized along similar principles to those of the somatic motor system. Sensory information is relayed via afferent nerves to the central nervous system (CNS) for processing. Adjustments to organ function are signaled via nerve efferents. The main differences between the two systems relate to efferent arm organization. The ANS employs a two-step pathway in which efferent signals are relayed through ganglia (Figure 7.3).
A. Afferent pathways
ANS sensory afferents relay information from receptors that monitor many aspects of body function, including blood pressure (baroreceptors); blood chemistry, that is, glucose levels, pH, PO2, and PCO2(chemoreceptors); skin temperature (thermoreceptors); and mechanical distension of the lungs, bladder, and gastrointestinal (GI) system (mechanoreceptors). Sensory afferent fibers often travel in the same nerves as do autonomic and somatic efferents. Autonomic nerves also contain nociceptive fibers, which provide for visceral pain sensation.
B. Efferent pathways
In the somatic motor system, motor neuron cell bodies originate within the CNS (see Figure 7.3). In the ANS, the cell bodies of motor efferents are contained within ganglia, which lie outside the CNS, often in close proximity to their target organs (Figure 7.4; also see Figure 7.3).
1. Autonomic ganglia: Ganglia comprise clusters of nerve cell bodies and their dendritic trees. Commands originating in the CNS are carried to ganglia by myelinated preganglionic neurons. Unmyelinated postganglionic neurons relay the commands to the target tissues.
a. Sympathetic: Sympathetic ganglia are located close to the spinal cord. Therefore, sympathetic preganglionic neurons are relatively short. Postganglionic neurons are relatively long, reflecting the distance between the ganglia and the target cells. There are two types of sympathetic ganglia. Paravertebral ganglia are arranged in two parallel sympathetic chains located to either side of the vertebral column. The ganglia within the chains are linked by neurons that run longitudinally, which allows signals to be relayed vertically within the chains as well as peripherally. Prevertebral ganglia are located in the abdominal cavity.
b. Parasympathetic: Parasympathetic ganglia are located in the periphery near or within the target organ. Thus, parasympathetic preganglionic neurons are much longer than the postganglionic neurons.
2. Sympathetic efferents: The cell bodies of sympathetic preganglionic neurons are located in nuclei contained within upper regions of the spinal cord (T1–L3). Neurons located rostrally regulate the upper regions of the body, including the eye, whereas caudal neurons control the function of lower organs, such as the bladder and genitals. Preganglionic neurons leave the spinal cord via a ventral root, enter a nearby paravertebral ganglion, and then terminate in one of several possible locations:
• within the paravertebral ganglion;
• within a more distant sympathetic chain ganglion; or
• within a prevertebral ganglion, a more distal ganglion, or the adrenal medulla.
3. Parasympathetic efferents: Preganglionic neurons of the PSNS originate in brainstem nuclei or in the sacral region of the spinal cord (S2–S4). Their axons leave the CNS via cranial or pelvic splanchnic nerves, respectively, and terminate within remote ganglia located close to or within the walls of their target organs.
Figure 7.3
Somatic and autonomic nervous system efferent pathways.
Figure 7.4
Autonomic nervous system organization. CN = cranial nerve.
IV. NEUROTRANSMISSON
The differences between the somatic motor system and the ANS become more apparent when transmitters and synaptic structure are reviewed (Figure 7.5).
A. Preganglionic transmitters
All ANS preganglionic neurons (SNS and PSNS) release acetylcholine (ACh) at their synapses. The postsynaptic membrane bears nicotinic ACh receptors (nAChRs), which mediate Na+ influx and membrane depolarization when activated, as in skeletal muscle. However, whereas skeletal muscle expresses an N1-type AChR, ANS preganglionic cell bodies and chromaffin cells in the adrenal medulla express an N2-type AChR.
N1- and N2-type AChRs have different sensitivities to nAChR antagonists, which makes it possible to inhibit the entire ANS output while leaving the skeletal musculature unaffected, or vice versa.1Pancuronium is an N1-type receptor antagonist used in general anesthesia to relax skeletal muscle and aid intubation prior to surgery. It has relatively minor effects on ANS function. Conversely, trimethaphan is an N2-type antagonist that blocks both arms of the ANS while having little effect on the skeletal musculature.
B. Postganglionic transmitters
Somatic motor neurons act through an ionotropic nAChR and are always excitatory. In contrast, ANS effector neurons communicate with their target cells via G protein–coupled receptors and, thus, may have an array of consequences.
1. Parasympathetic: All PSNS postganglionic neurons release ACh from their terminals. Target cells express M1- (salivary glands, stomach), M2- (cardiac nodal cells), or M3-type (smooth muscle, many glands) muscarinic AChRs (see Table 5.3).
2. Sympathetic: Most SNS postganglionic neurons release norepinephrine from their terminals. Target cells may express α1-(smooth muscle); β1- (cardiac muscle); β2- (smooth muscle); or, less commonly, α2- (synaptic terminals) adrenergic receptors (see Table 5.3). The exceptions are the SNS efferents that regulate eccrine sweat glands, which release ACh at their terminals and act through an M3-type AChR (see 16·VI·C·2).
Figure 7.5
Autonomic nervous system neurotransmitters. ACh = acetylcholine; M1 AChR, M2 AChR, and M3 AChR = muscarinic ACh receptors; N1 and N2 AChR = nicotinic ACh receptors.
1For a more complete discussion of cholinergic antagonists and their actions, see LIR Pharmacology, 5e, Chapter 5.
C. Postganglionic synapses
Somatic motor nerves terminate at highly organized neuromuscular junctions. The site of synaptic contact between an ANS neuron and its target cell is very different. Many postganglionic nerve axons exhibit a string of beadlike varicosities (swellings) in the region of their target cells (Figure 7.6). Each represents a site of transmitter synthesis, storage, and release, functioning as a nerve terminal.
V. EFFECTOR ORGANS
The somatic motor system innervates skeletal musculature. The ANS innervates all other organs. Most visceral organs are innervated by both arms of the ANS. Although the two divisions typically have opposite effects on organ function, they usually work in a complementary rather than antagonistic fashion. Thus, when sympathetic activity increases, output from the parasympathetic division is withdrawn and vice versa. The principal targets and effects of ANS control are summarized in Figures 7.1 and 7.4.
Figure 7.6
Autonomic nerve varicosities.
VI. BRAINSTEM
ANS output can be influenced by many higher brain regions, but the main areas involved in autonomic control include the brainstem, the hypothalamus, and the limbic system. The relationship between these areas is shown in Figure 7.7. The brainstem is the primary ANS control center and can maintain most autonomic functions for several years even after clinical brain death has occurred (see 40·II·C). The brainstem comprises nerve tracts and nuclei. The nerve tracts convey information between the CNS and the periphery. Nuclei are clusters of nerve cell bodies, many of which are involved in autonomic control.
A. Preganglionic nuclei
Preganglionic nuclei are the CNS equivalents of ganglia, comprising clusters of nerve cell bodies at the head of one or more cranial nerves (CNs). Nuclei usually also contain interneurons that create simple negative feedback circuits between afferent and efferent nerve activity. Such circuits mediate many autonomic reflexes, such as reflex slowing of heart rate when blood pressure is too high and receptive relaxation of the stomach when it fills with food (see Clinical Application 7.1). The brainstem contains several important PSNS preganglionic nuclei, including the Edinger- Westphal nucleus, superior and inferior salivatory nuclei, the dorsal motor nucleus of vagus, and the nucleus ambiguus (Figure 7.8). The nucleus ambiguus contains both glossopharyngeal (CN IX) and vagal (CN X) efferents that innervate the pharynx, larynx, and part of the esophagus. The nucleus helps coordinate swallowing reflexes, and it also contains vagal cardioinhibitory preganglionic fibers.
B. Nucleus tractus solitarius
The nucleus tractus solitarius (NTS) is a nerve tract running the length of the medulla through the center of the solitary nucleus (see Figure 7.8) that coordinates many autonomic functions and reflexes. It receives sensory data from most visceral regions via the vagus and glossopharyngeal nerves (CNs IX and X) and then relays this information to the hypothalamus. It also contains intrinsic circuits that facilitate local (brainstem) reflexes controlling respiration rate and blood pressure, for example.
Figure 7.7
Autonomic control centers. ANS = autonomic nervous system.
Clinical Application 7.1: Autonomic Dysfunction
Disruption of autonomic pathways can result in specific functional deficits or more generalized loss of homeostatic function, depending on the nature of the underlying pathology. Horner syndrome is caused by disruption of the sympathetic pathway that raises the eyelid, controls pupil diameter, and regulates facial sweat gland activity. The result is a unilateral ptosis (drooping eyelid), miosis (inability to increase pupil diameter), and local anhidrosis(inability to sweat). More generalized autonomic dysfunctions are common among patients on maintenance dialysis and those with diabetes whose glucose levels are poorly controlled (diabetic autonomic neuropathy, or DAN). DAN can manifest as an inability to control blood pressure following a meal (postprandial hypotension) or upon standing (postural hypotension), gastrointestinal motility disorders (difficulty swallowing and constipation), or bladder dysfunction, among other symptoms.
Tests designed to assess autonomic function include monitoring cardiac responses during changes in posture, hand immersion in ice water (the cold pressor test, designed to induce intense pain), and a Valsalva maneuver.
A Valsalva maneuver involves forced expiration against a resistance, designed to cause intrathoracic pressures to rise to 40 mm Hg for 10–20 s. The pressure increase prevents venous blood from entering the thorax, so cardiac filling is impeded, and arterial pressure falls. In a healthy individual, a fall in arterial pressure is sensed by arterial baroreceptors, initiating a reflex increase in heart rate that is mediated by sympathetic efferents traveling in the vagus nerve. Patients with DAN may have impaired baroreceptor or vagal nerve function and, thus, fail to respond to a Valsalva maneuver with the expected tachycardia.
Figure 7.8
Principal autonomic brainstem nuclei. CN = cranial nerve; GI = gastrointestinal.
C. Reticular formation
The reticular formation comprises a collection of brainstem nuclei with diverse functions, including control of blood pressure and respiration (as well as sleep, pain, motor control, etc.). It receives sensory data from the glossopharyngeal and vagal nerves and helps integrate it with effector commands from higher autonomic control centers located in the limbic system and hypothalamus.
D. Control centers
Brainstem areas that have related functions are considered control centers, even if separated spatially. Brainstem control centers include the respiratory center, cardiovascular control center, and micturition center (Table 7.1).
VII. HYPOTHALAMUS
The hypothalamus establishes the set point for many internal parameters, including body temperature (37°C), mean arterial pressure (~95 mm Hg), and extracellular fluid osmolality (~290 mOsm/kg). Its influence extends to virtually all of the body's internal systems, belying its tiny size (~4 cm3, or ~0.3% of brain volume). The ability to establish a set point or narrow operating range minimally requires that the hypothalamus be provided with a way of monitoring the parameters it controls and a way of communicating with the organs that maintain them.
A. Organization
The hypothalamus is located below the thalamus at the base of the brain. It contains several distinct nuclei summarized in Figure 7.9. Note that although some of these nuclei have clearly defined functions, others are organized in functional groups or areas that work cooperatively. In addition to controlling autonomic functions, the hypothalamus can stimulate many behavioral responses, including those associated with sexual drive, hunger, and thirst.
B. Neural pathways
The hypothalamus receives reciprocal innervation from many areas, as might be expected of such a key integrative organ. The major pathways for information flow occur between the hypothalamus and the brainstem as well as the hypothalamus and the limbic system (see Figure 7.7).
Figure 7.9
Hypothalamic nuclei. ADH = antidiuretic hormone.
C. Circumventricular organs
Any organ that is tasked with maintaining homeostasis needs to be able to monitor the parameters that it controls. In the case of the hypothalamus, this includes ions, metabolites, and hormones. The hypothalamus is a part of the brain, however, meaning that it is isolated from most such factors by the blood–brain barrier (BBB). Although it does receive feedback from peripheral receptors, the information they provide is limited. Therefore, the hypothalamus is provided with windows in the BBB through which it can make observations about blood composition directly. These windows are called circumventricular organs (CVOs).
1. Location: The brain contains six CVOs (Figure 7.10). CVOs comprise specialized brain regions where the BBB is interrupted to allow cerebral neurons to interact with the circulation directly. Some CVOs are sensory, whereas others are secretory.
a. Sensory: Sensory CVOs include the subfornical organ and the organum vasculosum of the lamina terminalis, both associated with the hypothalamus. The area postrema is a brainstem CVO.
b. Secretory: Secretory CVOs include the median eminence (part of the hypothalamus), the neurohypophysis (posterior pituitary gland), and the pineal gland.
2. Structure: CVOs are designed as interfaces between the brain and the periphery. They are highly vascularized, and blood flows through these regions slowly to maximize time available for exchanging materials between blood and brain. Also, CVO capillaries are fenestrated and leaky, which facilitates movement of ions and smaller proteins between blood and interstitium.
3. Sensory functions: Sensory CVOs contain neuronal cell bodies that are sensitive to numerous bloodborne factors (Na+, Ca2+, angiotensin II, antidiuretic hormone, natriuretic peptides, sex hormones, and feeding and satiety signals). Their axons project to hypothalamic areas that control corresponding variables.
D. Endocrine functions
Most organs in the body are dually regulated by the nervous system and the endocrine system. The hypothalamus's key homeostatic role requires that it be able to influence both systems. It modulates the neural component via nerve tracts and peripheral nerves. It exerts endocrine control using hormones (summarized in Tables 7.2 and 7.3) that are released via the pituitary gland.
1. Endocrine axes: The hypothalamus, pituitary, and a dependent endocrine gland together form a unified control system known as an endocrine axis. Most endocrine systems are organized into such axes. The advantage of this system is that it allows for both fine and gross control of hormone output. For example, the hypothalamic–pituitary–adrenal axis regulates cortisol secretion from the adrenal cortex. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary. ACTH stimulates cortisol production by the adrenal cortex. Cortisol exerts negative feedback control on both ACTH production by the anterior pituitary, and both ACTH and cortisol inhibit CRH synthesis by the hypothalamus.
Figure 7.10
Circumventricular organs.
2. Pituitary gland: The pituitary gland (also known as the hypophysis) projects from the hypothalamus at the base of the brain and nestles in a bony cavity called the sella turcica (Latin for “Turkish saddle”). The hypothalamus and pituitary are connected by the pituitary (or hypophyseal) stalk, which contains bundles of neurosecretory axons. The pituitary contains two lobes (Figure 7.11). Although they lie next to each other within a common gland, they have very different embryologic origins and cellular compositions.
a. Anterior lobe: The anterior lobe (adenohypophysis) has epithelial origins. It comprises a collection of glandular tissues that synthesize and store hormones (see Table 7.2). Hormone release is regulated by the hypothalamus using hormone-releasing or release-inhibiting hormones, which travel from hypothalamus to the anterior pituitary via the hypophyseal portal system (see below).
b. Hypophyseal portal system: The hypophyseal portal system directs blood from the hypothalamus to the anterior lobe of the pituitary gland (see Figure 7.11). This unusual serial vascular arrangement is used to carry peptide hormones synthesized by hypothalamic parvocellular (small-cell) neurosecretory cells to the anterior pituitary, where they stimulate or inhibit pituitary hormone release. Hypothalamic hormones are synthesized in neurosecretory cell bodies and then transported down their axons to terminals located in the median eminence. The median eminence is a CVO that sits at the head of the pituitary stalk and its portal system. Given an appropriate stimulus, the hormones are released from the nerve terminals into the portal system and carried to the capillaries supplying the anterior lobe's hormone-secreting cells.
Figure 7.11
Anterior pituitary.
c. Posterior lobe: The posterior lobe (neurohypophysis) is neural tissue. Axons from magnocellular (large-cell) neurosecretory cells in the supraoptic and paraventricular nuclei extend down the pituitary stalk and terminate within a CVO located in the posterior lobe (Figure 7.12). Magnocellular cell bodies synthesize oxytocin (OT) and antidiuretic hormone (ADH), two related peptide hormones (see Table 7.3). The hormones are transported to the nerve terminals via the pituitary stalk and stored in secretory granules (Herring bodies) awaiting release. The posterior pituitary is highly vascular and the capillaries fenestrated. When peptides are released, they enter the general circulation directly.
Figure 7.12
Posterior pituitary.
3. Anterior pituitary hormones: The anterior pituitary comprises five endocrine cell types (Table 7.4). The hormones they produce can be placed in one of three structurally related groups.
a. Adrenocorticotropic hormone: ACTH (corticotropin) is synthesized by corticotropes as a preprohormone, that is, preproopiomelanocortin (prePOMC). Removing the signal sequence yields POMC, a 241 amino acid–peptide containing ACTH (39 amino acids), melanocyte-stimulating hormone (MSH), and β endorphin (an endogenous opioid). Corticotropes lack the enzymes necessary to generate MSH or β-endorphin, however, so they release ACTH alone.
b. Glycoprotein hormones: Thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are related glycoproteins. All three hormones are heterodimers that share a common α subunit called α-glycoprotein subunit (α-GSU) and a hormone-specific β subunit. TSH is synthesized in thyrotropes and comprises a α-GSU–β-TSH dimer. FSH and LH are released by gonadotropes and comprise α-GSU–β-FSH and α-GSU–β-LH dimers, respectively. Human chorionic gonadotropin (hCG) is a related placental hormone comprising an α-GSU–β-hCG heterodimer.
c. Growth hormone and prolactin: Growth hormone (GH) and prolactin are related polypeptides synthesized by somatotropes and lactotropes, respectively. A related hormone, human placental lactogen, is synthesized by the fetal placenta. GH is a single-chain, 191 amino acid–residue polypeptide synthesized and released in several different isoforms. Prolactin, a 199 amino acid–polypeptide, is the only anterior pituitary hormone whose release is under tonic inhibition by the hypothalamus (via dopamine).
4. Posterior pituitary hormones: OT and ADH are near- identical nonapeptide hormones (they differ at only two amino acid positions) with a common evolutionary ancestor (Figure 7.13). They are both synthesized as preprohormones that contain a signal peptide, the hormone, a neurophysin, and a glycoprotein. The signal peptide and glycoproteins are removed to form prohormones during processing and packaging in the Golgi apparatus. Prooxyphysin comprises OT and neurophysin I, whereas propressophysin comprises ADH and neurophysin II. The hormones are separated by proteolysis from their respective neurophysins after packaging in neurosecretory vesicles and fast axonal transport to the posterior pituitary. The neurophysins (and glycoproteins) are coreleased along with hormone but have no known physiologic function.
The structural similarities between OT and ADH causes some functional crossover when circulating hormone levels are sufficiently high. Thus, OT can have mild antidiuretic effects, whereas ADH can cause milk ejection in lactating women.
Figure 7.13
Structural similarities between posterior pituitary hormones.
E. Clock functions
Most bodily functions, including body temperature, blood pressure, and digestion, have daily (“circadian,” derived from the Latin circa dies) rhythms. All cells appear capable of generating such self-sustaining rhythms. The hypothalamus synchronizes these rhythms and entrains them to a circadian cycle established by a master clock. Entrainment allows the body's various physiologic functions to be modified to anticipate coming nightfall or daybreak and optimized to coincide with a sleep–wake cycle. The master clock is located in the suprachiasmatic nucleus (SCN). It synchronizes bodily functions in part through the endocrine system, with the pineal glandacting as a neuroendocrine intermediary.
1. Molecular clocks: Although many cortical regions contain circuits that establish seasonal and other rhythms, the master clock responsible for circadian rhythms resides in the SCN (see Figure 7.9). The molecular cogs that make the clock run comprise two sets of genes locked in a negative feedback control system (Figure 7.14). CLOCK gene proteins promote transcription of CRY and PER genes, whose translation products inhibit CLOCK gene transcription. The transcription–translation cycle oscillates over a period of ~24 hr.
2. Setting the time: Although the master clock oscillates with an inherent periodicity of around 24 hr, the clock is reset daily to entrain it to the light–dark cycle. The clock is set by light falling on a small subset of retinal ganglion cells (~1%–3% of total). These cells express melanopsin, a photopigment that allows them to detect and respond to light. Signals from these cells reach the hypothalamus via afferents traveling in the retinohypothalamic tract of the optic nerve (Figure 7.15).
Figure 7.14
The master clock.
3. Pineal gland: The SCN synchronizes body functions in part through manipulation of endocrine axes using the pineal gland as an intermediary. The pineal gland is a small (~8 mm) pineconeshaped (hence the name) gland located at the midline near the posterior wall of the third ventricle (see Figure 7.10). It comprises pinealocytes and glial support cells that are similar to pituicytes (pituitary glial cells). The SCN communicates with the pineal gland via neural connections to the brainstem and spinal cord, and from there via sympathetic connections to the superior cervical ganglion and pineal gland. The pineal gland is a secretory CVO, which allows melatonin to be released into the circulation directly.
4. Melatonin: Melatonin is an indoleamine (N-acetyl-5-methoxytryptamine) synthesized from tryptophan. The synthetic pathway includes arylalkylamine N-acetyltransferase (AA-NAT), which is regulated by the SCN via adrenergic inputs from the SNS. When light falls on the retina, the sympathetic pathways from the SCN to the pineal gland are activated, and AA-NAT activity is inhibited (see Figure 7.15). Melatonin synthesis and secretion fall, as a result, and do not resume until dark (Figure 7.16).
Individuals with Smith-Magenis syndrome (a developmental disorder) have an inverted melatonin secretory response to light. Melatonin levels peak during the daytime and fall at night. These patients have neurobehavioral problems and sleep disturbances, underscoring melatonin's importance in timing CNS function.
VIII. LIMBIC SYSTEM
The limbic system comprises a collection of functionally related nuclei encircling the brainstem (hippocampus, cingulate cortex, and anterior thalamic nuclei) that strongly influence autonomic activity via connections to the hypothalamus. Many of these nuclei control emotions and motivational drives. These connections explain how emotions such as rage, aggression, fear, and stress can so profoundly exert physiologic effects. Everyone is familiar with the sensations associated with fright: a rapid, pounding heartbeat (increased heart rate and myocardial contractility; rapid breathing (respiratory center); cold, sweaty palms (sympathetic activation of sweat glands); and hairs standing erect on the back of the neck (piloerection).
Figure 7.15
Effects of light on melatonin release.
Figure 7.16
Melatonin effects on physiologic function.
Chapter Summary
• The central nervous system comprises the somatic nervous system and autonomic nervous system (ANS). The somatic nervous system controls skeletal musculature, whereas the ANS controls visceral organ function. The ANS's primary function is to maintain internal homeostasis.
• The autonomic nervous system (ANS) operates subconsciously and largely independently of voluntary control. The ANS incorporates two functionally distinct effector pathways (sympathetic and parasympathetic) that act cooperatively and in a reciprocal fashion to ensure homeostasis.
• The autonomic nervous system receives sensory information from receptors located throughout the body that monitor blood pressure, chemistry, and body temperature. This information is used to modify effector function via local reflexes or higher (central) autonomic control centers.
• Effector commands are relayed from autonomic control centers via ganglia that lie outside of the central nervous system. Sympathetic ganglia lie close to the spinal cord, whereas parasympathetic ganglia are located close to or within the walls of their target organs. All preganglionic neurons and parasympathetic effectors release acetylcholine at their terminals. Most sympathetic postganglionic motor neurons are adrenergic and release norepinephrineat target organs.
• Principal autonomic control centers include the brainstem and hypothalamus.
• The brainstem contains multiple autonomic control nuclei and control centers. The nucleus tractus solitarius and reticular formation help integrate autonomic sensory information with effector commands from the hypothalamus and limbic system.
• The hypothalamus establishes the set point for many vital internal parameters. It exerts homeostatic control through modification of brainstem control pathways and hormonally via the pituitary gland.
• The pituitary gland has two lobes: one comprising epithelial glandular tissue (anterior lobe), the other neural tissue (posterior lobe). Two breaches in the blood–brain barrier (circumventricular organs) allow pituitary hormones to be deposited into the general circulation.
• The hypothalamus stimulates release of six peptide (tropic) hormones from the anterior lobe into the circulation using release-stimulating or release-inhibiting hormones. These hypothalamic hormones reach the pituitary via the hypophyseal portal system. Two additional hormones are released from hypothalamic nerve terminals located in the posterior pituitary.
• Sensory circumventricular organs located within the brain allow the hypothalamus to sample the chemistry of extracellular fluid and make adjustments to organ function as necessary to maintain homeostasis.
• The hypothalamus is also the location of the master clock that entrains most organs to a circadian rhythm. The master clock resides in the suprachiasmatic nucleus, which exerts control both through direct neural connections to organs and through endocrine control. Entrainment of endocrine organs is mediated by the pineal gland and melatonin release.