BARR'S The Human Nervous System: An anatomical viewpoint, 9th Edition

PART 2 - Regional Anatomy of the Central Nervous System

Chapter 9

Reticular Formation

Important Facts

  • The reticular formation of the brain stem contains several populations of neurons with long dendrites surrounded by interlacing bundles of myelinated axons.
  • The precerebellar reticular nucleiare probably concerned with coordination of muscle contractions.
  • The raphe nucleiinclude many serotonergic neurons, with extensively distributed axons. Rostrally projecting serotonergic neurons are active in sleep. Caudally projecting neurons, which receive afferents from the periaqueductal gray matter, modulate pain sensation.
  • The central groupof nuclei includes the cells of origin of motor reticulospinal fibers. Rostral projections are concerned with eye movements and with the conscious state.
  • Cholinergic reticular nucleiinfluence stereotyped movements through connections with the central group and the basal ganglia of the forebrain. They are also active in rapid eye movement sleep. Neuronal circuitry for consciousness and sleep also involves the hypothalamus, thalamus, and cerebral cortex.
  • Catecholaminergic neuronsin the locus coeruleus and elsewhere have axons that go to most parts of the brain and spinal cord, probably to increase the speed of reflex responses and the general level of alertness.
  • Through connections with appropriate sensory, motor, and autonomic neurons, the laterally located parvocellular, parabrachial, and superficial medullary reticular areas are concerned with the regulation of feeding and of the respiratory and circulatory systems.
  • The area postrema, which contains permeable blood vessels, is a chemoreceptor that mediates some physiological responses to bloodborne stimuli, including drug-induced vomiting.
  • The paramedian pontine reticular formation, the perihypoglossal nuclei, and the accessory oculomotor nuclei are involved in the control of eye movements.

This chapter describes the anatomy and connections of the groups of neurons that constitute the reticular formation of the brain stem and reviews the involvement of the reticular formation in sleep and consciousness as well as in sensory and motor functions. The chapter also provides descriptions of a few other nuclei in the brain stem that are not discussed inChapters 7 and 8.

Broadly defined, the reticular formation consists of a substantial part of the dorsal part of the brain stem in which the groups of neurons and intersecting bundles of fibers present a netlike (reticular) appearance in transverse sections. It excludes nuclei of cranial nerves, long tracts that pass through the brain stem, and the more conspicuous masses of gray matter. Some “excluded” structures, however, such as the medial lemniscus and the nucleus ambiguus, are located within the territory of the reticular formation. The neurons of the reticular nuclei all have unusually long dendrites that extend into parts of the brain stem remote from the cell bodies. Their architecture enables them to receive and integrate synaptic inputs from most or all of the axons that project to or through the brain stem.

Through its direct and indirect connections with all levels of the central nervous system (CNS), the reticular formation contributes to several functions, including the sleep-arousal cycle, perception of pain, control of movement, and regulation of visceral activity. Although such adjectives as “primitive” and “diffuse” have been applied to the reticular formation, it is not a mass of randomly interconnected neurons.

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The parts of the reticular formation differ from one another in their cytoarchitecture, connections, and physiological functions. Aggregations of neurons are thereby recognized and are called nuclei, even though not all are as clearly circumscribed as nuclei elsewhere. As in every part of the nervous system, information obtained through research continues to reveal higher and higher degrees of orderly structural organization than were previously thought to exist.

 

FIGURE 9-1 Diagram showing the positions of the larger nuclei of the reticular formation of the brain stem.

Nuclei of the Reticular Formation

The nuclei of the reticular formation (Fig. 9-1) can be classified as follows: the precerebellar nuclei, the raphe nuclei, the central group of nuclei, the cholinergic and catecholamine cell groups, the lateral parvocellular reticular area, the parabrachial area, and the superficial medullary neurons. Additionally

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functionally designated “centers,” recognized mainly from experiments in animals, are present that do not always correspond to anatomically defined populations of neuronal cell bodies.

PRECEREBELLAR RETICULAR NUCLEI

The lateral reticular nucleus (see Figs. 9-1 and 9-2A), the paramedian reticular nucleus (see Fig. 9-2A), and the pontine reticulotegmental nucleus (see Figs. 9-1 and 9-2D) project to the cerebellum. These precerebellar reticular nuclei are functionally quite separate from the rest of the reticular formation; they are briefly considered in Chapter 10, which deals with the cerebellum.

RAPHE NUCLEI

The raphe nuclei are groups of neurons either in or adjacent to the midline (raphe) of the brain stem, interspersed among bundles of decussating axons. Raphe nuclei with different cytoarchitecture and efferent projections are recognized at different levels (see Figs. 9-1 and 9-2). Many raphe neurons synthesize and secrete serotonin (5-hydroxytryptamine), and this amine is believed to be their principal synaptic transmitter. The axons of the serotonergic raphe neurons are thin, unmyelinated, and greatly branched. They are distributed to gray matter throughout the CNS. Their most prominent projections are summarized in Figure 9-3.

The connections of the medullary raphe nuclei with the periaqueductal gray matter and the spinal dorsal horn (and trigeminal sensory nuclei) are important from a clinical standpoint because activity of this pathway can suppress the conscious awareness of pain (see Chapter 19). The pontine and mesencephalic raphe nuclei project to the cerebellum and with all parts of the cerebrum, including the cerebral cortex, basal ganglia, and limbic system.

The best understood functions of the more rostrally located raphe nuclei are those related to sleep. They are discussed later in this chapter.

CENTRAL GROUP OF RETICULAR NUCLEI

The central group includes medially located nuclei in the medulla and pons and the cuneiform and subcuneiform nuclei in the midbrain (see Figs. 9-1 and 9-2). The latter two are laterally located but are included in the central group because of their similar connections and functions. The paramedian pontine reticular formation (PPRF), which is importantly involved in conjugate lateral movements of the eyes (see Chapter 8), includes neurons in the medial parts of the two pontine reticular nuclei. The gigantocellular reticular nucleus (Fig. 9-2B) includes some serotonin neurons, which have projections similar to those of neurons in the nearby nucleus raphes magnus.

The central nuclei receive afferents from all the general and special sensory systems and from the reticular formation of the midbrain, the cholinergic reticular nuclei (see below), the hypothalamus, and the premotor area of the cerebral cortex (Fig. 9-4).

Neurons of the central reticular nuclei typically have axons with long ascending and descending branches. In the brain stem, these axons also have numerous horizontally directed collateral branches, which synapse with the long dendrites of other reticular neurons (Fig. 9-5), including those of the raphe and catecholamine nuclei. The long descending axons constitute the reticulospinal tracts, located in the ventral and lateral funiculi of the spinal white matter (see Fig. 5-10). The reticulospinal tracts are important motor pathways (discussed later in this chapter and in Chapters 5 and 23). Ascending axons from the central group of reticular nuclei travel in the central tegmental tract. The involvement of the ascending projections in maintaining consciousness is reviewed later in this chapter. The reticulothalamic projection also provides an interaction with the corpus striatum, which has motor and other functions (see Chapters 12 and 23).

CHOLINERGIC NEURONS

The rostral part of the reticular formation contains two groups of neurons that use acetylcholine as their synaptic transmitter. The larger of these is in the pedunculopontine nucleus(see Figs. 9-1, 9-2, and 9-6) in the rostral pons and caudal midbrain. The smaller lateral dorsal tegmental nucleus is nearby, extending from the pontine periventricular gray matter into the periaqueductal gray matter. These nuclei receive afferents from nearby

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noradrenergic (locus coeruleus) and serotonergic (raphe) nuclei, from histaminergic neurons in the hypothalamus and inhibitory (gamma-aminobutyrate [GABA]) descending fibers from the pallidum (see Chapter 12), and from the preoptic area. The cholinergic neurons of the reticular formation have long, branching axons, which synapse with neurons in the central group of pontine reticular nuclei and the locus coeruleus. Axons of pontine cholinergic neurons have also been traced rostrally to the substantia nigra, subthalamic nucleus, intralaminar thalamic nuclei, and basal cholinergic nuclei of the forebrain (see

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Chapter 12). Electrophysiological studies implicate cholinergic reticular nuclei in stereotyped motor functions, such as locomotion, and in consciousness and arousal.

 

FIGURE 9-2 Transverse sections of the brain stem. The left side of each figure shows nuclei and tracts that are major anatomical landmarks. The right side shows the positions of reticular and other nuclei discussed in this chapter. Black dots indicate precerebellar nuclei, red dots indicate groups of serotonin- and catecholamine-containing neurons, and blue dots indicate other nuclei.

Transverse sections of the brain stem. The left side of each figure shows nuclei and tracts that are major anatomical landmarks. The right side shows the positions of reticular and other nuclei discussed in this chapter. Black dots indicate precerebellar nuclei, red dots indicate groups of serotonin- and catecholamine-containing neurons, and blue dots indicate other nuclei. (A) Nuclei at the level of the caudal pole of the inferior olivary nucleus, in the closed part of the medulla. (The unlabeled red dots indicate scattered adrenergic neurons.) (B) Nuclei at the level of the rostral pole of the inferior olivary nucleus, in the open part of the medulla. (The unlabeled red dots indicate groups of noradrenergic and adrenergic neurons. The blue dots dorsolateral to the inferior olivary nucleus indicate the probable position of the ventral superficial reticular area of the medulla.) (C) Nuclei in the caudal pontine tegmentum, at the level of the internal genu of the facial nerve. (D) Pontine tegmentum at a level rostral to the trigeminal motor nucleus. (E) Nuclei at the level of the caudal end of the inferior colliculus.

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FIGURE 9-2 (continued)

 

FIGURE 9-3 Major connections of the serotonergic raphe nuclei.

CATECHOLAMINE NUCLEI

The catecholamines are noradrenaline (norepinephrine), adrenaline (epinephrine), and dopamine. The largest group of central noradrenergic neurons, and the only one easily seen in ordinary anatomical preparations, is the locus coeruleus or nucleus pigmentosus (see Figs. 9-2C and 9-2D), at the pontomesencephalic junction. Six smaller groups of noradrenergic neurons are present in the lateral part of the reticular formation in the medulla, pons, and midbrain. Two groups of adrenergic neurons are present in the medulla, one in the ventrolateral reticular formation and the other within the solitary nucleus (see Figs. 9-2A and 9-2B).

The afferent connections of the locus coeruleus and other noradrenergic nuclei of the human brain stem are unknown. Experimental work (mostly with nonprimate animals) suggests that the noradrenergic neurons fire spontaneously but are modulated by neurons in other parts of the reticular formation and in the hypothalamus. Noradrenergic projections are better known, even in primates, because the axons and their terminal branches are histochemically demonstrable.

Each noradrenergic neuron has an unmyelinated axon with numerous long branches. These branches go to many regions of the CNS. Most of the efferent axons of the locus coeruleus travel rostrally in the central tegmental tract and the medial forebrain bundle. Descending noradrenergic axons arise predominantly from

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the lateral medullary catecholamine nuclei. The distribution of the central noradrenergic system is summarized in Figure 9-7.

 

FIGURE 9-4 Major connections of the central group of reticular nuclei.

 

FIGURE 9-5 Neurons of the reticular formation. (A) Interaction between dendrites and collateral axonal branches of neurons with ascending (blue) and descending (red)projections. (B) A neuron whose axon divides into long ascending and descending branches.

The noradrenaline released by axons from the locus coeruleus and related cell groups probably acts mainly as a modulator of synapses between other neurons. The effects on spinal reflexes and on alertness are generally excitatory. Destructive lesions of the locus coeruleus do not cause unconsciousness.

PARVOCELLULAR RETICULAR AREA

The parvocellular reticular area is located in the medulla and pons, lateral to the central group and medial to the trigeminal nuclei (see Figs. 9-1 and 9-2). Afferent fibers come from these sensory nuclei and from the cerebral cortex. The neurons in the parvocellular reticular area send their axons to the motor nuclei of the hypoglossal, facial, and trigeminal nerves. These connections indicate involvement in reflexes concerned with feeding. An “expiratory center” identified by electrical stimulation in animals is located within the medullary parvocellular reticular area. Stimulation in this region can also cause acceleration of the heart and increased arterial blood pressure.

PARABRACHIAL AREA

Rostral to the parvocellular reticular area, the medial and lateral parabrachial nuclei are situated in the lateral part of the reticular formation of the caudal midbrain, close to the superior cerebellar peduncle. This area has many connections. Afferent fibers are from the solitary nucleus and from the cortex of the insula and adjoining parts of the parietal lobe. The axons of parabrachial neurons project rostrally to the hypothalamus, preoptic area, intralaminar thalamic

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nuclei, and amygdala. In many mammals, but not in primates, the parabrachial nuclei also form part of the sensory pathway for taste. Thus, the parabrachial area serves as a relay station in ascending pathways for visceral sensations. This region may also include the “pneumotaxic center,” which is recognized by physiologists as a region concerned with the regulation of respiratory rhythm. Dorsal pontine lesions can cause apneustic respiration, in which a pause of a few seconds takes place between full inspiration and the beginning of expiration.

 

FIGURE 9-6 Major connections of the cholinergic nuclei of the brain stem.

 

FIGURE 9-7 Major connections of the noradrenergic nuclei of the brain stem.

SUPERFICIAL MEDULLARY RETICULAR NEURONS

The ventral superficial reticular area in the medulla is another region concerned with cardiovascular and respiratory regulation. Afferents are from the spinal cord and solitary nucleus. They include fibers activated by the baroreceptors of the carotid and aortic sinuses and by the oxygen-sensitive chemoreceptors of the carotid and aortic bodies. Some of these medullary neurons respond directly to changes in the pH or carbon dioxide concentration in the nearby cerebrospinal fluid. The ventral superficial reticular area has efferent projections to the hypothalamus and to preganglionic autonomic neurons in the medulla and spinal cord. Functional connections also exist with the motor neurons that supply the muscles of respiration.

Functions of the Reticular Formation

SLEEP AND AROUSAL

Physiological Aspects of Consciousness

Consciousness, which is awareness of oneself and one's surroundings, is accompanied by neuronal activity in the whole cerebral cortex. Loss of consciousness occurs normally in sleep and abnormally with injuries or diseases that affect the brain. Profound loss of consciousness may be caused by extensive damage to the cerebral cortex or by localized destructive lesions in certain parts of the brain stem that have extensive divergent projections to the cortex. Impairment of consciousness is evaluated clinically by testing responses to sensory stimuli (see clinical note on the Glasgow coma scale).

The sleeping and awake states normally follow a rhythm with the same periodicity as the alternation of night and day. Within the nocturnal phase, sleep may be light (easily awakened) or deep (requiring a strong sensory stimulus for arousal). In addition, there are episodes of sleep in which there are rapid eye movements (REM sleep). At such times, the muscles of the trunk and limbs are relaxed, and a substantial sensory stimulus is needed for arousal, but the cerebral cortex is very active. A person suddenly awakened from REM sleep usually reports dreaming.

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The resistance to arousal in REM sleep is attributed to inhibition of transmission from the thalamus to the cerebral cortex in all the specific sensory pathways (e.g., somatic, auditory). The muscular relaxation is mediated by neurons in the reticular formation that inhibit motor neurons in the spinal cord.

Varying levels of consciousness are paralleled by changes in the electroencephalogram (EEG), which is a crude indicator of the activity of the cerebral cortex. The fluctuations in voltage recorded from a point on the scalp are the sum of the variations in the membrane potentials of the dendrites of neurons in the underlying cerebral cortex (see also Chapter 14). Dendritic potentials are responses to activity of afferent axons, most of which come from neurons in the thalamus. Whereas large potentials are recorded when groups of thalamic neurons fire synchronously, low-voltage activity indicates that each cortical neuron is responding differently to its thalamic afferents. The EEG waves of a fully alert person are of low voltage and high frequency, indicating desynchronization of thalamocortical circuits. With progressive deepening of sleep, the waves become taller (synchronization) and longer (“slow-wave sleep”). In REM sleep, the EEG is desynchronized despite the fact that such sleep is deep in the sense of being resistant to sensory stimulation. Various abnormalities—notably, reduced voltage and frequency—are seen in the EEGs of comatose patients. The absence of recordable electrical activity (flat EEG) indicates death of the cerebral cortex.

CLINICAL NOTE

The Glasgow Coma Scale

This simple quantitative assessment of impaired consciousness is made by scoring for opening of the eyes and for vocal and motor responses to stimuli of graded intensity (Table 9-1).

The maximum (fully conscious) score of 15 is recorded as E4 V5 M6. With a state of coma, a term reserved for unconsciousness with little or no response to stimuli, the total Glasgow score is 8 or below. The three components are recorded separately because it is not always possible to evaluate all of them. For example, facial injuries and swelling may prevent opening of the eyes, intubation of the trachea prevents the testing of vocal responses, and a concurrent spinal injury or multiple fractures may prevent motor responses. Meaningful scores cannot usually be obtained in children younger than age 2 years.

The Glasgow coma scale is useful because of its simplicity and because the scores correlate well with clinical outcome in cases of brain injury. Not surprisingly, deep coma is commonly associated with a poor prognosis.

TABLE 9-1 The Glasgow Coma Scale

Eye Opening (E)

Vocal Response (V)

Motor Response (M)

Spontaneous = 4

Conversation normal = 5

Normal = 6

To voice = 3

Converses but disoriented = 4

Localized response to pain = 5

To pain = 2

Says words but incoherent = 3

Withdrawal from pain (flexion) = 4

Absent = 1

Makes incomprehensible sounds = 2

Rigidity with limb flexion (“decorticate posture”) = 3

 

Absent = 1

Rigidity with limb extension (“decerebrate posture”) = 2

   

Absent = 1

   

Total = E + V + M

Neuroanatomical Correlates of Consciousness and Sleep

The generalized activity of the cerebral cortex that constitutes an alert or wakeful condition occurs only when there is adequate cortical

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excitation by neurons whose cell bodies are in the brain stem and thalamus. The ascending pathways that stimulate the whole cortex are anatomically separate from the specific sensory systems (see Chapters 17 and 19, 20, 21, and 22) and from the corticopetal projections of the cerebellum (see Chapter 10) and basal ganglia (see Chapters 12 and 23). Irreversible coma follows bilateral destruction of the medial parts of the brain stem at or above the upper pontine levels. Transmission in the more laterally located sensory pathways is not interrupted by medially located lesions that cause coma. The integrity of the rostral pontine reticular formation and of the central tegmental tract is essential for maintaining the conscious state. At the level of the midbrain and rostral pons, the central tegmental tract contains three populations of axons from the reticular formation that directly or indirectly stimulate the whole cerebral cortex:

  1. Noradrenergic neurons(see Fig. 9-7) provide an ascending projection that excites neurons throughout the cerebral cortex. The cells of the locus coeruleus are most active in awake, attentive animals; they are less active in non-REM sleep and inactive in REM sleep.
  2. Cholinergic neuronsof the pedunculopontine nucleus (see Fig. 9-6) project to the hypothalamus, basal cholinergic nuclei of the forebrain (see later), and intralaminar thalamic nuclei, which, in their turn, have extensive although sparse projections to all parts of the cerebral cortex. These neurons are active in the awake state and in REM sleep but are quiescent in non-REM sleep.
  3. The central group of reticular nuclei(especially the oral pontine reticular nucleus) sends axons to the intralaminar nuclei of the thalamus and to the basal cholinergic nuclei of the forebrain (see later). The central reticular neurons are a mixed population, differently active in all states of consciousness.

Groups of neurons in the diencephalon and telencephalon stimulate the cerebral cortex in a general way. The intralaminar thalamic nuclei (see Chapter 11) provide an essential link in most of the ascending pathways concerned with both arousal and REM sleep (Fig. 9-8). In addition to the connections already mentioned, the intralaminar nuclei receive collateral branches from all the sensory tracts that go to other nuclei of the thalamus. Sensory stimuli that cause arousal from sleep may do so by way of these branches. Lesions that bilaterally damage the intralaminar nuclei cause coma. The posterior part of the hypothalamus (see Chapter 11) contains the tuberomamillary nucleus, which is composed of histamine-secreting neurons with axons that branch profusely in the thalamus and also extend to many parts of the CNS, including the cerebral cortex. Pharmacological studies indicate that histamine of neuronal origin participates in arousal. The sedative side effects of traditional antihistaminic drugs (H1-receptor blockers) are probably caused by competitive inhibition of the action of histamine on cortical neurons. The basal cholinergic nuclei of the forebrain (see Chapter 12) also stimulate neurons throughout the cerebral cortex.

Deep (non-REM) sleep is associated with diminished activity of the systems just described. In addition, some neurons in the brain stem and hypothalamus actively promote sleep:

  1. The serotonergic raphe neuronshave axons that go to all parts of the CNS. The raphe neurons are active in deep sleep, which may be caused partly by a widespread inhibitory action of serotonin in the thalamus and cerebral cortex. Serotonergic neurons are less active in REM sleep, which may be caused partly by occasional release of the telencephalic neurons from serotonergic inhibition. A simultaneous reduction of inhibition of the caudal pontine reticular nucleus (the PPRF) may account for the accompanying movements of the eyes.
  2. In the lateral hypothalamus, some neurons produce a pair of peptides, orexin-A and orexin-B, which are active in the awake state. The orexinsare also called hypocretins-1 and -2. The long axons of orexin neurons extend to most parts of the brain. One of their actions is stimulation of the cholinergic neurons of the pedunculopontine nucleus. Deficiency of orexin in dogs, mice, and humans is associated with narcolepsy, a condition in which the waking state is frequently

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interrupted by brief episodes of REM sleep.

 

FIGURE 9-8 The ascending reticular-activating system. This diagram shows the groups of neurons that are more active in the alert state and less active during slow-wave (non-REM) sleep. With the notable exception of the locus coeruleus, these neurons are active also in REM sleep.

  1. The suprachiasmatic nucleusof the hypothalamus (see Chapter 11) contains neurons whose patterns of firing follow a 24-hour cycle, serving as an internal clock for the brain. Axons from the suprachiasmatic nucleus contact the orexin neurons of the lateral hypothalamus and the dorsomedial hypothalamic nucleus

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(see Fig. 11-14), which projects caudally to the locus coeruleus. These connections provide circuitry that may facilitate sleeping during the night rather than during the day.

  1. The cholinergic neuronsof the pedunculopontine and lateral dorsal tegmental nuclei are as active in REM sleep as they are in the awake state.
  2. In the preoptic area, immediately anterior to the hypothalamus, a population of GABA-ergic neurons contains a peptide, galanin. These inhibitory neurons are active in deep (non-REM) sleep. Their axons go to the tuberomamillary nucleus, the locus coeruleus, and the cholinergic reticular nuclei. Destructive lesions in the preoptic area cause insomnia, indicating that this region is essential for the occurrence of sleep.

In REM sleep, suppression of transmission in specific sensory pathways takes place, accounting for the high threshold for arousal by sensory stimuli. This is believed to be mediated by rostrally projecting cholinergic neurons (Fig. 9-9) that stimulate the reticular nucleus of the thalamus (see also Chapter 11). This nucleus contains GABA-ergic neurons that inhibit transmission from the other thalamic nuclei to the cerebral cortex. The relaxation of limb muscles in REM sleep is mediated by reticulospinal fibers, some of which use glycine as an inhibitory transmitter.

PAIN

Through spinal afferents and projections to the thalamus, the central group of reticular nuclei forms part of an ascending pathway for the poorly localized perception of pain. Such sensation persists after transection of the spinothalamic tracts (see Chapter 19).

descending inhibitory pathway consists of the axons of serotonergic raphe neurons that project to the dorsal horn and spinal trigeminal nucleus. This system inhibits the rostral transmission of action potentials that report pain. Electrical stimulation of the periaqueductal gray matter (which projects to the raphe nuclei in the medulla) results in loss of the ability to experience pain from sites of injury or disease. This descending pathway is discussed in Chapter 19.

SOMATIC MOTOR FUNCTIONS

The reticulospinal tracts constitute one of the major descending pathways involved in the control of movement; the others are the corticospinal and vestibulospinal tracts. Equivalent reticulobulbar connections supply the motor nuclei of the cranial nerves. Animal experiments indicate that many reticulospinal fibers are the axons of cells in the caudal and oral pontine reticular nuclei and the gigantocellular nucleus of the medulla. Most of these fibers descend to the spinal cord without crossing the midline. Some end ipsilaterally in the ventral horn, and others decussate before terminating. The reticulospinal tracts, consequently, project both ipsilaterally and bilaterally to the spinal gray matter. They end on interneurons and influence the motor neurons indirectly through synaptic relays within the spinal cord.

With respect to motor functions, important afferents to the central group of reticular nuclei come from the motor cortex of the cerebral hemispheres, the cholinergic pedunculopontine nucleus (see Figs. 9-2D and 9-6), the cerebellar nuclei, and the spinal cord.

The raphespinal tract is a reticulospinal pathway best known for the involvement of its serotonergic neurons in the modulation of pain sensation. Raphespinal projections may also modulate the activities of motor neurons, which are made more excitable by serotonin. Drugs that block the action of serotonin have been used clinically to alleviate the spasticity that follows damage to the major descending motor pathways.

VISCERAL ACTIVITIES

Certain regions in the reticular formation regulate visceral functions and breathing through connections rostrally with the amygdala and hypothalamus and caudally with nuclei of the autonomic outflow and with respiratory motor neurons in the phrenic nucleus and thoracic cord. The functions of the superficial medullary reticular neurons in mediating reflex responses to the systemic blood pressure and the degree of oxygenation of the

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blood were mentioned earlier in this chapter. Other cardiovascular and respiratory regions, commonly referred to as “centers,” have been identified by electrical stimulation within the brain stem in laboratory animals. Some of these centers are fields within the network of dendrites in the reticular formation rather than compact collections of cell bodies. Maximal inspiratory and expiratory responses are obtained from the gigantocellular nucleus and the parvocellular reticular area, respectively, in the medulla, and respiratory rhythm is controlled by the pneumotaxic center in the parabrachial area.

 

FIGURE 9-9 Diagram showing groups of neurons that are active in sleep. The serotonergic neurons and the GABA-ergic hypothalamic neurons are more active in slow-wave (non-REM) sleep. The other pathways are active in REM sleep though the physiological role of the orexin neurons is still uncertain. The arrows pointing up indicate extensive distribution of axonal branches to the cortex. The descending pathways mediate the inhibition of motor activity during periods of REM sleep.

Stimulation in the medial part of the reticular formation of the medulla has a depressor effect on the circulatory system, with slowing of the heart rate and lowering of blood pressure. The opposite effects are produced by stimulation in laterally located sites. Damage to the brain stem is life threatening because of the presence of these regions involved in the control of vital functions.

Miscellaneous Nuclei of the Brain Stem

The area postrema is a narrow strip of neural tissue in the caudal part of the floor of the fourth ventricle near the obex (see Fig. 6-3). The blood-brain barrier, which elsewhere prevents certain substances from entering nervous tissue from the blood, is lacking here. Among other connections, the area postrema has reciprocal connections with the solitary nucleus. The area has been shown experimentally to be a chemoreceptor region for emetic drugs such as apomorphine and digoxin. It may, therefore, function in the physiology of vomiting.

The perihypoglossal nuclei are three quite conspicuous groups of neurons in the caudal medulla: the nucleus intercalatus (see Fig. 9-2A), the nucleus of Roller (ventrolateral to the hypoglossal nucleus), and the nucleus prepositus hypoglossi (see Fig. 9-2B). The nucleus prepositus hypoglossi is the largest of the three, and it is continuous at its rostral end with the PPRF (see Fig. 8-5).

These nuclei receive afferents from several sources, including the cerebral cortex, vestibular nuclei, accessory oculomotor nuclei, and PPRF. Efferent fibers proceed mainly to the nuclei of cranial nerves III, IV, and VI, which they reach by passing into the medial longitudinal fasciculus. The perihypoglossal nuclei form part of the complex circuitry for movements of the eyes. Lesions in the nucleus prepositus hypoglossi impair the ability to keep the eyes fixed on a visual target, although conjugate movements are still performed accurately.

The accessory oculomotor nuclei are the interstitial nucleus of Cajal, nucleus of Darkschewitsch, nucleus of the posterior commissure, and rostral interstitial nucleus of the medial longitudinal fasciculus. They are situated at the junction of the midbrain and the diencephalon (Fig. 9-10) and are concerned with movements of the eyes in the vertical plane (seeChapter 8).

The periaqueductal gray matter surrounds the cerebral aqueduct of the midbrain. In laboratory animals, afferent and efferent connections have been traced with regions ranging from the spinal cord to parts of the telencephalon, but the periaqueductal gray matter's physiological role is largely obscure. As mentioned earlier, electrical stimulation of the periaqueductal gray matter causes analgesia, and this effect is mediated by way of the descending projection of the nucleus raphes magnus in the medulla. The nucleus of Darkschewitsch is located within the territory of the periaqueductal gray matter, but it is generally considered to be one of the accessory oculomotor nuclei.

The interpeduncular nucleus is located in the midline, ventral to the periaqueductal gray matter and near the roof of the most rostral part of the interpeduncular fossa. This nucleus lies on a pathway through which the limbic system projects to autonomic nuclei in the brain stem and spinal cord. Lateral to the interpeduncular nucleus, in the medial part of the cerebral peduncle, is a population of dopamine-secreting neurons known as the ventral tegmental area. This, too, has connections with the limbic system and is discussed in Chapter 18.

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FIGURE 9-10 Some nuclei at the junction of the midbrain and diencephalon, at the level between those of Figures 7-15 and 11-7. The accessory oculometer nuclei are shown in red and the parasympathetic Edinger-Westphal nucleus in green. Parts of the thalamus (light blue) are included in the section, and some major tracts of fibers are colored yellow.

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Crabtree JW. Intrathalamic sensory connections mediated by the thalamic reticular nucleus. Cell Mol Life Sci 1999;56: 683-700.

Ferguson AV. The area postrema: a cardiovascular control centre at the blood-brain interface? Can J Physiol Pharmacol 1991;69:1026-1034.

Huang XF, Paxinos G. Human intermediate reticular zone: a cyto- and chemoarchitectonic study. J Comp Neurol 1995;360:571-588.

Inglis WL, Winn P. The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation. Prog Neurobiol 1995;47:1-29.

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