Cranial nerve nuclei are organized in rostrocaudal columns that are homologous to the sensory and motor laminae of the spinal cord (see Chapters 22 and 34). This pattern is best understood from the developmental plan of the caudal neural tube that gives rise to the brain stem and spinal cord.
The transverse axis of the embryonic caudal neural tube is subdivided into alar (dorsal) and basal (ventral) plates by the sulcus limitans, a longitudinal groove along the lateral walls of the central canal, fourth ventricle, and cerebral aqueduct (Figure 45–4). The alar plate forms the sensory components of the dorsal horn of the spinal cord, whereas the basal plate forms the motor components of the ventral horn. The intermediate gray matter is made up primarily of the interneurons that coordinate spinal reflexes and motor responses.
The developmental plan of the brain stem is the same general plan as that of the spinal cord.
A. The neural tube is divided into a dorsal sensory portion (the alar plate) and a ventral motor portion (the basal plate) by a longitudinal groove, the sulcus limitans.
B–D. During development the sensory and motor cell groups migrate into their adult positions, but largely retain their relative locations. In maturity (D) the sulcus limitans (dashed line) is still recognizable in the walls of the fourth ventricle and the cerebral aqueduct, demarcating the border between dorsal sensory structures (orange) and ventral motor structures (green). The section in D is from the rostral medulla.
The brain stem shares this basic plan. As the central canal of the spinal cord opens into the fourth ventricle, the walls of the neural tube are splayed outward so that the dorsal sensory structures (derived from the alar plate) are displaced laterally whereas the ventral motor structures (derived from the basal plate) remain more medial. The nuclei of the brain stem are divided into general nuclei, which serve functions similar to those of the spinal cord laminae, and special nuclei, which serve functions unique to the head (such as hearing, balance, taste, and control of the branchial musculature).
Adult Cranial Nerve Nuclei Have a Columnar Organization
Overall, the brain stem nuclei on each side are organized in six rostrocaudal columns, three of sensory nuclei and three of motor nuclei (Figure 45–5). These are considered below, in dorsolateral to ventromedial sequence. The columns are discontinuous—the nuclei are not packed solidly along the rostrocaudal axis of the brain stem. Nuclei with similar functions (sensory or motor, somatic or visceral) have similar dorsolateral-ventromedial positions at each level of the brain stem.
Adult cranial nerve nuclei are organized in six functional columns on the rostrocaudal axis of the brain stem.
A. This dorsal view of the human brain stem shows the location of the cranial nerve sensory nuclei (right) and motor nuclei (left).
B. A schematic view of the functional organization of the motor and sensory columns.
C. The medial-lateral arrangement of the cranial nerve nuclei is shown in a cross section at the level of the medulla (compare with Figure 45–4).
Within each motor nucleus, motor neurons for an individual muscle are also arranged in a cigar-shaped longitudinal column. Thus each motor nucleus in cross section forms a mosaic map of the territory that is innervated. For example, in a cross section through the facial nucleus the clusters of neurons that innervate the different facial muscles form a topographic map of the face.
General Somatic Sensory Column
The general somatic sensory column occupies the most lateral region of the alar plate and includes the trigeminal sensory nuclei (N. V). The spinal trigeminal nucleus is a continuation of the dorsal-most laminae of the spinal dorsal horn (Figure 45–5A) and is sometimes called the medullary dorsal horn. Its outer surface is covered by the spinal trigeminal tract, a direct continuation of Lissauer's tract of the spinal cord (see Chapter 24), thus allowing some cervical sensory fibers to reach the trigeminal nuclei and some trigeminal sensory axons to reach the dorsal horn in upper cervical segments. This arrangement allows dorsal horn sensory neurons to have a range of inputs that are much broader than that of individual spinal or trigeminal segments, and ensures the integration of trigeminal and upper cervical sensory maps.
The spinal trigeminal nucleus receives sensory axons from the trigeminal ganglion (N. V) and from all cranial nerve sensory ganglia concerned with pain and temperature in the head, including geniculate ganglion (N. VII) neurons that relay information from the external auditory meatus, petrosal ganglion (N. IX) cells that convey information from the posterior part of the palate and tonsillar fossa, and nodose ganglion (N. X) axons that relay information from the posterior wall of the pharynx. The spinal trigeminal nucleus thus represents the entire oral cavity as well as the surface of the face.
The somatotopic organization of the afferent fibers is inverted: The forehead is represented ventrally and the oral region dorsally. Axons from the spinal trigeminal nucleus descend on the same side of the brain stem into the upper spinal cord, where they cross the midline in the anterior commissure with spinothalamic axons and join the opposite spinothalamic tract. (For this reason, upper cervical spinal cord injury may cause facial numbness.) The trigeminothalamic axons then ascend back through the brain stem, providing inputs to brain stem nuclei for reflex motor and autonomic responses in addition to carrying pain and temperature information to the thalamus.
The principal sensory trigeminal nucleus lies in the mid pons just lateral to the trigeminal motor nucleus. It receives the axons of neurons in the trigeminal ganglion concerned with position sense and fine touch discrimination, the same types of sensory information carried from the rest of the body by the dorsal columns. The axons from this nucleus are bundled with those from the dorsal column nuclei in the medial lemniscus, through which they ascend to the ventroposterior medial thalamus.
An additional component of the trigeminal sensory system, located at the midbrain level in the lateral surface of the periaqueductal gray matter, is the mesencephalic trigeminal nucleus, which relays mechanosensory information from the muscles of mastication and the periodontal ligaments. The large cells of this nucleus are not central neurons but primary sensory ganglion cells that derive from the neural crest and, unlike their relatives in the trigeminal ganglion, migrate into the brain during development. The central branches of the axons of these pseudo-unipolar cells contact motor neurons in the trigeminal motor nucleus, providing monosynaptic feedback to the jaw musculature, critical for the precise control of chewing movements.
Special Somatic Sensory Column
The special somatic sensory column has inputs from the acoustic and vestibular nerves and develops from the intermediate region of the alar plate. The cochlear nuclei (N. VIII), which lie at the lateral margin of the brain stem at the pontomedullary junction, receive auditory afferents from the spiral ganglion of the cochlea. The output of these nuclei is relayed through the pons to the superior olivary and trapezoid nuclei and bilaterally on to the inferior colliculus (see Chapter 31). The vestibular nuclei (N. VIII) are more complex. They include four distinct cell groups that relay information from the vestibular ganglion to various motor sites in the brain stem, cerebellum, and spinal cord concerned with maintaining balance and coordination of eye and head movements (see Chapter 40).
The visceral sensory column is concerned with special visceral information (taste) and general visceral information from the facial (VII), glossopharyngeal (IX), and vagus nerves (X). It is derived from the most medial tier of neurons in the alar plate. All of the afferent axons terminate in the nucleus of the solitary tract. The solitary tract is analogous to the spinal trigeminal tract or Lissauer's tract, bundling afferents from different cranial nerves as they course rostrocaudally along the length of the nucleus. As a result, visceral sensory information from different afferent nerves produces a unified visceral sensory map of the body in the nucleus.
Special visceral afferents carrying taste information from the anterior two-thirds of the tongue reach the nucleus of the solitary tract through the chorda tympani branch of the facial nerve, whereas those from the posterior parts of the tongue and oral cavity arrive through the glossopharyngeal and vagus nerves. These afferents terminate in roughly somatotopic fashion in the anterior third of the nucleus of the solitary tract. General visceral afferents are relayed through the glossopharyngeal and vagus nerves. Those from the rest of the gastrointestinal tract (down to the transverse colon) terminate in the middle portion of the solitary nucleus in topographic order, whereas those from the cardiovascular and respiratory systems terminate in the caudal and lateral portions.
The solitary nucleus projects directly to parasympathetic and sympathetic preganglionic motor neurons in the medulla and spinal cord that mediate various autonomic reflexes, as well as to parts of the reticular formation that coordinate autonomic and respiratory responses. Most ascending projections from the viscera to the forebrain are relayed through the parabrachial nucleus in the pons, although some reach the forebrain directly from the solitary nucleus. Together the solitary and parabrachial nuclei supply visceral sensory information to the hypothalamus, basal forebrain, amygdala, thalamus, and cerebral cortex.
General Visceral Motor Column
All motor neurons initially develop adjacent to the floor plate, a longitudinal strip of non-neuronal cells at the ventral midline of the neural tube (see Chapter 52). Neurons fated to become the three types of brain stem motor neurons migrate dorsolaterally, settling in three distinct rostrocaudal columns. The neurons that form the general visceral motor column migrate to the most lateral region of the basal plate, just medial to the sulcus limitans.
The Edinger-Westphal nucleus (N. III) lies next to the oculomotor complex just below the floor of the cerebral aqueduct. It contains preganglionic neurons that control pupillary constriction and lens accommodation through the ciliary ganglion.
The superior salivatory nucleus (N. VII) lies just dorsal to the facial motor nucleus and comprises parasympathetic preganglionic neurons that innervate the sublingual and submandibular salivary glands and the lacrimal glands and intracranial circulation through the sphenopalatine and submandibular parasympathetic ganglia.
Parasympathetic preganglionic neurons associated with the gastrointestinal tract form a column at the level of the medulla just dorsal to the hypoglossal nucleus and ventral to the nucleus of the solitary tract. At the most rostral end of this column is the inferior salivatory nucleus (N. IX) comprising the preganglionic neurons that innervate the parotid gland through the otic ganglion. The rest of this column constitutes the dorsal motor vagal nucleus (N. X). Most of the preganglionic neurons in this nucleus innervate the gastrointestinal tract below the diaphragm; a few are cardiomotor neurons.
The nucleus ambiguus (N. X) is a cluster of neurons that runs the rostrocaudal length of the ventrolateral medulla and contains parasympathetic preganglionic neurons that innervate thoracic organs, including the esophagus, heart, and respiratory system, as well as special visceral motor neurons that innervate the striated muscle of the larynx and pharynx, and neurons that generate respiratory motor patterns (see below). The parasympathetic preganglionic neurons are organized in topographic fashion, with the esophagus represented most rostrally and dorsally.
Special Visceral Motor Column
The special visceral motor column includes motor nuclei that innervate muscles derived from the branchial (pharyngeal) arches. Because these arches are homologous to the gills in fish, the muscles are considered special visceral muscles, even though they are striated in mammals. During development these cell groups migrate to an intermediate position in the basal plate and are eventually located ventrolaterally in the tegmentum. The trigeminal motor nucleus (N. V) lies at midpontine levels and innervates the muscles of mastication. Associated with it are the accessory trigeminal nuclei that innervate the tensor tympani, tensor veli palatini, and mylohyoid muscles, and the anterior belly of the digastric muscle.
The facial motor nucleus (N. VII) lies caudal to the trigeminal motor nucleus at the level of the caudal pons and innervates the muscles of facial expression. During development facial motor neurons migrate medially and rostrally around the medial margin of the abducens nucleus before turning laterally, ventrally, and caudally toward their definitive location at the pontomedullary junction (Figure 45–6A). This sinuous course of the axons forms the internal genu of the facial nerve. The adjacent accessory facial motor nuclei innervate the stylohyoid and stapedius muscles and the posterior belly of the digastric muscle.
Embryonic cranial nerve nuclei are organized segmentally.
A. In the developing hindbrain (seen here from the ventral side) special and general visceral motor neurons form in each hindbrain segment (rhombomere) except rhombomere 1 (r1). Each special visceral motor nucleus comprises neurons in two rhombomeres: the trigeminal nucleus is formed by neurons in r2 and r3, the facial nucleus by neurons in r4 and r5, the glossopharyngeal nucleus by neurons in r6 and r7, and the motor nuclei of the vagus by neurons in r7 and r8. Axons of neurons in each of these nuclei course laterally within the brain, leaving the brain through exit points in the lateral neuroepithelium (of r2, r4, r6, and r7) and running together outside the brain to form the respective cranial motor nerves (V, VII, IX, X). The trigeminal (V) nerve innervates muscles in the 1st branchial arch, the facial (VII) nerve innervates muscles in the 2nd branchial arch, and the glossopharyngeal (IX) nerve innervates muscles in the 3rd branchial arch.
All of the visceral motor neurons (green) develop initially next to the floor plate at the ventral midline; after extending their axons toward their respective exit points, the cell bodies then migrate laterally (arrows). Exceptions are the facial motor neurons formed in r4 (red); the cell bodies, after extending their axons toward the exit point, migrate caudally to the axial level of r6 before migrating laterally.
General somatic motor neurons (blue) are formed in r1 (trochlear nucleus), r5 and r6 (abducens nucleus), and r8 (hypoglossal nucleus). The cell bodies of these neurons remain close to their place of birth, next to the floor plate. The axons of abducens and hypoglossal neurons exit the brain directly, without coursing laterally. The axons of trochlear neurons (light blue) extend laterally and dorsally within the brain until, caudal to the inferior colliculus, they turn medially, decussate, and exit near the midline of the opposite side.
B. The brain stem of a mouse embryo in which fluorescent dyes label cranial nerve VII motor neurons. A red-fluorescing dye fills the cell bodies of facial motor neurons via retrograde transport from the motor root of the facial nerve. These neurons develop initially in r4 and then migrate posteriorly, alongside the floor plate, to r6 (see red neurons in part A). A green-fluorescing dye fills the cell bodies of general visceral motor neurons in r5 (see light green neurons in part A) via retrograde transport from the root of the intermediate nerve (sensory and preganglionic general visceral motor axons). (Micrograph reproduced, with permission, from Dr. Ian McKay.)
The nucleus ambiguus contains branchial motor neurons with axons that run in the glossopharyngeal and vagus nerves. These neurons innervate the striated muscles of the larynx and pharynx. During development these motor neurons migrate into the ventrolateral medulla, and as a consequence their axons form a hairpin loop within the medulla, similar to those of the facial motor axons.
General Somatic Motor Column
The neurons of the somatic motor column migrate the least during development, remaining close to the ventral midline. The oculomotor nucleus (N. III) lies at the midbrain level; it consists of five rostrocaudal columns of motor neurons innervating the medial, superior, and inferior rectus muscles, the inferior oblique muscle, and the levator of the eyelids. The motor neurons for the medial and inferior rectus and inferior oblique muscles are on the same side of the brain stem as the nerve exits, whereas those for the superior rectus are on the opposite side. The levator motor neurons are bilateral.
The trochlear nucleus (N. IV), which innervates the trochlear muscle, lies at the midbrain/rostral pontine level also on the opposite side of the brain stem from which the nerve exits. The abducens nucleus (N. VI), which innervates the lateral rectus muscle, is located at the midpontine level. The hypoglossal nucleus (N. XII) at the caudal end of the medulla consists of several columns of neurons, each of which innervates a single muscle of the tongue.
Embryonic Cranial Nerve Nuclei Have a Segmental Organization
Although the sensory and motor nuclei in the adult hindbrain are organized rostrocaudally, the arrangement of neurons at each level derives from a strikingly segmental pattern in the early embryo. Before neurons appear, the future hindbrain region of the neural plate becomes subdivided into a series of eight segments of approximately equal size, known as rhombomeres (Figure 45–6A).
Each rhombomere develops a similar set of differentiated neurons, as if the hindbrain is made up of series of modules. The even-numbered rhombomeres differentiate ahead of the odd-numbered ones. This is most clearly seen in the branchial (special visceral) motor neurons, which are readily identified early in development. Rhombomeres 2, 4, and 6 form the branchial motor nuclei of the trigeminal, facial, and glossopharyngeal nerves, respectively. Later, rhombomeres 3, 5, and 7 contribute motor neurons to these nuclei; in each case the axons of individual motor neurons extend rostrally as they join those of their even-numbered neighbor. At this developmental stage each of these nuclei is composed of homologous neurons derived from two adjacent segments. This early transverse segmental organization changes as rhombomere boundaries disappear and the dorsolateral migration of the cell bodies aligns the cells into rostrocaudal columns. The migration of the facial motor neurons of rhombomere 4 around the abducens nucleus (Figure 45–6A) generates the internal genu of the facial nerve.
The combination of the neurons of two rhombomeres into a single cranial nerve nucleus also corresponds to the relationship of the rhombomeres with the branchial arch muscles that are the targets of these motor neurons. For example, rhombomeres 2 and 3 (trigeminal) register with branchial arch 1 (mandibular), which forms the muscles of mastication; rhombomeres 4 and 5 (facial) register with branchial arch 2 (hyoid), which forms the muscles of facial expression (Figure 45–6A). Furthermore, neural crest cells from each rhombomere migrate into the corresponding branchial arches where they provide positional cues that determine the development and identity of the arch muscles.
The Organization of the Brain Stem and Spinal Cord Differs in Three Important Ways
One major difference between the organization of the brain stem and that of the spinal cord is that the long ascending and descending sensory tracts that run along the outside of the spinal cord are incorporated within the interior of the brain stem. Thus the ascending sensory tracts (the medial lemniscus and spinothalamic tract) run through the reticular formation of the brain stem as do the auditory, vestibular, and visceral sensory pathways.
A second major difference is that, in the brain stem, the cerebellum and its associated pathways form additional structures that are superimposed on the basic plan of the spinal cord. Fibers of the cerebellar tracts and nuclei are bundled with those of the pyramidal and extrapyramidal motor systems to form a large ventral portion of the brain stem. Thus, from the midbrain to the medulla the brain stem is divided into a dorsal portion, the tegmentum, which follows the basic segmental plan of the spinal cord, and a ventral portion, which contains the structures associated with the cerebellum and the descending motor pathways. At the level of the midbrain the ventral (motor) portion includes the cerebral peduncles, substantia nigra, and red nuclei. The base of the pons includes the pontine nuclei, corticospinal tract, and middle cerebellar peduncle. In the medulla the ventral motor structures include the pyramidal tracts and inferior olivary nuclei.
A third major difference is that, although the hindbrain is segmented into rhombomeres during development, there is no clear repeating pattern in the adult brain. In contrast, the spinal cord is not segmented during development but the final pattern consists of repeating segments. The prominent ladder-like arrays of ventral root axons and dorsal root ganglia suggest that segmentation is imposed by a polarizing effect of the adjacent somites into which they migrate—in each somite the rostral part attracts axonal growth cones and neural crest cells, whereas the caudal part is repulsive (see Figure 52–1). In the head such patterning is lacking as the cranial mesoderm is not segmented into somites but rather develops under the influence of the rhombomeres.