1.1 General Architecture
1.4.7 Nuclear Regions of the Mesencephalon
1.4.7.1 Overview
The nucleus of the posterior commissure is closely associ- ated with the fibers of the posterior commissure in the medial pole of the mesencephalon. It can be divided into at least five different subgroups. One subgroup, the subcommissural nucleus, contains virtually no neurons and comprises the
Gracile nucleus Dorsal motor vagal nucleus
Cuneate nucleus External cuneate nucleus Solitary tract Central sympathetic
pathway
Nucleus ambiguus Commissural nucleus
Medial longitudinal fasciculus
Medial lemniscus
Pyramidal tract Hypoglossal nerve nucleus
Spinothalamic tract Tectospinal tract
Nucleus raphe obscurus Hypoglossal nucleus Solitary tract Dorsal motor vagal nucleus
Inferior cerebellar peduncle Central sympathetic pathway
Rubrospinal tract Spinothalamic tract Nucleus ambiguus Hypoglossal nerve Prepositus nucleus
Vestibular nuclei
Medial longitudinal fasciculus Tectospinal tract Inferior olivary nucleus Medial lemniscus Pyramidal tract
d
Spinal trigeminal nucleus
e Spinal tract nucleus of the trigeminal nerve Fig. 1.14 (continued)
24 1 Neuroanatomy of the Brainstem
Medial vestibular nucleus Solitary nucleus
XII
Dorsomedial respiratory complex
Nucleus ambiguus
Ventrolateral respiratory complex
Dorsomedial respiratory complex
Ventrolateral respiratory complex
Rostral respiratory complex
Pre-Bötzinger complex Bötzinger complex Parabrachial nuclei (“pneumotaxic center”)
Diaphragm motoneurons
C3-C7 Caudal respiratory
complex
b a
Fig. 1.15 Representation of premotor brainstem respiratory areas involved in the regulation of respiratory activity. (a) The crosses within the ventrolateral respiratory complex represent the excitatory premotor neurons of the sympathetic system in the rostral ventrolateral medulla for the baroreceptor-vasomotor reflex. The dotted line in the dorsal
view of b marks the plane of section for a. (b) The parabrachial nuclei form a pneumotaxic center and modulate the dorsomedial and ventro- lateral premotor respiratory complex in the rostral medulla, which in turn activate the motoneurons of the respiratory muscles in the nucleus ambiguus. XII hypoglossal nerve nucleus
circumventricular subcommissural organ, a neurohumoral region (McKinley et al. 2004). In neurohumoral regions hormones are produced in the neurons and released into the bloodstream. Lesions in the posterior commissural nucleus or the posterior commissure are frequently caused by tumours of the nearby pineal body and can lead to vertical upward gaze paresis (Leigh and Zee 2006; Horn 2006). In primates premotor neurons for vertical and torsional sacca- des are located in the rostral interstitial nucleus of the medial longitudinal fasciculus as well as in the interstitial nucleus of Cajal (Fig. 1.14a and p. 18-22), and in the fibers of the medial longitudinal fasciculus at the anterior end of the mesencephalon.
The nucleus of Darkschewitsch is situated immediately above the interstitial nucleus of Cajal (INC) in the periaq- ueductal gray. Both the INC and the red nucleus receive and project to the inferior olive. Contrary to various older descriptions, the nucleus of Darkschewitsch does not consti- tute part of the premotor pathways for eye movements (Büttner-Ennever 2006). The area medial to the substantia nigra is named the ventral tegmental area; like the adja- cent pigmented parabrachial nucleus it contains dopamin- ergic neurons and possesses strong connections to the limbic structures (Fig. 1.14a; Holstege et al. 2004).
1.4.7.2 Pretectum
The pretectum is located just rostral to the superior colliculus below the brachium of the superior colliculus, where it forms the transition region between the brainstem and the diencephalon (Fig. 1.3). It contains several small nuclei (Borostyankoi-
Baldauf and Herczeg 2002); a number of them have special- ized visual motor functions, while others are involved, e.g. in the processing of pain stimuli (Gamlin 2006).
• Pretectal olivary nucleus: this nucleus has an important role in the mediation of the pupillary light reflex.
• Nucleus of the optic tract: it corresponds to the region which was formerly also described as the lentiform nucleus.
In primates, the pretectal olivary nucleus is completely enveloped by cells of the nucleus of the optic tract, which suggests increasing cooperation between these nuclei. The nuclei of the optic tract on both sides are connected by commissural fibers via the posterior commissure. They have an important function in the generation of optoki- netic nystagmus, smooth pursuit eye movements, and gain adaptation of the horizontal vestibuloocular reflex (Fig. 1.11 and p. 19).
• Posterior pretectal nucleus: the nucleus has tradition- ally been described as the sublentiform nucleus.
• Medial pretectal nucleus: this nucleus corresponds to the pretectal area involved in accommodation.
• Anterior pretectal nucleus: the findings of recent stud- ies provide evidence that this nucleus has an inhibitory influence on afferent pathways in the dorsal horn of the spinal cord.
1.4.7.3 Superior and Inferior Colliculi
The superior colliculus acts as a central relay station for fast orientation movements, which are also described as the ‘visual grasp reflex’. Histologically it consists of several layers
1.4 Internal Architecture 25
(I–VII). The superficial layers (I–III) receive exclusively sen- sory input from the retina and the visual cortex, while the intermediate (IV) and deep (V–VII) layers receive multimodal input from the trigeminal, auditory, somatosensory and ves- tibular systems (May 2006). The superior colliculus has an important function in the transformation of visual and audi- tory stimuli to motor signals. Electrical stimulation of the superior colliculus is followed by a saccade to the contralateral side, whose amplitude and direction depends upon the site of stimulation. The topographic representation of the visual field in the superficial layers correlates with motor map contained in the deeper layers. In the caudal superior colliculus larger sac- cades are induced by electrical stimulation and are frequently combined with movements of the head; small saccades are induced by electrical stimulation in the rostral aspect.
Stimulation in the rostral area of foveal representation leads to fixation of the eyes (Fig. 1.11 and p. 18).
The deeper layers also receive input from the cerebral cortex (frontal eye fields), the basal ganglia, including the substantia nigra (reticular part), cerebellar nuclei and the prepositus nucleus. The descending efferents of the deeper layers cross in the dorsal tegmental decussation (Meynert);
at this level it gives rise to a bundle ascending to the thala- mus, the basal ganglia, and the rostral interstitial nucleus of the medial longitudinal fasciculus, while another branch travels just below the medial longitudinal fasciculus in the tectoreticulospinal tract (predorsal bundle) and innervates via collaterals, among other structures, the paramedian pon- tine reticular formation, the abducens nucleus, and the infe- rior olive. The tectoreticulospinal tract terminates on motor neurons in the rostral spinal cord that supply the cervical musculature.
The inferior colliculus is subdivided into the central nucleus, a laminar nucleus for ascending fibers of the audi- tory pathway (Fig. 1.16b, e and p. 31), the pericentral nucleus for descending fibers of the auditory pathway from the auditory cortex, and the external nucleus for descending fibers from the cortex and thalamus, as well as for afferents from the contralateral inferior colliculus, the trigeminal nucleus, and the solitary tract nucleus. The external nucleus forms a zone between the superior and the inferior nucleus.
The multisensory afferents of this nucleus and its connection to the superior colliculus support the hypothesis that it has an important role in orienting responses to auditory stimuli. The afferent axons from the inferior colliculus converge in the lateral zone and form the brachium of the inferior colliculus.
From here the fibers ascend to the medial geniculate body (Moore and Linthicum 2004).
1.4.7.4 Red Nucleus
Like the pyramidal pathway, the red nucleus controls fine movements of the distal extremities (hand and finger), although
this applies mainly to automatically performed and not to newly learned movements. It represents the largest nucleus of the midbrain, is topographically organized (face dorsal, upper extremities medial, lower extremities ventrolateral), and inter- spersed with numerous bundles of medullated fibers of the brachium conjunctivum, some of which terminate in this nucleus. In addition, roots of the oculomotor nerve on their way to the interpeduncular fossa, as well as the tractus retro- flexus, travel through the red nucleus without terminating there. Within the red nucleus a caudal magnocellular part can be differentiated from a rostral parvocellular one.
The nucleus receives its main inputs from the cerebral cor- tex and the cerebellum, and sends efferent axons to the infe- rior olive and the spinal cord; the cells in the magnocellular part are the origin of the rubrospinal tract. Compared to the situation in monkeys and cats, the rubrospinal tract in humans is only rudimentary (Holstege 1991, Holstege et al., 2004). This topographically organized fiber pathway exits the nucleus medially, crosses in the ventral part of the important ventral tegmental decussation (tegmental decussation of Forel, Fig. 1.14a, b), descends initially in the ventrolateral pons and medulla and from there travels in the dorsolateral funiculus of the spinal cord (Fig. 1.16). Here the areas with representation of the hand and wrist receive the largest number of terminals. The magnocellular part of the red nucleus receives inputs from the motor cortex and is con- nected via reciprocal projections with the emboliform and globosus nuclei of the spinocerebellum.
The size of the parvocellular part of the red nucleus is related to development of the cerebellar hemispheres (neo- cerebellum). It receives inputs primarily from the cerebral cortex that originate from larger areas than those to the magnocellular part. The corticorubral tract descends in the ipsilateral internal capsule to the parvocellular part of the red nucleus. The efferents from the parvocellular part also cross in the ventral tegmental decussation and project via several adjacent mesencephalic structures (nucleus of Darkschewitsch, medial accessory nucleus of Bechterew, interstitial nucleus of Cajal and mesencephalic reticular for- mation) to the inferior olive. From there crossed fibers pass as climbing fibers via the inferior cerebellar peduncle to the cerebellum. These pathways form important neural loops for motor learning.
1.4.7.5 Substantia Nigra
The substantia nigra contains a mixed population of neurons located in the ventral mesencephalon and constitutes the major tissue between the cerebral crus and the red nucleus (Halliday 2004). At approximately the age from 15 to 18 years it becomes strongly pigmented due to the presence of neuromelanin, a metabolic product of dopamine. The dopaminergic part of the substantia nigra is described as
26 1 Neuroanatomy of the Brainstem
Red nucleus Corticonuclear tract
Corticospinal tract Anterior
corticospinal tract Medial
longitudinal fasciculus
Rubrospinal tract
Lateral corticospinal tract Internal capsule Thalamus
III IV
V
VIIXII X XI VI
Red nucleus Parieto- pontine tract
Occipitopontine tract
Fronto- pontine tract Temporo- pontine tract
Corticopontine tract Pontine nuclei
Superior cerebellar
peduncle Middle cerebellar peduncle
Vestibulo- cerebellar tract Inferior cerebellar peduncle
Posterior spinocerebellar tract Anterior spinocerebellar tract Inferior olive
Medial lemniscus Inferior colliculus Lateral lemniscus Spinothalamic tract
Trapezoid body Inferior olive
a
c
e
Red nucleus
Cuneate nucleus Gracile nucleus Central tegmental tract
Red nucleus Medial lemniscus
To cerebral cortex
Spinothalamic tract
Lateral lemniscus
Gracile nucleus
Cuneate nucleus Inferior
colliculus
XII
Corticonuclear tract
Corticospinal tract
Anterior corticospinal tract (uncrossed) Lateral corticospinal tract (crossed)
Red nucleus Rubrospinal tract Medial longitudinal fasciculus IV
V VI VII XII XI III
Superior cerebellar peduncle
Decussation
Corticopontine tract
Pontine nuclei
Inferior cerebellar peduncle
Olivocerebellar tract
Posterior spinocerebellar tract
Inferior olive Dentate nucleus Medial cere- bellar peduncle Red nucleus
b
d
f
Anterior
spinocerebellar tract Cerebral crus
Fig. 1.16 Connections of pathways in the brainstem. (a–c) Lateral view of brainstem connections; (d–f) dorsal view with descending (red) and ascending pathways (dark gray). Pathways descending from the cortex are
shown in (a) and (d), pathways of the spinothalamic tract and the lemniscal system ascending to the cortex are shown in (b) and (e); and connections to the cerebellum in (c) and (f) (modified from Bähr and Frotscher, 2003)
1.4 Internal Architecture 27
the pars compacta and can be divided into a dorsal and a ventral layer. Located ventral to the pars compacta is a third layer, the pars reticulata, a group of unpigmented neurons.
The three layers of the substantia nigra can be further divided into columnar cell groups that have a close topographic relation- ship to the basal ganglia, the thalamus and the brainstem. The cells of the pars reticulata contain GABA and are frequently described as the caudal extension of the internal part of the glo- bus pallidus. The lateral part of the substantia nigra has a visual motor function (Harting and Updyke 2006).
Functionally, the substantia nigra forms an integral part of the basal ganglia, which play a role in the modulation or generation of movement. The striatum (caudate nucleus and putamen) is a central part of the basal ganglia and has reciprocal connections to the dopaminergic pars compacta, and is controlled by striatal activity. The GABAergic cells of the pars reticulata form (via the superior colliculus) the second most important output of the basal ganglia.
The substantia nigra is separated from the red nucleus by the nucleus parabrachialis pigmentosus, a loosely packed dop- aminergic cell group, which is referred to as A10 or the dorsal part of the substantia nigra. All Parkinson disease types, not only the classical form, are characterized by progressive death of dopaminergic cells in the pars compacta of the substantia nigra. Three of the types, progressive supranuclear palsy, cor- ticobasal degeneration, and postencephalitic Parkinson’s dis- ease are also characterized by the loss of non-dopaminergic cells of the pars reticulata (Hardmann et al. 1997).
1.4.7.6 Periaqueductal Gray
Owing to the fact that staining of cells or fibers does not enable the identification of individual cell groups within the periaqueductal gray, staining with neurochemical markers (NADPH diaphorase, NO synthetase, acetylcholine) and examination of their connections are used for this purpose.
The functional mapping studies show that the periaqueductal gray can be divided into quadrants consisting of a dorsome- dial, dorsolateral, lateral and ventrolateral column.
From a neuroanatomical point of view, the subdivisions of the periaqueductal gray represent a relay station for ascending sensory pathways, responsible for the transmis- sion of pain stimuli, as well as for the descending limbic pathways; both of these interact with the ventrolateral col- umn, while the dorsomedial column transmits information to the thalamus and receives afferents from the limbic regions of the cerebral cortex. Conversely, the dorsolateral part is associated with the neighboring intermediate and deeper lay- ers of the superior colliculus, and thereby serves to support the orientation of the body in response to alarm stimuli.
Functionally, the periaqueductal gray is involved in a wide range of coordinated emotional behavior, includ- ing the modulation of pain, cardiovascular regulation,
vocalization, micturition, defence reactions and sexual behavior (Holstege et al. 2004).