Midbrain (Mesencephalon)

Cerebral peduncles

On the cross-section of the midbrain, we can see that the cerebral peduncles consist of the ventral and dorsal regions. The ventral region of each crus is called the crus cerebri, and contains the white matter from the cortex. The dorsal regions of the crura are continuous with each other and together are called the tegmentum of the midbrain. The tegmentum contains certain neural pathways, reticular formation, and cranial nerve nuclei. The tegmentum is separated from the crura cerebri by the substantia nigra.

Crus cerebri

The crus cerebri is the most ventral area of each cerebral peduncle. It is composed of three descending pathways which have specific arrangement. These pathways are also collectively called the longitudinal pontine fibers:

• Corticospinal and corticonuclear pathways, which travel towards the spinal cord and cranial nerve nuclei, respectively. Together, these pathways occupy the central two-thirds of each crus cerebri.
• Corticopontine pathways, which are divided into the frontopontine and temporopontine tracts based on from which part of the cerebral cortex they originate. The frontopontine tract occupies the medial sixth of ipsilateral crus, while the temporopontine tract composes the lateral sixth of ipsilateral crus.

Tegmentum (Pretectal area)

The mesencephalic tegmentum, also known as the pretectum, is the central part of the midbrain. It contains the reticular and cranial nerve nuclei, as well as several neural pathways. These structures span on various levels of the midbrain, so let’s analyze their anatomy and location.

Midbrain reticular formation

The reticular formation is a network of phylogenetically old nuclei that is in charge of regulating basic and vital autonomic functions. The reticular formation is spread throughout the whole brainstem. The mesencephalic part of the reticular formation lies within two clusters that are found anterolateral to the periaqueductal gray, respectively. Each cluster is divided into three columns with specific functions:

• Gigantocellular reticular nuclei (medial column) - involved in motor coordination
• Raphe nuclei (median column) - involved in pain and mood regulation
• Parvocellular reticular nuclei (lateral column) - involved in the regulation of breathing

Periaqueductal gray matter

Periaqueductal gray (PAG) is a mass of neuronal bodies that encircles the cerebral aqueduct. The main function of periaqueductal gray is to modulate pain by releasing endogenous opioids, such as enkephalin, serotonin, and dynorphin.

The PAG connects to the somatosensory areas of the cerebral cortex, as well as with the lower spinal cord centers. In the broader sense of speaking, PAG is the place where the distinction between the expected and actually perceived pain is made. This function is important for basic survival, as it enables a person to learn about and avoid behaviors that are potentially life-threatening and dangerous.

Cranial nerve nuclei

The nuclei of the oculomotor (CN III), trochlear (CN IV), and trigeminal nerves (CN V) are located near the periaqueductal gray matter.

• The nucleus of oculomotor nerve is a general somatic efferent nucleus. It is located ventral to the periaqueductal gray. This is a motor nucleus that provides the fibers for the innervation of all extraocular muscles except for the superior oblique and lateral rectus muscles.
• The accessory oculomotor nucleus (Edinger-Westphal) is a general visceral efferent nucleus, lying just dorsal to the nucleus of oculomotor nerve. It is a parasympathetic nucleus that innervates the ciliary and sphincter pupillae muscles and enables miosis of the pupil. These nuclei play an important role in pupillary light reflex and accommodation of the eye.
• The nucleus of trochlear nerve is a general somatic efferent nucleus. It is located in the most ventral part of the periaqueductal gray, and its function is to innervate the superior oblique muscle.
• The mesencephalic nucleus of trigeminal nerve is a general somatic afferent nucleus. It extends through the lateral part of the periaqueductal gray, from the pons up to the level of the superior colliculus of the midbrain. The function of this nucleus is to receive the proprioceptive information from the muscles of the face.

Red nucleus

The red nucleus (nucleus ruber) is an ovoid mass located dorsomedial to substantia nigra at the level of the superior colliculus. It bears this name because of the reddish color that this nucleus has on fresh specimens, due to its high iron content.

The red nucleus consists of two parts:

• The caudal (magnocellular) portion
• The rostral (parvocellular) portion

The main inputs to the red nucleus come from the primary somatomotor and somatosensory areas of the cerebral cortex, as well as from the cerebellum. These inputs are carried via the corticorubral and cerebellorubral tracts, respectively.

The major output from the red nucleus is the rubrospinal tract. It originates from the magnocellular part of the nucleus, decussates, and terminates within the cervical segments of the spinal cord. The main function of this tract is to adjust the movements of the upper limbs in order to maintain the balance of the body. For example, the back-and-forth movements of the arm that we make while we walk are regulated by this tract.

The parvocellular part of the nucleus receives the fibers from the dentate nucleus of the cerebellum. It then projects to the inferior olivary nucleus by traveling through the central tegmental tract that passes through the ventral midbrain. The neurons of the inferior olivary nucleus then project back to the cerebellum, forming the cerebello-rubro-olivary circuit. The function of this circuit is to contribute to the cerebellar system of motor control. It is known that the damage of this circuit results in tremor (shaking) and motor discoordination.

Ascending pathways

The midbrain provides the passage for many ascending pathways. Namely, these are the superior cerebellar peduncles, medial longitudinal fasciculus, medial lemniscus, lateral lemniscus, trigeminal lemniscus, and spinal lemniscus.

The superior cerebellar peduncles (brachium conjunctivum) are the paired white matter bundles that connect the cerebellum with the midbrain. They ascend from the cerebellum and enter the midbrain at the level of the inferior colliculi. The fibers are located centrally in the ventral part of the mesencephalic tegmentum. They decussate at the inferior colliculi level, forming a horseshoe-shaped commissure of Wernekinck. After decussating, the fibers divide into ascending and descending bundles.

• The ascending bundle consists of the cerebellothalamic tract and cerebellorubral tracts. The former continues its pathway through the brainstem to reach the ventrolateral nucleus of the thalamus, while the latter synapses with the contralateral red nucleus. A small amount of the ascending fibers synapses with the periaqueductal gray and reticular formation.
• The descending bundle consists of the fibers that synapse with the reticular formation of the pons and medulla, as well as with the olivary nuclei.

The midbrain contains five sensory pathways; one fasciculus and four lemnisci. Namely, they are the medial longitudinal fasciculus (MLF) and the medial, trigeminal, spinal, and lateral lemnisci. The medial longitudinal fasciculus is located just dorsal to the decussation of the superior cerebellar peduncle. This pathway connects the oculomotor, trochlear, abducens, Edinger-Westphal, vestibular, reticular and spinal accessory nuclei. Via these connections, it enables the conjugate eye movements, as well as the associated movements of the head and neck.

The four lemnisci pass through the lateral margin of the tegmentum. From ventral to dorsal, they are distributed in the following order:

• Medial lemniscus - this is a sensory pathway that continues on the dorsal column of the spinal cord, forming the dorsal column-medial lemniscus pathway with it. This sensory system is in charge of passing the information about vibration, slight touch, skin stretch, proprioception, temperature, changes in texture, discrimination, pressure to the thalamus.
• Trigeminal lemniscus (trigeminothalamic tract) - it carries the tactile, pain, and temperature sensations from head to the thalamus.
• Spinal lemniscus (spinothalamic tract) - it conveys pain, temperature, non-discriminative touch and pressure information to the thalamus.
• Lateral lemniscus - it passes the auditory information from the cochlear nucleus to the contralateral inferior colliculus.

Substantia nigra

The substantia nigra is a semilunar lamina of heavily pigmented neurons located between the crus cerebri and the mesencephalic tegmentum. The distinguishable dark color comes from the pigment neuromelanin. The substantia nigra spans all the levels of the midbrain, from the pons to the subthalamus. Functionally, the substantia nigra is a part of the extrapyramidal motor system, through which it contributes to the control of the movements by connecting with the basal ganglia.

The substantia nigra consists of two parts that share different connections with other parts of the nervous system:

• Dorsal pars compacta, composed of neurons that produce the neurotransmitter dopamine. It connects with the striatum via the nigrostriatal pathway and facilitates its activity. The loss of the dopaminergic neurons of the pars compacta plays a central role in the development of Parkinson's disease and other parkinsonian syndromes.
• Ventral pars reticulata, composed of the neurons that mainly produce the inhibitory neurotransmitter GABA. This part of substantia nigra receives the information from the striatum, after which it further projects to the thalamus.

Tectum

The tectum, or the quadrigeminal plate, consists of the two pairs of relay nuclei, collectively called the corpora quadrigemina.

• The superior colliculi are involved in the processing of visual information. They receive afferents mainly from the retina while sending their outputs to the lateral geniculate bodies. The function of the superior colliculi is to facilitate the ocular reflexes that mainly have protective functions, for example, covering your eyes upon a sudden onset of brightness.
• The inferior colliculi are connected with the cochlear nuclei and are involved in the processing of auditory information. They project to the medial geniculate bodies and are involved in reflexive movements provoked by the auditory stimuli. An example of such movement is turning your head towards the source of a sudden and unexpected sound (e.g. explosion).