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Midbrain (Mesencephalon)

Midbrain (Mesencephalon)

The midbrain, or mesencephalon, is the most rostral part of the brainstem that connects the pons and cerebellum with the forebrain. For most of its part, the midbrain sits in the posterior cranial fossa, traversing the hiatus of the tentorium cerebelli.

The midbrain is the shortest part of the brainstem. However, it contains many important structures that make it essential for the proper functioning of the body:

This article will discuss the anatomy and function of the midbrain (mesencephalon).

Key facts about the midbrain
Definition The initial part of the brainstem that connects the pons with the forebrain
Parts Tectum (roof/quadrigeminal plate)
Cerebral peduncles
- Crus cerebri
- Tegmentum
- Substantia nigra
Nuclei and other gray matter Motor nucleus of oculomotor nerve, accessory motor nucleus of oculomotor nerve (Edinger-Westphal), nucleus of trochlear nerve, mesencephalic nucleus of trigeminal nerve; red nucleus; substantia nigra; peraqueductal gray matter
Tracts Ascending: superior cerebellar peduncle, medial longitudinal fasciculus, spinothalamic tract (spinal lemniscus), medial lemniscus, trigeminothalamic tract (trigeminal lemniscus), lateral lemniscus
: corticospinal pathway, corticobulbar pathway, corticopontine pathway
Function Eye movement, ocular and auditory reflexes, breathing, pain modulation, mood regulation, enables the passage of the major ascending and descending pathway
  1. Gross anatomy 
  2. Anterior (ventral) surface
  3. Posterior (dorsal) surface
  4. Internal anatomy
    1. Cerebral peduncles
    2. Crus cerebri
    3. Tegmentum (Pretectal area)
    4. Substantia nigra
    5. Tectum
  5. Blood supply
  6. Functions overview
  7. Clinical relations
    1. Infarction of the midbrain
    2. Parinaud’s syndrome
    3. Weber’s syndrome
    4. Argyll Roberston pupil (“prostitute’s pupils”)
  8. Sources
+ Show all

Gross anatomy 

The midbrain lies between the thalamus (rostrally) and pons (caudally). Lateral sides of the midbrain are covered and hidden by the hippocampal gyri of the brain.

Anterior (ventral) surface

The anterior surface of the midbrain is marked by the two stalks called the cerebral peduncles. The peduncles are composed of many pathways that travel between the cerebral cortex and spinal cord.

As the peduncles converge caudally towards the pons, they bound a fossa on the anterior surface of the midbrain, called the interpeduncular fossa. The floor of this fossa is formed by the posterior perforated substance, which is a layer of gray matter pierced by the branches of the posterior cerebral artery that supply the midbrain. The contents of the interpeduncular fossa are the following:

  • The terminal bifurcation of the basilar artery into the posterior cerebral arteries
  • The posterior communicating arteries
  • The emerging roots of the oculomotor nerve (CN III)

The midbrain is closely related to the optic tract. The tract horizontally crosses the crura cerebri and winds around them to reach the posterior surface of the midbrain.

Posterior (dorsal) surface

The posterior surface of the midbrain is called the tectum, or roof, of the midbrain. The tectum features four tubercles on its surface which lie inferior to the pineal gland. The upper pair of tubercles are the left and right superior colliculi, while the lower pair are the left and right inferior colliculi. Because of this arrangement, the tectum is also called the quadrigeminal plate, while the colliculi are collectively known as the corpora quadrigemina. The colliculi are separated from each other by the cruciform sulcus. Rostrally, the sulcus extends from the depression of the pineal gland, while its caudal end is continued by the frenulum of the superior medullary velum. The frenulum separates the inferior colliculi one from the other. The trochlear nerve (CN IV) can be seen emerging from either side of the frenulum.

Although we’ll discuss them more later, let’s make a note that the superior colliculi contain the nuclei that are involved in the visual responses, while the inferior colliculi are involved in the auditory pathway.

Internal anatomy

The midbrain consists of two major parts: cerebral peduncles and tectum. The cerebral peduncles consist of the crura cerebri and tegmentum. They are separated from each other by a darkened stripe called the substantia nigra. The dorsal part of the tegmentum is traversed by the cerebral aqueduct, which connects the third and fourth ventricles of the brain. The tectum lies dorsal to the tegmentum and cerebral aqueduct, and it contains the nuclei of the superior and inferior colliculi.

Sagittal view of brainstem structures

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.


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).

Blood supply

The tectum of the midbrain receives its blood supply from the superior cerebellar artery. The central part of the tegmentum is supplied by the posterior cerebral artery and paramedian branches of the basilar artery, while the most lateral parts of the midbrain are nourished by the posterior cerebral artery solely.

Functions overview

As we’ve had the chance to see, the midbrain contains many important structures that facilitate our daily functioning. Let’s just recap the main functions of the midbrain:

  • The midbrain provides the passage for the main descending pathways of the cerebral cortex. Namely, the corticospinal and corticobulbar tracts that enable us with the voluntary movement of the head and body.
  • It acts as a conduit for the main ascending pathways from the spinal cord which carry the sensory stimuli from the body and head to the brain. Namely, these are the medial, lateral, spinal, and trigeminal lemnisci.
  • It houses the mesencephalic portion of the reticular formation which, together with other parts of the brainstem, controls the pain, mood, and breathing.
  • Promotes survival instincts by facilitating the recognition of potentially dangerous behaviors.
  • Housing the substantia nigra, it contains a part of the extrapyramidal motor system and thus is involved in the control of the voluntary movements.
  • It enables the movements of the eye by housing the nuclei of the oculomotor and trochlear nerves. Moreover, it facilitates the coordinated functioning of these nuclei.
  • Connecting with the auditory and visual nuclei, it enables the auditory and ocular reflexive movements.

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