The Mesencephalon

Viewed from the front, the midbrain is dominated by the cerebral peduncles, the crura cerebri – large bundles of fibers that conduct signals from the cortex to the spinal cord and to the pons and cranial nerve nuclei. Descending pathways from almost all parts of the cerebral cortex run neatly through them: on the inside, mainly fibers from the frontal lobe; on the outside, those from the parietal, temporal, and occipital lobes; and in the middle, the pyramidal tract, which controls voluntary motor function. The head and face are represented more on the inside, the legs and feet on the outside – like a small “homunculus”.

From behind, two pairs of mounds can be seen, collectively known as tectum (or lamina tecti, or lamina quadrigema). The upper mounds, the colliculi superiores, receive direct inputs from the retina of the eye via the optic nerve and visual tract. This primarily involves information about rapidly changing stimuli – i.e., movement. This could be a moving car that we follow with our eyes, or a branch that is about to hit our face, causing us to reflexively close our eyes to protect them. Saccades – the rapid eye movements that you are making right now, for example, while reading these words – are also prepared here, with the colliculi selecting the next fixation targets. The actual eye movements then occur in a network that extends from the frontal visual area of the cerebral cortex to the gaze centers in the pons (horizontal saccades) and midbrain (vertical saccades) to the oculomotor nuclei.

Looking at the midbrain from the front, we see the third cranial nerve, the oculomotor nerve, emerging between the cerebral peduncles. The deficits associated with damage to the upper colliculi are correspondingly similar: it is no longer possible to follow an object with the eyes, although all visual stimuli continue to be perceived and processed.

The inferior colliculi, the lower mounds, serve as a switching point for most of the fibers of the auditory pathway. The signals run from here directly to the medial geniculate body of the thalamus and from there on to the primary auditory cortex. This central location of the inferior colliculi in the auditory pathway means that damage to them can lead to reduced hearing ability. Since the inferior colliculi also send signals to the superior colliculi – and vice versa – this enables the reflexive integration of both sensory modalities. And we automatically look in the direction of a loud noise.

The trochlear nerve (IV) is the only cranial nerve that exits at the back of the brainstem – directly below the inferior colliculi.
 

The cerebral peduncles at the front and the four mounds at the back are two of the three layers into which the midbrain is divided. Between these two lies the tegmentum, which contains numerous important nuclei and core areas. Once again, vision is functionally part of this: the oculomotor nuclei, the oculomotor nerve (III) and the trochlear nerve (IV). They control six muscles per eye, which requires very complex interconnection. While vertical eye movements are controlled by the midbrain, horizontal movements are primarily triggered in the pons. Closely related to this is the Edinger-Westphal nucleus, which contains parasympathetic fibers for the pupil response. The pupillary light reflex runs afferently via the optic nerve (nervus opticus, II) and the thalamus, while the efferent control of the pupil muscles is via the oculomotor nerve (III).

But there are also structures beyond vision. One example is the substantia grisea periaqueductalis, or periaqueductal gray matter. It gets its name because the aqueduct, the aqueductus mesencephali, flows directly through this gray matter. It is a central hub for the suppression of pain and becomes active primarily in dangerous situations: pain is then “blocked out” so that escape or defense reactions remain possible.

Another important nucleus in the midbrain is the red nucleus, or Nucleus ruber. It owes its red color to its high iron content. The nucleus ruber belongs to the extrapyramidal motor system, meaning it performs motor tasks that are not negotiated via the pyramidal tract. It is part of a neural loop between the olive and the cerebellum. In the past, its failure was directly equated with what is known as intention tremor – a tremor that becomes stronger the closer a movement gets to its target. Today, we know that lesions in this area tend to lead to a more complex picture: The Holmes tremor, which combines elements of resting, holding, and intention tremor. This illustrates the close cooperation between the midbrain and cerebellum in controlling movement.

The locus coeruleus – the blue spot – owes its dark bluish color to the pigments in its cells. These produce norepinephrine, a stress hormone, which is why, despite its beautiful name, the locus coeruleus is not only considered an arousal system – in connection with the reticular formation (RF) – but also an alarm system. And as we know, too much alarm, too much stress, and too much noradrenaline do not have a positive effect on physical and mental health.

The neurotransmitter serotonin, on the other hand, has little to do with stress. On the contrary, it is involved in falling asleep and maintaining a delicate balance of emotional equilibrium. And it is indeed a balance, because too much serotonin is just as harmful as too little. The only location of serotonin production in the brain is the raphe nuclei, which form the innermost area of the reticular formation. From here, they release their valuable cargo into large parts of the brain, especially the limbic system.

At the top of the midbrain, the substantia nigra, or black substance, is located. It owes its name to a high melanin content in the cell nuclei. And its fame to Parkinson's disease: since it sits in the middle of a network of systems that connect and coordinate movements, its failure has fatal consequences for the initiation of movement and the basic drive to move. The neurotransmitter of the substantia nigra is dopamine – and it is these dopaminergic neurons that die in Parkinson's disease. Up to 70 percent of these cells can die before symptoms become apparent.

The reticular formation runs through the entire brain stem – an entire network of interconnected nuclei that have many different tasks. We have already mentioned the arousal center – more precisely, the ascending reticular activating system (ARAS) –which increases activity in the thalamus and cortex, ensuring not only wakefulness but also consciousness. Damage to this area can lead to coma, although other parts of the reticular formation responsible for respiration and circulatory functions keep the organism alive.

First published on September 8, 2011
Last updated on September 20, 2025