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Neuroanatomy, Red Nucleus Cite this Page

Jason Vadhan; Joe M Das.

Author Information and Affiliations In this Page

Last Update: July 24, 2023. Introduction

Structure and Function

Introduction Go to:
Embryology
The Red Nucleus (RN) is a primitive brainstem structure located in the ventral midbrain.
Blood Supply and Lymphatics
Histologically, the RN consists of two distinct structures: a caudal parvocellular red nucleus
(RNp) and a rostral magnocellular red nucleus (RNm).[1][2] Although the origin of the RN is Nerves
not completely understood, studies suggest it can be attributed to the evolutionary development Surgical Considerations
of limbs and locomotion among vertebrates.[3] Specifically, when comparing different species,
Clinical Significance
there is wide variability in both the structure and function of the RN. Generally speaking,
the RNm predominates in lower vertebrates, while the RNp is more prominent in higher species. Review Questions
[2] With regards to quadrupedal mammals (i.e., cats and rats), the RNm is highly developed. References
However, when progressing upward the evolutionary pyramid, the RNm decreases in size and
ultimately bares minimal significant volume or neurological function within the human brain
(conversely, the RNp occupies most of the RN total volume in humans).[1][4][5] Bulk Download
[6] Furthermore, although the two subsections of the RN are virtually undifferentiated in lower Bulk download StatPearls data from FTP
mammals, the human RNm and RNp are so distinct that they are more so considered two
completely independent structures altogether.[2]
Related information
Structure and Function Go to: PMC

As mentioned previously, the RN is subdivided into the RNp and the RNm. Both of these PubMed
neurons are arranged in a somatotopic distribution, with the upper limb corresponding with the
dorsomedial region, and the lower limb correlating with the ventrolateral portion.[7][1] With
regards to the RNm, the contralateral interposed nuclei of the deep cerebellum projects neurons Similar articles in PubMed
that travel directly to the RNm, which thereby gives rise to the rubrospinal tract and [Magnocellular and parvocellular red nuclei.
Anatomico-functional aspects[Rev
andNeurol
relations
(Paris).
with the
1993]
subsequently relays into the spinal cord.[1] Conversely, the RNp receives input from the dentate
cerebellum and other nerve centres].
nucleus within the cerebral cortex as well as the deep white matter of the cerebellum and Functional specialization within the cat red nucleus.
redirects input into the ipsilateral inferior olivary nucleus (commonly referred to as the [J Neurophysiol. 2002]
myoclonic triangle, the Triangle of Guillain-Mollaret, or the dentato-rubro-olivary pathway).[1] Development of the human magnocellular red nucleus:
a morphological study. [Brain Dev. 2006]
It is important to distinguish the subsections of the red nuclei because each possesses a unique
neuronal pathway, and therefore dictates a separate neurologic function. For example, among Review Red nucleus structure and function: from
anatomy to clinical neurosciences.
[Brain Struct Funct. 2021]
quadrupedal animals, the RNm closely mirrors the pyramidal tract when animals navigate
through obstacles and perform various coordinated extremity movements.[8] In upper mammals Review The mammalian red nucleus and its role in
motor systems, including the emergence
[Prog Neurobiol.
of bipedalism
2012]
(such as primates) rubrospinal activity (and therefore RNm activity) influences more primitive and language.
motor activity such as grasping, most prominently among infants.[9] As mentioned previously, See reviews...
the RNm is largely rudimentary in adult humans (and therefore bears a lesser neurologic role), See all...
most likely due to the development (and functional redundancy) of the corticospinal tract as well
as the pyramidal system.[9][10] One interesting correlation to note is that among fetuses and
newborns, who possess a particularly notable magnocellular red neurons, also demonstrate Recent Activity
particularly prominent limb flexor tone.[9] Additionally, anencephalic infants deprived of the Turn Off Clear

cerebral cortex (but still have intact midbrain and therefore, an RN) can exhibit synergistic Neuroanatomy, Red Nucleus - StatPearls
stepping patters, therefore reinforcing the notion that the rubrospinal tract bears functional
responsibility in primitive movements.[11] See more...

In contrast, the RNp provides an important connection between the motor and premotor cortices
as well as the cerebellum, and inputs directly into the inferior olivary nucleus.[9] Therefore, this
subsection of the RN represents an important link in the motor circuit. Although the exact role of
the RNp remains unknown, it is suggested to potentially play a role in complex cognitive-motor
functions by regulating the olivocerebellar tract system.[12][13]

In summary, the parvocellular division of the RN is particularly prominent in the adult human
brain and may play a role in cognitive-motor function, while the magnocellular RN only
demonstrates functional relevance in early development through primitive movements, and
becomes less functionally significant with aging.[9]

Embryology Go to:

To date, there are very few studies exploring the embryonic development of the red neuron.[6]
[2] However, studies that have examined such development noted several consistent findings.
First, initial development commences with cell migration concurrently with the mid-brain from
the cerebellum at around week 7. Around week 8, cells accumulate along the cerebellar
outgrowth, which eventually develops into the dentate nucleus in series with the RN. After that,
RN differentiation commences with RNm formation beginning around 12 weeks.[2] By week
14, large and small neurons are recognizable within the RN and continue to develop into the
RNm and the RNp. Between weeks 18-23, the oculomotor nerve localizes and clusters around
the RN[2] and eventually distributes along the ventrolateral superior cerebellar peduncle from 28
weeks onward. Finally, from weeks 28 to 33, there is a near-linear increase in neuronal size with
regards to gestational age, leading to ultimately a consistent detection of neuro-histology by 33
weeks.[2]

Blood Supply and Lymphatics Go to:

The RN receives blood supply from the Posterior Cerebral Artery (PCA).[14][15][14]

Nerves Go to:

There is an increasing number of studies exploring the relationship between the magnocellular
RN and pain modulation and allodynia,[16][17] most likely via inflammatory cytokine
expression through the JAK/STAT, JNK, ERK signaling cascade.[18][19] As such, previous
studies have demonstrated that spared nerve injury in animal models up-regulate pro-
inflammatory cytokines (such as interleukin-6 and tumor necrosis factor-alpha) within the red
nucleus. Furthermore, the administration of recombinant pro-inflammatory cytokines directly
within the RN can evoke tactile allodynia.[19][20] Conversely, inhibition of such cytokines
can mitigate neuropathic pain[21][22] and relieve subsequent spared nerve injury tactile
allodynia.[23][24][25] The combination of these findings suggests a causal relationship between
the red nucleus and pain modulation.

Surgical Considerations Go to:

Among the most common surgical interventions for Parkinson disease involves targeted deep
brain stimulation of the subthalamic nucleus. This procedure, however, is subject to a high rate
of error.[26][27] One important consideration with regards to this procedure is the close
resemblance, both anatomically and physiologically between the subthalamic nucleus and the
RN, especially among Parkinson disease patients.[27] This close resemblance commonly causes
incorrect lead placement[27][28] and is the reason why over 50% of deep brain stimulation
procedures result in failure.[29]

Clinical Significance Go to:

There are a number of clinical situations that bear relation to the RN and its function. First, as
mentioned previously, there is considerable functional redundancy between the corticospinal
tract and the rubrospinal tract. Therefore, in the case of corticospinal tract injury (such as stroke
or spinal cord injury), neurologic compensation and response take place in the acute setting, by
which the red nuclei undergo remodeling, and increases activity.[30] This upregulation may
provide a small degree of compensation in motor function.[30][31][32][33][34]

Another clinically relevant manifestation with regards to the RN can be seen in patients with
substantial brain damage. Specifically, the involuntary posture that a patient demonstrates can
help localize the lesion of interest. In decorticate rigidity, flexion of the upper extremities
illustrates an intact RN (and rubrospinal tract). If the lesion reaches the RN (and therefore, the
midbrain), the upper extremities demonstrate extended posture, which is referred to as
decerebrate posturing.[35]

The third (and much less common) clinical manifestation regarding direct damage to red nuclei
involves hypertrophic olivary degeneration and ultimately palatal myoclonus (and
dysphagia) [36], by which patients’ diaphragm, laryngeal muscles, as well as the soft palate and
pharyngo-palatine arch move in a rhythmic and involuntary jerking motion.[37]

Fourth, lesions of the RN may lead to various third nerve palsies due to the intimate anatomical
relationship between it and the oculomotor nerve. Specifically, fibers of Cranial Nerve III travel
alongside the RN as it leaves the oculomotor nerve nucleus and passes ventrally through the
midbrain.[38] It is also worth noting that given the close proximity between the dentate nucleus
of the cerebral cortex, the cerebellum, and the inferior olivary nucleus, there are a number of
rare yet academically notable syndromes that manifest secondary to lesions within this network.
There are two specific associated syndromes worth noting, the first is colloquially referred to as
Benedikt Syndrome (paramedian midbrain syndrome), which presents as ipsilateral cranial nerve
III palsy, contralateral hemiataxia with intention tremor, and contralateral hemiparesis.[39]
[40] The second is Claude Syndrome, which encompasses all the features of Benedikt syndrome
as well as an associated asynergy and dysdiadochokinesia due to a lesion of the adjacent superior
cerebellar peduncle.[41]

Fifth, there is a rare autosomal recessive disorder known as Woodhouse-Sakati Syndrome,

characterized by hypogonadism, adolescent-onset diabetes mellitus, hypothyroidism, and
alopecia.[42] Additional neurologic findings include bilateral sensorineural hearing loss in
childhood, mild intellectual disability, and various extrapyramidal findings.[42] These changes
are caused by mutations in the DCAF17 gene. As a result of these changes, there is excess iron
deposition among several structures within the brain, including the substantia nigra, red nucleus,
and dentate nucleus.[43]

Lastly, there is consideration given towards the interplay between the RN and Parkinson disease.
[27] Although the exact mechanism remains unknown, a number of studies have explored the
potential relationships, including the overall RN firing rate in relation to Parkinson disease,
[27] the relationship between iron content of RN and the likelihood of levodopa-induced
dyskinesia development,[44] and the relationship between RN volume and Parkinson disease-
associated motor symptoms.[45][46] Similarly, and as mentioned previously, the functional and
expressive similarities between the RN and the subthalamic nuclei also present difficulties with
regards to treating Parkinson's disease via deep brain stimulation, and also provide obstacles in
better understanding this disease.[27][26] Of related note, the red nucleus (as well as the inferior
olivary nucleus) has been theorized to play a role regarding essential tremor, but still remain in
question.[47]

Review Questions Go to:

Access free multiple choice questions on this topic.

Comment on this article.

Figure

The Mid-brain or Mesencephalon, Transverse section of

mid-brain at level of superior colliculi, Optic Nerve,
Cerebral Aqueduct, Nucleus of oculomotor nerve, Medial
longitudinal fasciculus, Red Nucleus, Tegmentum,
Lemniscus Contributed by Gray's Anatomy (more...)

Figure

The Fore-brain or Prosencephalon, Coronal section of brain

immediately in front of pons, Thalamus, Lateral ventricle,
Caudate nucleus, Internal capsule, Lentiform nucleus,
Claustrum, Insula, Hippocampus, Gyrus dentatus, Red
Nucleus, Fornix, Corpus callosum (more...)

Figure

Red nucleus Image courtesy S Bhimji MD

References Go to:

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Disclosure: Jason Vadhan declares no relevant financial relationships with ineligible companies.

Disclosure: Joe M Das declares no relevant financial relationships with ineligible companies.

Copyright © 2023, StatPearls Publishing LLC.

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