Cerebellum

The cerebellum, Latin for “little brain,” is located in the posterior cranial fossa, dorsal to the pons and midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem, and its principal role is in the coordination of movements. The cerebellum consists of 3 lobes on either side of its 2 hemispheres and is connected in the middle by the vermis. Three paired peduncles link the cerebellum to the brainstem and diencephalon. Much like the cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex, the cerebellum has a cortex of gray matter Gray matter Region of central nervous system that appears darker in color than the other type, white matter. It is composed of neuronal cell bodies; neuropil; glial cells and capillaries but few myelinated nerve fibers. Cerebral Cortex on the surface.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Overview and Features

  • Cerebellum is Latin for “little brain” and is involved in several functions:
    • Modification of motor output
    • Maintenance of balance and posture
    • Coordination of voluntary movements
    • Motor learning
    • Cognitive functions
  • Located dorsal to the pons and medulla in the posterior cranial fossa
  • Forms the roof of the 4th ventricle
  • Each hemisphere consists of 3 lobes:
    • Anterior lobe: input primarily from the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord:
      • Separated from the posterior lobe by the primary fissure
      • United with the contralateral anterior lobe by the midline vermis
    • Posterior lobe: input from the brainstem and cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex:
      • Separated from the flocculonodular lobe by the posterolateral fissure
      • United with the contralateral posterior lobe by the midline vermis
    • Flocculonodular lobe: input from the vestibular nuclei:
      • Smallest of the 3 lobes, lies superior to the anterior aspect of the posterior lobe, inferior to the anterior lobe, and posterior to the brainstem
      • United with the contralateral flocculonodular lobe by the midline vermis
  • Cerebellum is joined to the brainstem by 3 peduncles that are paired bilaterally:
    • Middle cerebellar peduncle:
      • Conveys information about voluntary motor activities
      • Connects cerebellum to the basal pons
      • Located laterally
      • Largest of the 3 peduncles
    • Inferior cerebellar peduncle:
      • Consists of afferent and efferent fibers that carry proprioceptive information to and from the body and vestibular system
      • Connects cerebellum to the medulla
      • Located medially to the middle peduncle
    • Superior cerebellar peduncle:
      • Afferent and efferent fibers are engaged in motor control.
      • Connects cerebellum to the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem and thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus
      • Located superior to the other peduncles
  • Cerebellar blood supply is via 3 bilateral arterial vessels:
    • Superior cerebellar artery (SCA)
    • Anterior inferior cerebellar artery (AICA)
    • Posterior inferior cerebellar artery ( PICA Pica Pica is an eating disorder characterized by a desire or recurrent compulsion to eat substances that are nonnutritive and not food. These compulsions and ingested substances are inappropriate for age or culture. Pica)
  • Cerebellar embryology: dorsal surface ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation → neural tube → rhombencephalon → metencephalon → cerebellum

Cerebellar peduncles and their connections:

  • Midbrain/ thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus ↔ superior cerebellar peduncle ↔ cerebellum
  • Basal pons → middle cerebellar peduncle → cerebellum
  • Medulla ↔ inferior cerebellar peduncle ↔ cerebellum

Internal Circuitry and Organization

Cerebellar cortex

The majority of neuronal cell bodies are located in the cortex, which can be divided into 3 layers:

Granular cell layer:

  • Innermost layer
  • Consists primarily of 2 cell types:
    • Granule cells:
      • Excitatory cells
      • Glutamate is the key neurotransmitter.
      • Axons of granule cells are parallel fibers that stimulate Purkinje cells.
    • Golgi cells:
      • Inhibitory cortical interneurons
      • Glycine is the key neurotransmitter.
      • Axons terminate on dendrites of granule cells.

Purkinje cell layer:

  • Middle layer
  • Consists of 2 cell types:
    • Purkinje cells:
      • Largest cells in the cerebellar cortex
      • Inhibitory and GABAergic: inhibit neurons in the deep cerebellar nuclei
      • Only output neurons of the cerebellar cortex
      • Arranged in a monolayer
      • Axons advance to cerebellar nuclei and the molecular layer.
    • Bergmann glia:
      • Specialized astrocytes
      • Closely associated with Purkinje cells

Molecular layer:

  • Outermost layer of the cerebellar cortex
  • Location of Stellate and Basket cells, which are important cortical interneurons
Cerebellar-cortex

Cerebellar cortex and the 3 layers, namely the molecular layer, Purkinje cell layer, and granular cell layer. Note the bodies of Purkinje cells situated in the Purkinje layer while their dendrites project into the molecular layer.

Image by Lecturio.

Cortical interneurons

Cortical interneurons can be divided into 2 categories:

  • Inhibitory glycinergic cells from the granular layer:
    • Golgi cells:
      • Located primarily in the granular layer
      • Axons terminate on dendrites of granule cells.
    • Purkinje cells:
      • Located in the Purkinje layer
      • Axons terminate on the cerebellar nuclei and molecular layer.
  • Inhibitory GABAergic cells from the molecular layer:
    • Stellate cells:
      • Located in the upper molecular layer
      • Axons terminate on the dendrites of Purkinje cells.
    • Basket cells:
      • Located in the deep molecular layer
      • Axons terminate on the dendrites of Purkinje cells.

Cerebellar nuclei

Cerebellar nuclei consist of 4 halved areas:

  • Nucleus dentatus:
    • Located in the center of the cerebellum
    • Most prominent nucleus
    • Efferent → ventral anterior (VA) and ventral lateral (VL) nuclei of the thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus
  • Nucleus interpositus:
    • Consists of 2 nuclei:
      • Nucleus emboliform: located medial to the nucleus dentatus
      • Nucleus globosus: located medial to the nucleus emboliform
    • Efferent → red nucleus of the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem and reticular formation
  • Nucleus fastigii:
    • Located most medially
    • Efferent → vestibular nucleus
  • Primary output is to the glutamatergic relay neurons.
  • Primary input:
    • Inhibition from Purkinje cells
    • Excitation from mossy and climbing fibers
Location of the nuclei within the cerebellum

Location of the nuclei within the cerebellum
From lateral to medial: dentate nucleus, interposed nucleus (consisting of the emboliform and globose nuclei), and most medially, the fastigial nucleus

Image by Lecturio.

Cerebellar Connections

Cerebellar afferent pathways

Many afferents pass through the 3 cerebellar peduncles to the cerebellar cortex. There are 2 extracerebellar excitatory glutamatergic afferent systems:

  • Mossy fibers:
    • Originate in the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord and brainstem
    • Synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission on Purkinje cells
  • Climbing fibers:
    • Originate in the contralateral inferior olivary nucleus within the medulla
    • Synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission on Purkinje cells

Cerebellar efferent pathways

Efferent pathways of the cerebellum pass from the cerebellar nuclei to the following:

  • Thalamus
  • Vestibular nuclei
  • Red nucleus
  • Reticular formation

Cerebellar regions

The cerebellum can also be divided into 3 regions based on connections:

  • Vestibulocerebellum:
    • Function: maintenance of posture and vestibular reflexes
    • Inputs: vestibular nerve
    • Outputs:
      • Cerebellovestibular tract
      • Vestibular nucleus
      • Spinal cord
  • Spinocerebellum:
    • Function:
      • Integration of sensory input with motor output
      • Adaptive coordination of muscle movements
    • Input: spinocerebellar tract
    • Outputs:
      • Reticular formation
      • Red nucleus
      • Spinal cord
  • Pontocerebellum:
    • Function:
      • Timing and planning of movements
      • Cognition
    • Input: pontocerebellar tract
    • Output:
      • Thalamic nuclei (VA and VL)
      • Cortex
      • Spinal cord

Clinical Relevance

  • Brainstem: consists of the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem, pons, and medulla oblongata. The brainstem is a stalk-like structure that connects the cerebrum with the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord and is a major relay station for sensory, motor, and autonomic information. All cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. Overview of the Cranial Nerves except I and II are found in the brainstem and are topographically arranged so that motor nuclei are medial to the sensory nuclei. The brainstem also plays a critical role in the control of cardiac and respiratory function, consciousness, and the sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep cycle.
  • Chiari malformation: Arnold- Chiari malformations Chiari Malformations Chiari malformations (CMs) are a group of central nervous system (CNS) conditions characterized by the underdevelopment of the posterior cranial fossa with subsequent protrusion of neural structures through the foramen magnum. Chiari Malformations are a group of congenital abnormalities that are associated with a bony base of the cranium causing limitation of space in the posterior fossa, thus affecting the cerebellum, brainstem, and upper spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord.
  • Embryologic development: Before the brain reaches the phase when it looks like the organ, there are several complex processes that occur. Beginning with neurulation Neurulation An early embryonic developmental process of chordates that is characterized by morphogenic movements of ectoderm resulting in the formation of the neural plate; the neural crest; and the neural tube. Improper closure of the neural groove results in congenital neural tube defects. Gastrulation and Neurulation, the neural tube and neural crest cells allow the developing embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week to form the central and peripheral nervous systems. The face starts to develop from the 4th week. A recognizable face can be seen from the 14th week due to the formation of the frontonasal, medial, lateral, and mandibular prominences.
  • Friedreich ataxia: occurs due to the expansion of the GAA repeat in the FXN gene. Affected individuals present with ataxia, weakness, absent reflexes, and dorsiflexion of the toes. Late atrophy of the cerebellum and a thin cervical spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord can be seen on MRI.

References

  1. Schijman, E. (2004). History, anatomic forms, and pathogenesis of Chiari I malformations. Childs Nerv Syst. 20, 323–328. https://doi.org/10.1007/s00381-003-0878-y
  2. Khoury, C. (2020). Chiari malformations. UpToDate. Retrieved September 13, 2021, from https://www.uptodate.com/contents/chiari-malformations
  3. Abd-El-Barr, M.M., Strong, C.I., Groff, M.W. (2014). Chiari malformations: diagnosis, treatments and failures. J Neurosurg Sci. 58, 215–221. https://pubmed.ncbi.nlm.nih.gov/25418275/
  4. McClugage, S., Oakes, J. (2019). The Chiari I malformation. JNSPG 75th Anniversary Invited Review Article. https://doi.org/10.3171/2019.5.PEDS18382
  5. Langridge, B., Phillips, E., Choi, D. (2017). Chiari Malformation Type 1: A systematic review of natural history and conservative management. World Neurosurg. 104, 213–219. https://pubmed.ncbi.nlm.nih.gov/28435116/
  6. Warner, W.C., Sawyer, J.R. (2017). Scoliosis and kyphosis. In Azar F.M., et al. (Eds.), Campbell’s Operative Orthopaedics. pp. 1897–2120.e26. https://www.clinicalkey.es/#!/content/3-s2.0-B9780323374620000446

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