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Histology of the Cerebellum

Aristotle first described the cerebellum way back in the fourth century BC. He detailed a structure located at the back of the brain that shared some similarities to the brain, but noted it differed in form and size.

He therefore coined this structure ‘parencephalis’ in Ancient Greek, the Latin equivalent of which translates literally as ‘little brain’, a phrase which is still used to this day when referring to the cerebellum.

The cerebellum, located dorsal to the pons and the medulla, is one of the primary structures of the hindbrain. It lies under the occipital and temporal lobes of the cerebral cortex. The cerebellum is an integral structure in transmitting sensory signals to the motor portion of the brain.  It contributes to motor function by controlling muscle coordination, equilibrium and posture.

Cerebellum - histological slide

Embryology

The neural plate, derived from the thickening of ectodermal tissue, is the precursor for all components of the central nervous system. Through a process called neurulation the neural plate folds during the fourth week of gestation to become the neural tube. The rostral portion of the neural tube divides into the prosencephalon (forebrain), mesencephalon (midbrain) and rhombencephalon (hindbrain). The rhombencephalon further divides into the metencephalon and myelencephalon. The cerebellum is derived from the dorsal part of the metencephalon, specifically the alar plate, and the neural folds.

Recommended video: Cerebellum
Anterior and superior views of the cerebellum.

Neurons found in the cerebellum are derived from two germinal zones; the ventricular zone and the rhombic lip. The ventricular zone is the neuroepithelium of the alar plate which later develops into the roof of the fourth ventricle. Purkinje cells,, Golgi cells, stellate cells, basket cells and candelabrum cells are just some of the neurons derived from this particular zone.  

Neurons derived from the rhombic lip include large neurons of the cerebellar nuclei, unipolar brush cells and granule cells.

These 2 groups of neurons are distinguishable by the neurotransmitter they release. Neurons from the ventricular zone are inhibitory GABAergic neurons, while those from the rhombic lip are excitatory glutamatergic.

Gross Anatomy

The cerebellum is located in the posterior cranial fossa and lies dorsal to the pons and medulla, from which it is separated by the fourth ventricle. There are 2 major  parts to the cerebellum, the cerebellar deep nuclei and the cerebellar cortex.

Cerebellum - medial view

Output from the cerebellum originates solely in the deep nuclei, where almost all of the neurons of the cerebellum reside. The cerebellum is divided into three subdivisions by two fissures that travel mediolaterally. The flocculonodular lobe is separated from the corpus cerebelli by the posterolateral fissure, while the primary fissure divides the corpus cerebelli into the anterior and posterior lobe.

Flocculonodular lobe - ventral view

The cerebellum can also be divided sagittally. Located along the midsagittal plane of the cerebellum in the cortico-nuclear zone is the vermis. The intermediate zone lies directly lateral to the vermis, while the lateral hemispheres lie lateral to the intermediate zone. The two hemispheres have a deeply folded appearance.

Vermis - dorsal view

As previously mentioned, all outgoing motor signals from the cerebellum originate in the deep nuclei and the nearby vestibular nuclei. The 4 cerebellar deep nuclei include:

  • the fastigial
  • the emboliform
  • the globose
  • the dentate nuclei

Fastigial nuclei

Three distinct fiber bundles carry all signals into and out of the cerebellum, these include the superior, middle and inferior cerebellar peduncles.

Histology

After slicing the cerebellum, it bears a similar resemblance to a cauliflower. This is due to the stemmed appearance of the white matter coated by the outer grey matter of the cortex. When viewing a histological section of cerebellar tissue under the microscope, the lobulations and folia of the cerebellum are immediately evident.

These folia are the leaflike gyri of the cerebellar cortex. The extensive vascular supply will also be evident, as a high blood flow is required to meet the demands of the cerebellum’s neural activity. The pia mater, the innermost layer of the meninges, which covers and protects the cerebellum is also likely to appear surrounding the perimeter of this structure in a stained section.

Pia mater - histological slide

Cerebellar Cortex

As previously mentioned, the grey matter of the cerebellum is also referred to as the cortex and may be split into three layers; the outer molecular layer, the middle layer of Purkinje cells and the inner granular layer. There are many neurons, glial cells and fibers located in the cortex which all contribute to the motor functions of the cerebellum.

Granular Layer

The inner granular layer contains many, tightly packed granule cells and Golgi type II cells. Granule cells, which are among the smallest neurons in the brain almost 5μm in diameter with round to oval in shape, usually represent the extensions of the mossy fibers. Their axons extend into the outer molecular layer where they branch in  T shape forming parallel fibers and synapse with the dendrites of Purkinje, basket and stellate cells.

Granular cell layer - histological slide

The nuclei of these granule cells generally stain dark, giving the whole granular layer a darker appearance compared to the white matter and molecular layer of the cortex. Golgi cells are also scattered throughout the granular layer, with their dendrites branching out in the molecular layer, while their axons synapses with the granule cells.

Granule cells - histological slide

Purkinje Cell Layer

The middle layer (Purkinje cell layer) consists of a single layer of large pear-shaped Purkinje cells. Their cell bodies are largest in the cerebellum with unique and distinct appearance. The dendrites of these cells reside in the molecular layer, while their axons project deep through the granular layer and synapse into the deep nuclei of cerebellum.

Purkinje cell layer - histological slide

Molecular Layer

The outer molecular layer is synaptic and therefore contains many axons of granule cells and and dendrites of the Purkinje cells with least density of cells. Superficially located stellate cells and basket cells are found in this layer. The stellate cells usually bear short dendrites in which make contact with small number of Purkinje cell dendrites. In comparison, basket cells have extensive dendritic processes that can make contact with much larger number of Purkinje cells. Both cells receive excitatory input from the parallel fibers and in turn exhibit inhibitory influence on the Purkinje cells

Molecular layer - histological slide

Cerebellar Medulla

The inner medulla of white matter does not contain any cell bodies and therefore will stain a lighter colour in comparison to the grey matter cortex. It contains nerve fibers, supporting neuroglial cells and small blood vessels.

Clinical Notes

Medulloblastoma

Medulloblastoma is the most common malignant childhood brain tumor and is usually referred to as the collection of clinically and molecularly diverse tumour subtypes. These tumours arise within the cerebellum with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype). It occupies the fourth ventricle and can be removed through midline suboccipital approach.

Ataxias

Due to the motor control functions of the cerebellum, lesions result in a range of movement disorders, known as ataxias. Lesions in the cerebellar hemispheres cause limb ataxia of the ipsilateral side, while lesions of the vermis cause truncal ataxia. There a number of different types of ataxia including:

  • gait ataxia
  • acute-onset ataxia
  • subacute ataxia
  • episodic ataxia
  • chronic progressive ataxia

People with cerebellar ataxia generally present  with poor balance, difficulty turning and lurching from side to side while walking.

Histology of the Cerebellum - want to learn more about it?

Our engaging videos, interactive quizzes, in-depth articles and HD atlas are here to get you top results faster.

Sign up for your free Kenhub account today and join over 1,050,178 successful anatomy students.

“I would honestly say that Kenhub cut my study time in half.” – Read more. Kim Bengochea Kim Bengochea, Regis University, Denver

Show references

References:

  • Marshall L.H., Magoun H.W. The Cerebellum. Discoveries in the Human Brain. Humana Press(1998), p177-198.
  • Balaei M.R, Ashtari N, Bergen H. The Embryology and Anatomy of the Cerebellum. Development of the Cerebellum from Molecular Aspects to Disease. Springer (2017), p33-43.
  • Pocock G et al. Human Physiology 4th Editions (2013). Oxford p166
  • S. Standring, Ph.D. et al: Gray’s Anatomy: The Anatomical Basis of Clinical Practice, 41st Edition, Elsevier (2015), p. 353
  • Knierim J. Cerebellum, Neuroscience Online. http://neuroscience.uth.tmc.edu/s3/chapter05.html (Accessed 12th October 2017)
  • Ross M. H., Pawlina W.: Histology: A text and atlas: With Correlated Cell and Molecular Biology, 6th edition, Lippincott Williams & Wilkins

  • Young B., Woodford P., O’Dowd G.: Wheater’s Functional Histology: A Text and Colour Atlas, 6th edition, Churchill Livingstone Elsevier

  • Mescher Anthony L.: Junqueira’s Basic Histology: Text and Atlas, 13th edition, McGraw-Hill Education
  • William K. O, Patrick C. N. Netter's Essential Histology, ClinicalKey 2012 Netter Basic Science Series Saunders W.B.illustrated.Elsevier Health Sciences, 2013
  • John M, Anne F. Clinical Neuroanatomy: A Neurobehavioral Approach.illustrated. Springer Science & Business Media, 2007
  • Gibson P et al. Subtypes of medulloblastoma have distinct developmental origins. 2010. Nature 468, 1095–1099

Article, Review and Layout:

  • Martha Byrne
  • Uruj Zehra
  • Adrian Rad

Illustrators:

  • Cerebellum - histological slide - Smart In Media
  • Cerebellum - medial view - Paul Kim
  • Flocculonodular lobe - ventral view - Paul Kim
  • Vermis - dorsal view - Paul Kim
  • Fastigial nuclei - Paul Kim
  • Pia mater - histological slide - Smart In Media
  • Granular cell layer - histological slide - Smart In Media
  • Granule cells - histological slide - Smart In Media
  • Purkinje cell layer - histological slide - Smart In Media
  • Molecular layer - histological slide - Smart In Media
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