2017 Group Project 6
|2017 Student Projects|
Basic anatomy of the Cerebellum
Neural development is one of the earliest systems to begin and the last to be completed after birth due to its highly complex structure. The first step in neural development occurs at the end of week 3 and involves the neural groove fusing to form the neural tube, which then folds to form the cranial and caudal region of the embryo, and ultimately form the cerebellum  . There is a high chance of neural dysfunction and defects during the fetal neural development particularly due to the long development time frame and the need of certain nutrients such as folic acid to successfully close the tubes. Neural tube defects (NTDs) such as spina bifida and anencephaly can arise if the tubes do not close effectively.
There are 3 major cortical layers of the cerebellum: the molecular layer, the purkinje cell layer, and the granule cell layer. The molecular layer contains basket cells, stellate cells and the purkinje cell and Golgi cell dendrites. The purkinje cell layer contains purkinje cell bodies and Bergmann glia. The granule cell layer contains granule cells, mossy fibers, and Golgi cell bodies. http://neurotransporter.org/Cerebellum.html z5177699
Discovered by Jan Evangelista Purkinje in 1837, purkinje cells are inhibitory neurons found in the outside layer of the cerebellum. They receive signals from the granule cell parallel fibers and the superior olive and send inhibitory signals to the deep nuclei in the white matter region via GABA signaling. Purkinje cells have a large branching network of dendrites which allows them to be identified by their morphology. z5177699
Named for their small cell body, cerebellar granule cells of were discovered by Camillo Golgi and Ramon y Cajal in 1899. Cerebellar granule cells are the most numerous cell type in the human brain. They receive signals from mossy fibers of the pons and synapse on the fast network of dendrites of the pyramidal cells. Cerebellar granule cells are glutamatergic and the only excitatory neurons found in the cerebellum. https://link.springer.com/referenceworkentry/10.1007%2F978-94-007-1333-8_31 z5177699
There are four different deep nuclei of the cerebellum: the dentate, interpositus, fastigial, and vestibular nuclei. The dentate nucleus receives signals from the lateral purkinje cells, the interpositus nucleus receives signals from the intermediate purkinje cells, the fastigial nucleus receives signals from the medial purkinje cells, and the vestibular nucleus receives signals from the flocculonodular purkinje cells. The deep nuclei integrate the inhibitory signals from the purkinje cells and the excitatory signals from the mossy and climbing fibers to determine their output signals. http://www.neuroanatomy.wisc.edu/cere/text/P5/intro.htm
Glial cells of the cerebellum were described by Ramon y Cajal in 1911. He divided them into 3 main categories: the glia of the white matter, the astrocytes of the granule cell layer, and the Bergmann glia of the Purkinje cell layer.
Also known as Goligi epithelial cells, Bergmann glia are unipolar astrocytes that have cell bodies located in the Purkinje cell layer and long processes projecting into the molecular layer. The Bergmann glia's processes interact with the dendrites of Purkinje cells at synapses with parallel and climbing fibers. Bergmann first characterized the long processes of cells he saw in the cerebellum of cats, dogs, and humans in 1857. Ramon y Cajal later described these cells as "epithelial cells with Bergmann fibers," giving the glia their name. https://link.springer.com/content/pdf/10.1046%2Fj.0022-7722.2002.00021.x.pdf
Oligodendrocytes are glia found primarily in the white matter of the cerebellum. These glial cells form the fatty myelin sheath that gives the white matter its color.
Early Brain Structure
z5114433 - primary - secondary - ventricles
z5113034 The cerebellum is supplied by three bilateral pairs of arteries. Most superiorly, there is the aptly named superior cerebellar artery (SCA). Moving inferiorly, there are the left and right anterior inferior cerebellar arteries (AICA) and posterior inferior cerebellar arteries (PICA). The SCA arise from the first bifurcation of the Basilar Artery, directly inferior to the Posterior Cerebral Artery. The AICA are the most inferior branch that arises from the Basilar Artery, and the PICA arise from the left and right Vertebral Arteries. The Vertebral Arteries are two paired arteries that join to form the Basilar Artery.
The PICA and AICA combine to supply the inferior half of the cerebellum while the SCA supplies the majority of the superior half. The center of the cerebellum is a region of large variance with regards to the exact vasculature, as it differs between individuals. http://www.ajnr.org/content/ajnr/8/2/199.full.pdf USE THE IMAGE HERE
(find images of the visualiation of the foetal cerebellum)
As the neural tube folds, the anterior portion develops the three brain vesicles; prosencephalon, mesencephalon and rhombencephalon. The rhombencephalon then further divides into the mesencephalic and myelincephalic vesicles on embryonic day 9. The neural tube failure to close then creates a gap along the dorsal sides and this produces a mouth-like structure as the tube bends to establish the pontine flexure. The pontine flexure further deepens bringing the mesencephalon (midbrain) closer to the primordium of the cerebellum (metencephalon); anterior aspects of the myelincephalon (brain stem) fold underneath developing the cerebellum plate  Further development of the cerebellum begins between days 40 and 45 and it arises mostly from the metencephalon however the rhombic lips also contributes. The roof plate which is derived from the dorsal part of the alar plate thickens during development to become the cerebellum. The regulation of patterning involved when he primary fissure deepens by the end of the third month and divides the vermis shows to be particularly important for development. The two lateral bulges are separated into the cranial anterior lob and caudal middle lobe. As the lobes divide further into lobules, fissures are formed and this continues throughout embryonic, fetal and postnatal life, thus increasing the surface area of the cerebellar cortex. The most primitive part of the cerebellum to form is the flocculonodular lobe, which is derived from separation of the first transverse fissure and this functions to keep connections with the vestibular system and it is also concerned with subconsciously controlling equilibrium. The flocculonodular lobe is separated from another crucial part of the cerebellum, corpus cerebelli, by the posterolateral fissure.
The cerebellum has a very basic structure consisting 2 principal classes of neurons and 3 layers, the first is a single layer of inhibitory Purkinje cells which are sandwiched between a dense layer of excitatory granule cells, and another molecular layer of granular cell axons and purkinje cell dendritic fibres. The granule cells receive inputs from outside the cerebellum and project these inputs to purkinje cells where the majority of these inputs are further projected to a variety of cerebellar nuclei in the white matter . The nuclei from the cerebellum are formed by a complex process of neurogenesis and neuronal migration. There are two types of grey matter in the cerebellum, the deep cerebellar nuclei and an external cerebellar cortex. There are 4 deep nuclei formed and the output of the cerebellar cortex are relayed through these nuclei, the ventricular layer produces 4 types of neurons that migrate to the cortex. The adjacent rhombic lips gives rise to cerebellar granule cells. 
z5018156 - https://www.ncbi.nlm.nih.gov/pubmed/21295689 <ref name="PMID2775156">
Cerebellum Development Stages
Embryonic Cerebellum Development
Fetal Cerebellum Development
Developmental signalling processes
- Mechanical Movement of Neurones from Metencephalon
- Number of Divisions Determines Cell Type
- Differentiation of Specific Neurones
Dandy-Walker-Malformation (DWM) is the incomplete development of the cerebellar vermis with cystic dilatation of the 4th ventricle and enlargement of the posterior fossa (Reference: https://www.ncbi.nlm.nih.gov/pubmed/22108217). It primarily affects the development of the cerebellum. There are a variety of ways DWM may progress in which these include;
- Midline posterior fossa cyst widely communicating with the 4th ventricle
- Underdevelopment of the cerebellar vermis, which may be elevated and rotated upward
- Anterolateral displacement of normal appearing cerebellar hemispheres
- Upward displacement of the tentorium
- Enlargement of the posterior fossa
- Lack of patency of the foramina of Luschka and/or Magendie,
- Supratentorial hy- drocephalus (Reference: same article - might need to reword)
PICTURE FROM ARTICLE HERE z5018156
z5076158 could be a good article to use - https://www.ncbi.nlm.nih.gov/pubmed/22108217
- Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Neural Development.
- Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H., 2014. Larsen's Human Embryology E-Book. Elsevier Health Sciences.