Cerebellum


The cerebellum, located below the occipital lobe and posterior to the brainstem, has a large role in the modification of neural signals from the higher centers of the brain. While it houses about 50% of all the neurons in the brain, these neurons do not produce motor commands. The role of the cerebellum is more accurately described as regulating posture and balance, motor learning, coordination of movements, and some cognitive functions. [1,2,3]

Also referred to as the “little brain”, the cerebellum is divided mediolaterally and sagittally. These divisions are then organized into the cerebrocerebellum, the spinocerebellum and the vestibulocerebellum. The cerebellum may also be divided into the cerebellar cortex superficially, the deep zone and the deep cerebellar nuclei. [1,2,3]

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Figure 1




Functional Anatomy

The cerebellar cortex consists of extensive folding mediolaterally. The deep grooves and the peaks of these folds are together called the folia. The cerebellum is divided mediolaterally into the anterior lobe, the posterior lobe and the flocculonodular lobe. A deeper infolding on the superior aspect of the cerebellum referred to as the primary fissure, separates the anterior and posterior lobes. The flocculonodular lobe is located on the inferior aspect of the cerebellum, tucked between the cerebellum and the brainstem as they attach. This lobe is separated from the posterior lobe by a second deeper infolding of the folia, referred to as the posterolateral fissure. [1,2,5]

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Figure 2


The cerebellum is also divided sagittally. The most medial portion of the cerebellum is called the vermis, from the latin word for worm. The most lateral portions of the cerebellum are referred to as the lateral hemispheres, also called the lateral zones. The segments between the lateral hemispheres and the vermis are the intermediate hemispheres, or zones. [1]

These hemispheres and lobes can then be organized into subdivisions known as the cerebrocerebellum, spinocerebellum and the vestibulocerebellum, depending on the location from which they receive input, and therefore the specific functionality of the region. [1]

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Figure 3


Internal Circuitry

The outermost segment of the cerebellum is the cerebellar cortex. Within the cortex are several different kinds of cells that help regulate and modify the nature of the signal that is sent to the deep cerebellar nuclei. These cells form the grey matter that can be observed in a cross section of the cerebellum (Fig. 2) and is characteristic of the cerebellar cortex. The white matter that occupies the area below the cortex, carries the afferent fibers to the cortex, and the efferent fibers away from the cortex to the deep cerebellar nuclei, which is located in the ventral portion of the white matter. [5] This region may be referred to as the deep zone. [3]

Within the cerebellar cortex are three layers. The deepest layer is the granule cell layer, named after the granule cells, which have their cell bodies in this layer of the cortex. The most superficial layer is the molecular layer, which houses the dendrites of purkinje cells, as well as axons of granule cells that have split into parallel fibers and axons of climbing fibers. The molecular layer also contains the cell bodies of basket cells and stellate cells. The purkinje cell layer is between the molecular layer and the granule cell layer and is the location of the cell bodies if the purkinje cells. [2,8]

There are two types of fibers that carry signals to the cerebellar cortex. Mossy fibers, which originate in the spinal cord, the pontine nuclei, the vestibular nuclei and the reticular formation in the brainstem, send excitatory signals by releasing the neurotransmitter glutamate. As well as climbing fibers, which originate in the inferior olive, and send excitatory signals by releasing the neurotransmitter aspartate. [1,2,7] The mossy fibers split to form two separate loops that both end at the deep cerebellar nuclei:

Deep excitatory loop: The mossy fiber forms direct excitatory connections with the deep cerebellar nuclei.

Cortical inhibitory loop: The mossy fiber branches to synapse onto several granule cells. The granule cells are excited by the mossy fibers and project up to the molecular layer where they split and begin running transverse through this layer. When the fiber splits, the axons project in opposite directions and are called parallel fibers, because their path is now parallel to the layers of the cerebellar cortex. The parallel fibers traverse the molecular layer and synapse with the extensive dendritic branching of the purkinje cells. The purkinje cells are excited by the parallel fibers of the granule cells and project down to the deep cerebellar nuclei, where they have an inhibitory effect. [2,6,8]

The climbing fibers, once they have entered the cerebellum, will send a collateral branch to the deep cerebellar nuclei where it will have direct excitatory connections. The climbing fiber will also have an axon that will continue up to the molecular layer of the cortex, where it will branch and synapse with the dendrites of 3-10 purkinje cells. While one climbing fiber will go to several purkinje cells, a single purkinje cell will only have synapses with one climbing fiber. The climbing fiber will synapse many times on each purkinje cell it projects to. The climbing fiber will excite the purkinje cell, which will then project back down to the deep cerebellar nuclei and form inhibitory synapses. [2,6]

It is thought that the role of the inferior olive is to detect errors that occur in coordinating movements. This is possible because of the direct connections to the purkinje cells and deep cerebellar nuclei through the climbing fibers, which allows for quick inhibition or excitation of the deep cerebellar nuclei. [2] The climbing fibers are also capable of changing the response of the purkinje cells to parallel fibers, which will modify output from the cerebellum. [7]

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Figure 4


Within the cerebellar cortex there are also golgi cells, basket cells and stellate cells. The basket and stellate cells have their cell bodies in the molecular layer, whereas the golgi cells have their cell bodies in the granular layer. All of these cells receive excitatory input from collateral axons of the parallel fibers: [2]

Golgi cells: When stimulated by the parallel fibers, the golgi cells send their axons to the granule cell layer, where they inhibit the synapse between the mossy fiber and the granule cells. Through the golgi cell, the granule cell is able to inhibit the source of its own excitation, which can be referred to as feed-backward inhibition. [2,8]

Stellate cells: When stellate cells are excited by the parallel fibers of the granule cells, they send their axons to the purkinje cells, where they have inhibitory synapses. Through the stellate cells, the purkinje cells are inhibited shortly after they are excited by the parallel fibers themselves.[2]

Basket cells: The axons of basket cells projects to purkinje cells in the surround, but not to the purkinje cell that is directly adjacent to the basket cell. This means that when the basket cell is excited by the parallel fibers, it then sends an inhibitory signals to several purkinje cells in the surround, but no signal to the closest purkinje cell.[2]

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Figure 5


The deeper portion of the cerebellum is comprised of three different deep cerebellar nuclei. The most medial of these are the fastigial nuclei, and they correspond with the the purkinje cells that project from the vermis. The most lateral are the dentate nuclei, which receives information from the lateral hemispheres. The interposed nuclei are between the fastigial and dentate nuclei and therefore correspond with the intermediate hemispheres. [1,3]

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Figure 6


The circuitry in the cerebellar cortex is consistent throughout the entire cortex. The differences in function of the separate regions of the cerebellum is dependent on the varying input and output between the regions. [2]

Input & Output pathways

All input to and output from the cerebellum must travel through the peduncles, which are three bundles of fibers that sit between the brainstem and the cerebellum. The three peduncles are the inferior cerebellar peduncle (ICP), the superior cerebellar peduncle (SCP) and the middle cerebellar peduncle (MCP).

Input:

The ICP and MCP are the two peduncles primarily responsible for input to the cerebellum. The ICP is responsible for carrying input from the dorsal spinocerebellar tract (DSCT) and the cuneocerebellar tract (CCT), both of which arise in the ipsilateral spinal cord, as well as the olivocerebellar tract (OCT) and the vestibulocerebellar tract (VCT), which both arise from the contralateral brainstem. The MCP is responsible for the pontocerebellar tract (PCT) arising from the contralateral pontine nuclei. [3] Although the SCP is primarily responsible for output from the cerebellum, some information from the spinocerebellar tract enters the cerebellum via the SCP. [1]

Output:

The SCP is the primary mode of output from the cerebellum, and will carry efferent from the deep cerebellar nuclei. Though the ICP is mainly associated with afferent fibers, there is some output through this peduncle to the vestibular nuclei. [1]

It is important to note that the cerebellum corresponds with the body ipsilaterally, and therefore information must cross the midline from the cerebellum to the cerebral cortex.


Subdivisions of the cerebellum

Cerebrocerebellum:

The cerebrocerebellum is comprised of the lateral hemispheres, which mediolaterally is the lateral portions of the posterior lobe. [5] This region receives input from the contralateral cerebral cortex, which sends fibers to the pontine nuclei and into the cerebellum through the MCP. After projecting to the cerebellar cortex and through the internal circuitry, the purkinje cells from the lateral hemispheres, and therefore the cerebrocerebellum, synapse in the dentate nuclei. [5] From the dentate nucleus, fibers project through the SCP to the contralateral ventral lateral nucleus of the thalamus and then back up to the premotor and supplementary motor areas in the cerebral cortex. [2,4,5,7] From there, the information is then sent to the primary motor cortex for the initiation of the movement. Projections from the primary motor cortex travel down the corticospinal tract. [3] There will also be some projections through the SCP to the parvocellular red nucleus, which will project to the inferior olive. [7] This allows for error detection and correction, as the inferior olive will also receive input from the spinal cord and cortex. Projections from the inferior olive will enter back into the cerebellum as climbing fibers, through the ICP. In total the inferior olive will receive input about what the motor plan was and what is actually happening in the movement. The cerebrocerebellum is associated with the initiation of movements and the spatiotemporal aspect of motor planning. [6] There may also be some involvement with motor learning.

Spinocerebellum:

The vermis and the intermediate hemispheres, which are mediolaterally formed by the entire anterior lobe and the medial aspect of the posterior lobe, together comprise the spinocerebellum. [5] This subdivision of the cerebellum has somatotopic mapping, in which different areas of the spinocerebellum represent different regions of the body. The map that lies more anterior in the spinocerebellum and is in both the vermis and intermediate hemispheres mimics an individual lying on their back with the extremities spread out to the sides and is inverted. The map that is located posteriorly in the intermediate hemispheres is an upright mirror-image. [4] The anterior vermis represents axial and proximal limb coordination, and the intermediate hemispheres represent distal limb coordination. Information from the spinal cord ascend on fibers in the DSCT and the CCT and enter the cerebellum through the ICP. Interneurons also travel up the VSCT and RSCT and enter the spinocerebellum through the SCP. There are two separate pathways through the spinocerebellum due to the two sagittal divisions that comprise this subdivision of the cerebellum. [2]

The purkinje fibers from the vermis project to the fastigial nuclei. [5] From the fastigial nuclei, the fibers then project out of the cerebellum through the SCP to the tectum in the superior colliculus, taking part in stimulating the tectospinal pathway, as well as projecting to the VL of the thalamus and then affecting the medial CST through the cortex. There will also be projections through the ICP that will travel to the reticular formation in the brainstem, affecting the pontine and medullary reticulospinal tracts, and to the vestibular nuclei to stimulate primarily the vestibulospinal tracts. [2]

The purkinje fibers from the intermediate hemispheres connect to the interposed nuclei [5], which then project out of the cerebellum through the SCP to the magnocellular red nucleus. From the red nucleus, this projections down the spinal cord on the rubrospinal tract allow the cerebellum to affect flexor muscles in the limbs. [2] There are also projections from the intermediathe hemispheres back to the VL of the thalamus, which then influence the lateral CST through the cortex.

In addition to sensory input, this are also receives information about the motor plan. The motor cortex project to the pontine nuclei, which has projections that cross the midline and travel to the intermediate hemisphere. The cortex also has projections that travel to the brainstem, where it decussates and then descends to the aplha-motor neuron. There is also a collateral axon that synapses with an interneuron. The interneuron decussates and ascends on the ventral spinocerebellar tract and enters the cerebellum through the SCP and travels to the intermediate hemisphere. The spinocerebellum is associated with the ability to adapt, modify and control the execution of movements, as well as sensory-motor integration. [1,6]


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Figure 7


Vestibulocerebellum:

The flocculonodular lobe forms the subdivision known as the vestibulocerebellum. This region receives input from the vestibular nuclei, as well as the vestibular nerve, which enters the cerebellum through the ICP. The purkinje fibers from the vestibulocerebellum do not project to the deep cerebellar nuclei, but to the vestibular nuclei [5,7], which in this case are referred to as the surrogate nuclei. The purkinje fibers project out of the cerebellum through the ICP. Through the connections to the vestibular nuclei, the vestibulocerebellum will affect the vestibular ocular reflex (VOR) and the medial and lateral vestibulospinal tracts. This subdivision also allows the vestibular system to compensate when there is damage to the system. [2] The main role of the vestibulocerebellum is the control of body equilibrium and eye movements. [6]



Conclusion

The functionality of the cerebellum can best be described throught the subdivisions known as the spinocerebellum, cerebrocerebellum and the vestibulocerebellum. The spinocerebellum's primary role is to provide a form of online adaption that aids in the execution of the movement. The cerebrocerebellum is primarily involved in timing aspect of motor planning, and in this way is involved in the initiation of the movement. The vestibulocerebellum is mainly involved in controlling eye movements through the VOR, and maintaining body equilibrium. Information sent to the cerebellum will enter in form of signals from either a mossy fiber or a climbing fiber. Both types of fibers will form two separate loops, one involving direct excitation of the deep cerebellar nuclei, and the involving synapses in the cortex and projecting inhibitory signals back to the deep cerebellar nuclei through the purkinje cells. Despite the complexity of this, the internal circuitry is fairly consistent throughout the cerebellum, and therefore functional differences between the subdivisions are the result of varying input to and output from the separate regions.


Glossary of terms

Dorsal spinocerebellar tract - The tract that is associated with carrying proprioception information to the cerebellum from the lower truck and lower extremities (T1 and below).

Cuneocerebellar tract - The tract associated with carrying proprioceptive information to the cerebellum from the upper extremities and truck (C8 and above).

Reticular formation - In the case of the cerebellum, this region can be largely associated with the reticulospinal descending pathways. The pontine reticulospinal tract is associated largely with axial tone, while the meduallary reticulospinal tract is associated with counteracting tone in distal musculature.

Red nucleus - In terms of the cerebellum, the magnocellular red nucleus is associated with the descending rubrospinal tract, which influences upper extremity flexors, and the parvocellular red nucleus, which relays information to the inferior olive.

Vestibular ocular reflex - Stimulation of the canals in the vestibular apparatus causes excitation of the medial and superior vestibular nuclei. These nuclei excite the contralateral abducens and therefore the contralateral lateral rectus, and the ipsilateral oculomotor nucleus and therefore the ipsilateral medial rectus. This allows the eyes to continue foveating on an object as the head turns. This mechanism can be influenced by the cerebellum and cause the eyes to track an object in smooth pursuit, while the head stays still.

Vestibular nuclei - Located in the brainstem, receives input from the canals and the otolithic organs in the vestibular system, as well as from the cerebellum. Two pathways descend from this regions, controlling the collic reflex and the extensor reflex that are both primarily associated with sudden stimulation of the vestibular apparatus. This area is the primary control of the VOR through connection to the abducens nuclei, and also sends projections to the cerebellum. The cerebellum is able to aid in coordination of eye movements through this region of the brainstem.

Pontine nuclei - Located in the brainstem, is the main way in which input from the cortex enters the cerebellum

Thalamus - Located between the midbrain and the cerebral cortex, information from the cerebellum is relayed through this region to the cortex.

Premotor area - A part of the premotor cortex that is involved in planning movements. This area is the get ready signal and is even active into the performance of the movement.

Supplementary motor areas - A part of the premotor cortex that can be associated with planning a movement. This specific area of the premotor cortex is associated with planning the sequencing of movements.

Alpha-motor neuron - A type of neuron that projects it axon to a muscle and forms a neuromuscular junction in which neurotransmiters will be sent out of the terminal ending of the axon and synapse with the receptors on the sarcolemma of the muscle and cause excitation of the muscle.


Relevant links

The following link provides information on the causes and manifestations of cerebellar disorders - http://www.uzhelth.org/docs/second-student-mobility/Disorders%20of%20the%20Cerebellum%20Fredericks%201996.pdf

A review in which Susanne M. Morton and Amy J. Bastion look at studies involving both humans and other animals in order to observe the cerebellum's role in balance and locomotion - http://journals.sagepub.com/doi/abs/10.1177/1073858404263517

In this video overview, additional information about the cerebellum is provided by Claudia Krebs at the University of British Columbia - http://www.neuroanatomy.ca/video_list.html?id=3

An article by Jan Voogd and Mitchell Glickstein that provides additional information on the functional anatomy of the cerebellum - http://www.neurosci.info/courses/systems/Cerebellum/Voogd.pdf


Quiz

True/False
  1. The internal circuitry of the cerebellum varies greatly between the cerebrocerebellum, spinocerebellum and vestibulocerebellum and are therefore the cause of the functional differences between these subdivisions.
  2. Climbing fibers originate strictly from the inferior olive, while mossy fibers originate form the various other areas that project to the cerebellum.
  3. The superior cerebellar peduncle is the primary mode of input to the cerebellum and has very little role in output from the cerebellum.
  4. Projections from the vermis through the thalamus and to the cortex will affect the lateral corticospinal tract.

Multiple Choice

1. The anterior and posterior lobes of the cerebellum are separated by which landmark:
a. posterolateral fissure
b. central sulcus
c. primary fissure
d. lateral fissure

2. The molecular layer of the cerebellar cortex houses the cell bodies of which of the following cells:
a. golgi cells
b. stellate cells
c. basket cells
d. A & B
e. B & C

3. Mossy Fibers will form two separate loops as part of the internal circuitry of the cerebellum. The name of the loop that involves a direct synapse between the mossy fiber and the deep cerebellar nucleus is referred to as:
a. deep excitatory loop
b. deep inhibitory loop
c. cortical inhibitory loop
d. cortical excitatory loop

4. The spinocerebellum is comprised of which of the following region(s):
a. Vermis
b. Intermediate hemispheres
c. Lateral hemispheres
d. Flocculonodular lobe
e. A & B
f. A & C

Short Answer
  1. Which sagittal division of the cerebellum is associated with axial musculature in reference to the somatotopic mapping?
  2. Name the three deep cerebellar nuclei and the sagittal divisions that are associated with.
  3. The vestibulocerebellum does not have connections to the deep cerebellar nuclei. Instead, purkinje cells project out of the cerebellum to what region?

Essay
  1. Provide a description of the function of each of the subdivisions of the cerebellum.
  2. Describe the internal circuitry of the cerebellum including; all different cells involved, where they synapse, and whether the synapse is excitatory or inhibitory.


References

Text
  1. Knierim, J. (1997). Cerebellum (Section 3, Chapter 5) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. Retrieved December 20, 2016, from http://nba.uth.tmc.edu/neuroscience/m/s3/chapter05.html
  2. Swenson, R. (2006). Chapter 8B - Cerebellar Systems. Retrieved December 20, 2016, from
    https://www.dartmouth.edu/~rswenson/NeuroSci/chapter_8B.html
  3. Harting , J. K. (1997, February 1). The Cerebellum - Contents. Retrieved November 26, 2016, from http://www.neuroanatomy.wisc.edu/cere/text/cere/contents.htm
  4. Buckner, R. L., Krienen, F. M., Castellanos, A., Diaz, J. C., & Yeo, B. T. T. (2011). The organization of the human cerebellum estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(5), 2322–2345. http://doi.org/10.1152/jn.00339.2011
  5. Elizabeth, O., & Molliver, M. E. (2001). Organizational principles and microcircuitry of the cerebellum. International Review of Psychiatry,13(4), 232-246. doi:10.1080/09540260120082083
  6. Salman, M. S. (2002). Topical Review : The Cerebellum: It's About Time! But Timing Is Not Everything-New Insights Into the Role of the Cerebellum in Timing Motor and Cognitive Tasks. Journal of Child Neurology, 17(1), 1-9. doi:10.1177/088307380201700101
  7. Morton, S. M., & Bastian, A. J. (2016). Cerebellar Control of Balance and Locomotion. The Neuroscientist, 10(3), 247-259. Retrieved December 19, 2016, from http://journals.sagepub.com/doi/abs/10.1177/1073858404263517
  8. Voogd J, Glickstein M. (1998). The anatomy of the cerebellum. Trends Neurosci 21:370–5. Retrieved December 19, 2016, from http://www.neurosci.info/courses/systems/Cerebellum/Voogd.pdf

Images
  1. http://www.memorylossonline.com/glossary/cerebellum.html
  2. http://what-when-how.com/neuroscience/brainstem-ii-pons-and-cerebellum-part-2/
  3. https://www.slideshare.net/mobile/drchintansinh/cerebellum-61499736
  4. https://kin450-neurophysiology.wikispaces.com/Cerebellum
  5. http://aibolita.com/nervous-diseases/47904-cerebellar-cortex.html
  6. http://humanphysiology.academy/Neurosciences%202015/BS%20Tutorials/T.5%20Basal%20Ganglia%20and%20Cerebellum.html
  7. http://slideplayer.com/slide/7815798/


Quiz answers:
True/false
  1. F
  2. T
  3. F
  4. F
Multiple choice
  1. C
  2. E
  3. A
  4. E
Short answer
  1. Vermis
  2. Fastigial -Vermis, Interposed - intermediate hemispheres, Dentate - Lateral hemispheres
  3. Vestibular nuclei