Cerebellum
50397
224518643
2008-07-09T05:50:20Z
61.78.116.117
/* Phylogenetic and functional divisions */
{{Infobox Brain|
Name = Cerebellum |
Latin = |
GraySubject = |
GrayPage = |
Image = Cerebellum_NIH.png |
Caption = Figure 1a: A [[human brain]], with the cerebellum in purple. |
Image2 = Cerebellum_sag.jpg |
Caption2 = Figure 1b: [[Magnetic resonance imaging|MRI]] image showing a mid-[[sagittal]] view of the human brain, with the cerebellum in purple. |
IsPartOf = [[Brain]]|
Components = |
Artery = [[Superior cerebellar artery|SCA]], [[anterior inferior cerebellar artery|AICA]], [[posterior inferior cerebellar artery|PICA]] |
Vein = [[superior cerebellar veins|superior]], [[inferior cerebellar veins|inferior]] |
BrainInfoType = |
BrainInfoNumber = |
MeshNumber = A08.186.211.132.810.428.200 |
DorlandsSuf = |
}}
{{portalpar|Neuroscience|Neuro logo.png}}
The '''cerebellum''' is a region of the [[brain]] that plays an important role in the integration of [[perception|sensory perception]], coordination and [[motoneuron|motor]] control. In order to coordinate motor control, there are many [[neural pathway]]s linking the cerebellum with the [[cerebrum|cerebral]] [[motor cortex]] (which sends information to the [[muscle]]s causing them to move) and the [[spinocerebellar tract]] (which provides [[proprioception|proprioceptive]] feedback on the position of the body in space). The cerebellum integrates these pathways, like a train conductor, using the constant feedback on body position to fine-tune motor movements.<ref name="Fine">{{cite journal | author=Fine EJ, Ionita CC, Lohr L | title=The history of the development of the cerebellar examination | journal=Semin Neurol | year=2002 | pages=375–84 | volume=22 | issue=4 | pmid=12539058 | doi = 10.1055/s-2002-36759 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
Because of this 'updating' function of the cerebellum, [[lesion]]s within it are not so debilitating as to cause [[paralysis]], but rather present as [[feedback]] deficits resulting in disorders in fine movement, [[Equilibrioception|equilibrium]], [[Human position|posture]], and [[motor learning]]. Initial observations by [[physiology|physiologists]] during the 18th century indicated that patients with cerebellar damage show problems with [[motor coordination]] and movement. Research into cerebellar function during the early to mid 19th century was done via lesion and ablation studies in [[animal]]s. Research physiologists noted that such lesions led to animals with strange movements, awkward gait, and muscular weakness. These observations and studies led to the conclusion that the cerebellum was a motor control structure.<ref name="Fine"/> However, modern research shows that the cerebellum has a broader role in a number of key cognitive functions, including [[attention]] and the processing of [[language]], [[music]], and other sensory temporal stimuli.<ref>{{cite book |last=Rapp |first=Brenda |title=The Handbook of Cognitive Neuropsychology: What Deficits Reveal about the Human Mind |year=2001 |publisher=Psychology Press |isbn=1841690449 |pages=481 }}</ref>
==General features==
The cerebellum is located in the inferior posterior portion of the head (the [[rhombencephalon|hindbrain]]), directly dorsal to the [[pons]], and inferior to the [[occipital lobe]] (Figs. 1 and 3). Because of its large number of tiny [[granule cell]]s, the cerebellum contains more than 50% of all [[neuron]]s in the brain, but it only takes up 10% of total brain volume.<ref>[http://thebrain.mcgill.ca/flash/d/d_06/d_06_cr/d_06_cr_mou/d_06_cr_mou.html The Brain From Top To Bottom<!-- Bot generated title -->]</ref> The cerebellum receives nearly 200 million input fibers; in contrast, the [[optic nerve]] is composed of a mere one million fibers.
The cerebellum is divided into two large [[Sphere|hemisphere]]s, much like the [[telencephalon|cerebrum]], and contains ten smaller lobules. The [[cytoarchitectonics|cytoarchitecture]] ([[cell (biology)|cellular]] organization) of the cerebellum is highly uniform, with connections organized into a rough, [[dimension|three-dimensional]] [[array]] of perpendicular [[biological neural network|circuit]] elements. This organizational uniformity makes the nerve circuitry relatively easy to study. To envision this "perpendicular array," one might imagine a tree-lined street with wires running straight through the branches of one tree to the next.{{Clarifyme|date=March 2008}}
==Development and evolution==
[[Image:CajalCerebellum.jpg|right|thumb|300px|Figure 2: Drawing of the [[cell (biology)|cells]] in the [[chicken]] cerebellum by [[Santiago Ramón y Cajal|S. Ramón y Cajal]].]]
During the early stages of [[embryogenesis|embryonic development]], the brain starts to form in three distinct segments: the [[prosencephalon]], [[mesencephalon]], and [[rhombencephalon]]. The rhombencephalon is the most caudal (toward the tail) segment of the embryonic brain; it is from this segment that the cerebellum develops. Along the embryonic rhombencephalic segment develop eight swellings, called [[rhombomere]]s. The cerebellum arises from two rhombomeres located in the [[alar plate]] of the [[neural tube]], a structure that eventually forms the brain and spinal cord. The specific rhombomeres from which the cerebellum forms are rhombomere 1 (Rh.1) caudally (near the tail) and the "isthmus" rostrally (near the front).<!--
--><ref name="Muller">{{cite journal | author=Muller F, O'Rahilly R | title=The human brain at stages 21–23, with particular reference to the cerebral cortical plate and to the development of the cerebellum | journal=Anat Embryol (Berl) | year=1990 | pages=375–400 | volume=182 | issue=4 | pmid=2252222 | doi=10.1007/BF02433497}}</ref>
Two primary regions are thought to give rise to the neurons that make up the cerebellum. The first region is the ventricular zone in the roof of the [[fourth ventricle]]. This area produces [[Purkinje cell]]s and deep cerebellar [[nucleus (neuroanatomy)|nuclear]] neurons. These cells are the primary output neurons of the cerebellar cortex and cerebellum. The second germinal zone (cellular birthplace) is known as the Rhombic lip, neurons then move by embryonic week 27 to the external granular layer. This layer of cells—found on the exterior the cerebellum—produces the granule neurons. The granule neurons migrate from this exterior layer to form an inner layer known as the internal granule layer. The external granular layer ceases to exist in the mature cerebellum, leaving only granule cells in the internal granule layer. The cerebellar [[white matter]] may be a third germinal zone in the cerebellum; however, its function as a germinal zone is controversial.
The cerebellum is of [[archipallium|archipalliar]] [[phylogeny|phylogenetic]] origin. The [[pallium (anatomy)|pallium]] is a term for gray matter that forms the cortex. The archipallium is one of the most [[evolution]]arily primitive brain regions. The circuits in the cerebellar cortex look similar across all [[class (biology)|class]]es of [[vertebrate]]s, including [[fish]], [[reptiles]], [[birds]], and [[mammals]] (e.g., Fig. 2). This has been taken as evidence that the cerebellum performs functions important to all vertebrate [[species]].
==Anatomy==
The cerebellum contains similar [[gray matter|gray]] and white matter divisions as the [[cerebrum]]. Embedded within the white matter—which is known as the ''[[arbor vitae (anatomy)|arbor vitae]]'' (Tree of Life) in the cerebellum due to its branched, [[tree]]like appearance—are four deep cerebellar nuclei. Three gross phylogenetic segments are largely grouped by general function. The three cortical layers contain various cellular types that often create various feedback and feedforward loops. [[Oxygen]]ated [[blood]] is supplied by three [[artery|arterial]] branches off the [[basilar artery|basilar]] and [[vertebral artery|vertebral arteries]].
===Divisions===
The cerebellum can be divided according to three different criteria: gross anatomical, phyologenetical, and functional.
====Gross anatomical divisions====
On gross inspection, three lobes can be distinguished in the cerebellum: the '''flocculonodular lobe''', the '''anterior lobe''' (rostral to the "primary fissure"), and the '''posterior lobe''' (dorsal to the "primary fissure"). The latter two can be further divided in a midline '''[[cerebellar vermis]]''' and lateral '''cerebellar hemispheres'''.
{| align=center
| [[Image:CerebellumRegions.jpg|thumb|center|400px|Figure 3: Cerebellum and surrounding regions; sagittal view of one hemisphere. A: [[Midbrain]]. B: [[Pons]]. C: [[Medulla oblongata|Medulla]]. D: [[Spinal cord]]. E: [[ventricular system|Fourth ventricle]]. F: [[Arbor vitae (anatomy)|''Arbor vitae'']]. G: [[Cerebellar tonsils|Tonsil]]. H: Anterior lobe. I: Posterior lobe.]] || [[Image:CerebellumDiv.png|thumb|center|380px|Figure 4: Schematic representation of the major anatomical subdivisions of the cerebellum. Superior view of an "unrolled" cerebellum, placing the vermis in one plane.]]
|}
====Phylogenetic and functional divisions====
The cerebellum can also be divided in three parts based on both [[phylogenetics|phylogenetic]] criteria (the evolutionary age of each part) and on functional criteria (the incoming and outgoing connections each part has and the role played in normal cerebellar function). From the phylogenetically oldest to the newest, the three parts are:
{| class="wikitable"
| '''Functional denomination''' (''phylogenetic denomination)'' || '''Anatomical parts''' || '''Role'''
|-
| '''Vestibulocerebellum''' ''(Archicerebellum)'' || [[Flocculonodular lobe]] (and immediately adjacent vermis) || The vestibulocerebellum regulates balance and eye movements. It receives [[vestibular system|vestibular]] input from both the [[semicircular canals]] and from the [[vestibular nuclei]], and sends fibres back to the medial and lateral vestibular nuclei. It also receives [[visual system|visual]] input from the [[superior colliculi]] and from the [[visual cortex]] (the latter via the [[pontine nuclei]], forming a cortico-ponto-cerebellar pathway). Lesions of the vestibulocerebellum cause disturbances of balance and [[gait]].
|-
| '''Spinocerebellum''' ''(Paleocerebellum)'' || [[Vermis]] and intermediate parts of the hemispheres ("paravermis") || The spinocerebellum regulates body and limb movements. It receives [[proprioceptive|proprioception]] input from the dorsal columns of the [[spinal cord]] (including the [[spinocerebellar tract]]) as well as from the [[trigeminal nerve]], as well as from visual and [[auditory system|auditory]] systems. It sends fibres to deep cerebellar nuclei which in turn project to both the cerebral cortex and the brain stem, thus providing modulation of descending motor systems. The spinocerebellum contains sensory maps as it receives data on the position of various body parts in space: in particular, the vermis receives fibres from the trunk and proximal portions of limbs, while the intermediate parts of the hemispheres receive fibres from the distal portions of limbs. The spinocerebellum is able to elaborate proprioceptive input in order to anticipate the future position of a body part during the course of a movement, in a "feed forward" manner.
|-
| '''Cerebrocerebellum''' ''(Neocerebellum, Pontocerebellum)'' || Lateral parts of the [[Cerebellar hemisphere|hemisphere]]s || The neocerebellum is involved in planning movement and evaluating sensory information for action. It receives input exclusively from the cerebral cortex (especially the [[parietal lobe]]) via the pontine nuclei (forming cortico-ponto-cerebellar pathways), and sends fibres mainly to the ventrolateral [[thalamus]] (in turn connected to motor areas of the [[premotor cortex]] and [[primary motor area]] of the cerebral cortex) and to the [[red nucleus]] (in turn connected to the [[inferior olivary nucleus]], which links back to the cerebellar hemispheres). The neocerebellum is involved in planning movement that is about to occur<ref>{{cite book|last=Kingsley |first=R. E.|authorlink=|title=Concise Text of Neuroscience|edition=2nd edition|publisher=Lippincott Williams and Wilkins|location=|year=2000|isbn=0-683-30460-7|series=}}</ref> and has purely cognitive functions as well.
|}
Much of what is understood about the functions of the cerebellum stems from careful documentation of the effects of focal lesions in human patients who have suffered from injury or disease or through animal lesion research.
===Deep nuclei===
{{Main|Deep cerebellar nuclei}}
The deep nuclei of the cerebellum act as the main centers of communication, and the four different nuclei of the cerebellum (dentate, interpositus, fastigial, and vestibular) receive and send information to specific parts of the brain. In addition, these nuclei receive both inhibitory and excitatory signals from other parts of the brain which in turn affect the nucleus's outgoing signals.<ref>John K. Harting, Ph.D. The Global Cerebellum '97,[http://www.neuroanatomy.wisc.edu/cere/text/P5/intro.htm] University of Wisconsin Medical School.</ref>
===Cortical layers===
[[Image:CerebCircuit.png|thumb|300px|right|Figure 5: Microcircuitry of the cerebellum. Excitatory synapses are denoted by (+) and inhibitory synapses by (-). MF: [[Mossy fiber (cerebellum)| Mossy fiber]]. DCN: Deep cerebellar nuclei. IO: [[Inferior olivary nucleus|Inferior olive]]. CF: [[Climbing fiber]]. GC: Granule cell. PF: [[Parallel fiber]]. PC: [[Purkinje cell]]. GgC: Golgi cell. SC: Stellate cell. BC: Basket cell.]]
[[Image:L7cerebellum.png|thumb|300px|right|Figure 6: [[Confocal laser scanning microscopy|Confocal]] [[micrograph]] from [[mouse]] cerebellum expressing green-fluorescent protein in [[Purkinje cells]].]]
There are three layers to the cerebellar cortex; from outer to inner layer, these are the molecular, Purkinje, and granular layers. The function of the cerebellar cortex is essentially to modulate information flowing through the deep nuclei. The microcircuitry of the cerebellum is schematized in Figure 5. [[Mossy fiber (cerebellum)|Mossy]] and [[climbing fiber]]s carry sensorimotor information into the deep nuclei, which in turn pass it on to various premotor areas, thus regulating the [[Gain#Electronics|gain]] and timing of motor actions. Mossy and climbing fibers also feed this information into the cerebellar cortex, which performs various computations, resulting in the regulation of Purkinje cell firing. Purkinje neurons feed back into the deep nuclei via a potent inhibitory [[synapse]]. This synapse regulates the extent to which mossy and climbing fibers activate the deep nuclei, and thus control the ultimate effect of the cerebellum on motor function. The synaptic strength of almost every synapse in the cerebellar cortex has been shown to undergo [[synaptic plasticity]]. This allows the circuitry of the cerebellar cortex to continuously adjust and fine-tune the output of the cerebellum, forming the basis of some types of motor learning and coordination. Each layer in the cerebellar cortex contains the various cell types that comprise this circuitry.
====Granular layer====
The innermost layer contains the cell bodies of two types of cells: the numerous and tiny [[granule cell]]s, and the larger [[Golgi cell]]s. Mossy fibers enter the granular layer from their main point of origin, the pontine nuclei. These fibers form excitatory synapses with the granule cells and the cells of the deep cerebellar nuclei. The granule cells send their T-shaped axons—known as [[parallel fiber]]s—up into the superficial molecular layer, where they form hundreds of thousands of synapses with Purkinje cell [[dendrite]]s. The human cerebellum contains on the order of 60 to 80 billion granule cells, making this single cell type by far the most numerous neuron in the brain (roughly 70% of all neurons in the brain and spinal cord, combined). Golgi cells provide inhibitory feedback to granule cells, forming a synapse with them and projecting an axon into the molecular layer.
====Purkinje layer====
The middle layer contains only one type of cell body—that of the large [[Purkinje cell]]. Purkinje cells are the primary integrative neurons of the cerebellar cortex and provide its sole output. Purkinje cell dendrites are large arbors with hundreds of spiny branches reaching up into the molecular layer (Fig. 6). These dendritic arbors are flat—nearly all of them lie in planes—with neighboring Purkinje arbors in parallel planes. Each parallel fiber from the granule cells runs [[orthogonality|orthogonally]] through these arbors, like a wire passing through many layers. Purkinje neurons are GABAergic—meaning they have inhibitory synapses—with the neurons of the deep cerebellar and vestibular nuclei in the brainstem. Each Purkinje cell receives excitatory input from 100,000 to 200,000 parallel fibers. Parallel fibers are said to be responsible for the simple (all or nothing, [[amplitude]] invariant) spiking of the Purkinje cell.
Purkinje cells also receive input from the [[inferior olivary nucleus]] via [[climbing fiber]]s. A good mnemonic for this interaction is the phrase "climb the other olive tree", given that climbing fibers originate from the contralateral inferior olive. In striking contrast to the 100,000-plus inputs from parallel fibers, each Purkinje cell receives input from exactly one climbing fiber; but this single fiber "climbs" the dendrites of the Purkinje cell, winding around them and making a large number of synapses as it goes. The net input is so strong that a single [[action potential]] from a climbing fiber is capable of producing a "complex spike" in the Purkinje cell: a burst of several spikes in a row, with diminishing amplitude, followed by a pause during which simple spikes are suppressed.
====Molecular layer====
This outermost layer of the cerebellar cortex contains two types of inhibitory [[interneuron]]s: the [[stellate cell|stellate]] and [[basket cell]]s. It also contains the dendritic arbors of Purkinje neurons and parallel fiber tracts from the granule cells. Both stellate and basket cells form GABAergic synapses onto Purkinje cell dendrites.
===Peduncles===
Similarly, the cerebellum follows the trend of "threes", with three major input and output peduncles (fiber bundles). These are the superior (brachium conjunctivum), middle (brachium pontis), and inferior (restiform body) cerebellar peduncles.
{| class="wikitable"
| '''Peduncle''' || '''Description'''
|-
| [[Superior cerebellar peduncles|Superior]] || While there are some afferent fibers from the [[anterior spinocerebellar tract]] that are conveyed to the anterior cerebellar lobe via this peduncle, most of the fibers are efferents. Thus, the superior cerebellar peduncle is the major output pathway of the cerebellum. Most of the efferent fibers originate within the [[dentate nucleus]] which in turn project to various [[midbrain]] structures including the [[red nucleus]], the ventral lateral/ventral anterior nucleus of the [[thalamus]], and the [[medulla]]. The [[dentatorubrothalamocortical]] (dentate nucleus > [[red nucleus]] > [[thalamus]] > [[premotor cortex]]) and [[cerebellothalamocortical]] (cerebellum > thalamus > premotor cortex) pathways are two major pathways that pass through this peduncle and are important in motor planning.
|-
| [[Middle cerebellar peduncles|Middle]] || This is composed entirely of afferent fibers originating within the [[pontine nuclei]] as part of the massive [[corticopontocerebellar tract]] (cerebral cortex > pons > cerebellum). These fibers descend from the sensory and motor areas of the cerebral [[neopallium|neocortex]] and make the middle cerebellar peduncle the largest of the three cerebellar peduncles.
|-
| [[Inferior cerebellar peduncle|Inferior]] || This carries many types of input and output fibers that are mainly concerned with integrating [[Proprioception|proprioceptive]] sensory input with motor [[Vestibular system|vestibular functions]] such as balance and posture maintenance. Proprioceptive information from the body is carried to the cerebellum via the dorsal [[spinocerebellar tract]]. This tract passes through the inferior cerebellar peduncle and synapses within the paleocerebellum. Vestibular information projects onto the archicerebellum.<BR>The [[climbing fiber]]s of the [[Inferior olivary nucleus|inferior olive]] run through the inferior cerebellar peduncle.<BR>This peduncle also carries information directly from the [[Purkinje cells]] out to the [[vestibular nuclei]] in the dorsal brainstem located at the junction between the [[pons]] and [[medulla]].
|}
There are three sources of input to the cerebellum, in two categories consisting of mossy and climbing fibers, respectively. Mossy fibers can originate from the pontine nuclei, which are clusters of neurons located in the pons that carry information from the contralateral cerebral cortex. They may also arise within the spinocerebellar tract whose origin is located in the [[Anatomical position|ipsilateral]] [[spinal cord]]. Most of the output from the cerebellum initially synapses onto the deep cerebellar nuclei before exiting via the three peduncles. The most notable exception is the direct inhibition of the vestibular nuclei by Purkinje cells.
===Blood supply===
[[Image:CerebellumArteries.jpg|right|thumb|300px|Figure 7: The three major arteries of the cerebellum: the SCA, AICA, and PICA.]]
Three arteries supply blood to the cerebellum (Fig. 7): the [[superior cerebellar artery]] (SCA), [[anterior inferior cerebellar artery]] (AICA), and [[posterior inferior cerebellar artery]] (PICA).
====Superior cerebellar artery====
The SCA branches off the lateral portion of the basilar artery, just inferior to its bifurcation into the posterior cerebral artery. Here it wraps posteriorly around the pons (to which it also supplies blood) before reaching the cerebellum. The SCA supplies blood to most of the cerebellar cortex, the cerebellar nuclei, and the middle and superior cerebellar peduncles.
====Anterior inferior cerebellar artery====
The AICA branches off the lateral portion of the basilar artery, just superior to the junction of the vertebral arteries. From its origin, it branches along the inferior portion of the pons at the cerebellopontine angle before reaching the cerebellum. This artery supplies blood to the anterior portion of the inferior cerebellum, and to the [[facial nerve|facial]] (CN VII) and [[vestibulocochlear nerve]]s (CN VIII).
Obstruction of the AICA can cause [[paresis]], [[paralysis]], and loss of sensation in the face; it can also cause [[hearing impairment]]. Moreover, it could cause an infarct of the cerebellopontine angle. This could lead to [[hyperacusia]] (dysfunction of the stapedius muscle, innervated by [[CN VII]]) and [[vertigo (medical)|vertigo]] (wrong interpretation from the vestibular semi-circular canal's [[endolymph]] acceleration caused by alteration of [[CN VIII]]).
====Posterior inferior cerebellar artery====
The PICA branches off the lateral portion of the vertebral arteries just inferior to their junction with the basilar artery. Before reaching the inferior surface of the cerebellum, the PICA sends branches into the medulla, supplying blood to several [[cranial nerve]] nuclei. In the cerebellum, the PICA supplies blood to the posterior inferior portion of the cerebellum, the inferior cerebellar peduncle, the [[nucleus ambiguus]], the [[vagus nerve|vagus]] motor nucleus, the spinal [[trigeminal nerve|trigeminal]] nucleus, the [[solitary nucleus]], and the [[vestibulocochlear nerve|vestibulocochlear]] nuclei.
==General Function==
Functionally, the [[climbing fiber]] and the [[mossy fiber]]-granule cell-parallel fiber pathways are the two main types of afferents to the cerebellum as a whole and to the Purkinje cells in particular. <ref> Ramon y Cajal. R. (1904). "La Textura del Sistema Nervioso del Hombre y los Vertebrados". Madrid: Moya.</ref><ref> Eccles J.C Ito, M and Szentagothai J. (1967). "The cerebellum as a neuronal machine". Springer Verlag </ref> These afferent systems differ dramatically in their connectivity. The Purkinje cell and its climbing fiber afferent have a one-to-one relationship and the overall projection is organized to produce synchronous activation of specific groupings of Purkinje cells in a rostrocaudal orientation. The relationship between the Purkinje cell and the mossy fiber-parallel fiber system can be characterized as many-to-many. With the directionality being mediolateral orientation within the molecular layer i.e. at right angles to the Purkinje cell dendrites which are isoplanar .
'''The climbing fiber system'''
Originates from the contralateral inferior olive. As a result of the electrical coupling between inferior olivary neurons, their dynamic decoupling via return inhibition from the cerebellar nuclei<ref> Llinás, R., Baker, R. and Sotelo, C. (1974). "Electrotonic coupling between neurons in cat inferior olive". J. Neurophysiol 37: 560-571.</ref> and the topography of the olivocerebellar projection, this system generates synchronous (on a millisecond time scale) complex spike activation of Purkinje cells, in rostrocaudally oriented bands. These activity bands are about 250 µm wide in the mediolateral direction but can be several millimeters long in the rostrocaudal direction and extend down the walls of the cerebellar folia and across several lobules.<ref>Sugihara, I., Lang, E.J. and Llinás, R. (1993). "Uniform olivocerebellar conduction time underlies Purkinje cell complex spike synchronicity in the rat cerebellum". J. Physiol. Lond. 470: 243-271.</ref> The moment–to–moment synchrony distribution of motor control is dynamically modulated by the inferior olive with the major role of the olivary afferents being to determine the pattern of "effective" electronic coupling between olivary neurons and thereby the distribution of synchronous complex spike activity across the cerebellar cortex. Changes in synchrony patterns are associated with movements made by animals performing a motor task.<ref> Welsh, J.P., Lang, E.J., Sugihara, I. and Llinás, R. (1995). "Dynamic organization of motor control within the olivocerebellar system". Nature 374: 453-457</ref>.<ref> Lang, E.J. (2001). "Organization of olivocerebellar activity in the absence of excitatory glutamatergic input". J. Neurosci. 21: 1663-1675 </ref> Indeed. The olivocerebellar system can be considered an electrically malleable substrate from which unique motor synergies can be sculpted.
'''The Mossy Fiber-Parallel fiber system'''
In contrast to the punctate nature of cerebellar activation by the olivocerebellar system, the mossy fiber-parallel fiber system provides a continuous and very delicate regulation of the excitability of the [[cerebellar nuclei]], brought about by the tonic activation of simple spikes in Purkinje cells, which ultimately generates the fine control of movement known as motor coordination. The fact that the mossy fibers inform the cerebellar cortex of both ascending and descending messages to and from the motor centers in the spinal cord and brainstem gives us an idea of the ultimate role of the mossy fiber system: it informs the cortex of the place and rate of movement of limbs and puts the motor intentions generated by the brain into the context of the status of the body at the time the movement is to be executed. Moreover, through its effects on the inhibitory GABAergic cerebellar nuclear cells, which project back to the inferior olive, it helps shape the pattern of coupling among olivary cells and hence the synchrony distribution in the upcoming olivocerebellar discharge.
'''The cerebellar Nuclei'''
The Purkinje cells are the only output of the cerebellar cortex and are inhibitory in nature<ref> Ito, M., Yoshida, M. and Obata, K. (1964). "Monosynaptic inhibition of the intracerebellar nuclei induced from the cerebellar cortex". Experientia 20: 575-576.</ref> Their axons contact the cerebellar and Deiters vestibular nucleus as their only target. The activity of the cerebellar nuclei is regulated in three ways: (1) by excitatory input from collaterals of the cerebellar afferent systems, (2) by inhibitory inputs from Purkinje cells activated over the mossy fiber pathways, and (3) by inputs from Purkinje cells activated by the climbing fiber system
'''Overall Cerebellar Function'''
The output of the cerebellum (the cerebellar nuclei axons) proceed to generate the background activity that serves to set the overall tone and posture that gives the motor cortex the ability to execute movements on the basis of intention (the strategy of movement). In this context the cerebellum provides the tactics of the multiple muscle activation required to support such define movements. And so, while the motor brain determines where to move (executive imperative) the cerebellum implements its proper timing and modulates the force given to every motor command, as the coordination of movement is a non-continuous function.<ref> Llinas R. (1991) " The noncontinuous nature of movement execution. In: Motor Control: Concepts and Issues, eds. D.R. Humphrey and H.J. Freund, John Wiley & Sons Ltd., Dahlem Konferenzen pp 223-242" </ref>
==Dysfunction==
{{seemain|Ataxia}}
''Ataxia'' is a complex of symptoms, generally involving a lack of coordination, that is often found in disease processes affecting the cerebellum. To identify cerebellar problems, the [[neurological examination]] includes assessment of gait (a broad-based gait being indicative of ataxia), finger-pointing tests and assessment of posture.<ref name="Fine"/> Structural abnormalities of the cerebellum (hemorrhage, infarction, neoplasm, degeneration) may be identified on cross-sectional imaging. [[Magnetic resonance imaging]] is the modality of choice, as [[computed tomography]] is insufficiently sensitive for detecting structural abnormalities of the cerebellum.<ref>{{cite journal |author=Gilman S |title=Imaging the brain. Second of two parts |journal=N. Engl. J. Med. |volume=338 |issue=13 |pages=889–96 |year=1998 |pmid=9516225 |doi=}}</ref>
== Aging ==
A [[stereology|stereological]] study has found that human cerebellar [[white matter]] was reduced by 26% with [[aging|age]] (over the age range 19–84).<ref>{{Cite journal
| author = Birgitte Bo Andersen, [[Hans Jørgen G. Gundersen]], [[Bente Pakkenberg]]
| title = Aging of the human cerebellum: A stereological study
| journal = [[The Journal of Comparative Neurology]]
| volume = 466
| issue = 3
| year = 2003
| pages = 356–365
| doi = 10.1002/cne.10884
}}</ref>
The researchers of the study could detect no global loss of Purkinje or granule cells, however in the [[anterior lobe]] there was a significant loss of these cell types as well as a 30% volume loss.
With [[magnetic resonance imaging]] a moderate volumetric reduction with age in [[vermis]] and the cerebellar hemisphere has been observed.<ref>{{Cite journal
| author = Naftali Raz, Faith Gunning-Dixon, Denise Head, Adrienne Williamson & James D. Acker
| title = Age and Sex Differences in the Cerebellum and the Ventral Pons: A Prospective MR Study of Healty Adults
| journal = [[AJNR American Journal of Neuroradiology]]
| volume = 22
| pages = 1161–1167
| month = June/July
| year = 2001
| url = http://www.ajnr.org/cgi/reprint/22/6/1161.pdf
}}</ref>
An [[autoradiography]] study of the human cerebellum found an increasing [[binding (molecular)|binding]] of H-3-[[ketanserin]] with age.<ref>{{Cite journal
| author = Sharon L. Eastwood, Philip W. J. Burnet, Rebecca Gittins, Kate Baker, Paul J. Harrison
| title = Expression of 5-HT<sub>2A</sub> receptors in the human cerebellum and alterations in schizophrenia
| journal = [[Synapse (journal)|Synapse]]
| volume = 42
| issue = 2
| pages = 104–114
| month = November
| year = 2001
| doi = 10.1002/syn.1106
}}</ref>
(ketanserin binds primarily to the [[5-HT2A receptor|5-HT<sub>2A</sub> neuroreceptor]])
The same research team found no significant correlation with age in their [[homogenate binding]] study.
Somewhat in line with the autoradiography study a [[positron emission tomography]] study with the [[altanserin]] 5-HT<sub>2A</sub> receptor [[radioligand]]
found a positive correlation between age and cerebellar nonspecific binding.<ref>{{Cite journal
| author = K. H. Adams, Lars H. Pinborg, Claus Svarer, S. G. Hasselbalch, Søren Holm, S. Haugbøl, K. Madsen, Vibe G. Frøkjaer, L. Martiny, [[Olaf B. Paulson]], [[Gitte Moos Knudsen]]
| title = A database of [<sup>18</sup>F]-altanserin binding to 5-HT<sub>2A</sub> receptors in normal volunteers: normative data and relationship to physiological and demographic variables
| journal = [[Neuroimage]]
| year = 2004
| month = March
| volume = 21
| issue = 3
| pages = 1105–1113
| pmid = 15006678
| doi = 10.1016/j.neuroimage.2003.10.046
}}</ref>
==Theories about cerebellar function==
Two main theories address the function of the cerebellum, both dealing with motor coordination. One claims that the cerebellum functions as a regulator of the "timing of movements". This has emerged from studies of patients whose timed movements are disrupted.<!--
--><ref name="Ivry">{{cite journal | author=Ivry RB, Keele SW, Diener HC | title=Dissociation of the lateral and medial cerebellum in movement timing and movement execution | journal=Exp Brain Res | year=1988 | pages=167–80 | volume=73 | issue=1 | pmid=3208855 | doi = 10.1007/BF00279670 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
The second, "Tensor Network Theory" provides a mathematical model of transformation of sensory (covariant) space-time coordinates into motor (contravariant) coordinates by cerebellar neuronal networks.<!--
--><ref name="Neuroscience1980-Pellionisz">{{cite journal | author =Pellionisz, A., Llinás, R. | year =1980 | month = | title =Tensorial Approach To The Geometry Of Brain Function: Cerebellar Coordination Via A Metric Tensor | journal = Neuroscience | volume =5 | issue = | pages = 1125—-1136 | id = | url= http://usa-siliconvalley.com/inst/pellionisz/80_metric/80_metric.html | doi = 10.1016/0306-4522(80)90191-8 <!--Retrieved from CrossRef by DOI bot-->}}</ref><!--
--><ref name="Neuroscience1985-Pellionisz">{{cite journal | author = Pellionisz, A., Llinás, R. | year =1985 | month = | title= Tensor Network Theory Of The Metaorganization Of Functional Geometries In The Central Nervous System | journal = Neuroscience | volume =16 | issue =2 | pages = 245–273| url = http://usa-siliconvalley.com/inst/pellionisz/85_metaorganization/85_metaorganization.html | doi = 10.1016/0306-4522(85)90001-6 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
Like many controversies in the physical sciences, there is evidence supporting each of the above hypotheses. Studies of motor learning in the [[vestibulo-ocular reflex]] and [[eyeblink conditioning]] demonstrate that the timing and [[amplitude]] of learned movements are encoded by the cerebellum.<!--
--><ref name="Boyden"> {{cite journal | author=Boyden ES, Katoh A, Raymond JL | title=Cerebellum-dependent learning: the role of multiple plasticity mechanisms | journal=Annu Rev Neurosci | year=2004 | pages=581–609 | volume=27 | pmid=15217344 | doi = 10.1146/annurev.neuro.27.070203.144238 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
Many [[synaptic plasticity]] mechanisms have been found throughout the cerebellum. The Marr-Albus model mostly attributes motor learning to a single plasticity mechanism: the [[long-term depression]] of parallel fiber synapses. The Tensor Network Theory of sensorimotor transformations by the cerebellum has also been experimentally supported.<!--
--><ref name="Neuroscience1982-Pellionisz">{{cite journal | author=Pellionisz A, Llinas R | title=Space-time representation in the brain. the cerebellum as a predictive space-time metric tensor | journal=Neuroscience | year=1982 | pages=2949–70 | volume=7 | issue=12 | pmid=7162624 | doi = 10.1016/0306-4522(82)90224-X <!--Retrieved from CrossRef by DOI bot-->}}</ref><!--
--><ref name="Neuroscience1986-Gielen">{{cite journal | author=Gielen CC, van Zuylen EJ | title=Coordination of arm muscles during flexion and supination: application of the tensor analysis approach | journal=Neuroscience | year=1986 | pages=527–39 | volume=17 | issue=3 | pmid=3703248 | doi = 10.1016/0306-4522(86)90028-X <!--Retrieved from CrossRef by DOI bot-->}}</ref>
With the advent of more sophisticated [[neuroimaging]] techniques such as [[positron emission tomography]] (PET),<!--
--><ref name="Obayashi">{{cite journal | author=Obayashi S | title=Possible mechanism for transfer of motor skill learning: implication of the cerebellum | journal=Cerebellum | year=2004 | pages=204–11 | volume=3 | issue=4 | pmid=15686098 | doi = 10.1080/14734220410018977 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
and fMRI,<!--
--><ref name="Kim">{{cite journal | author=Kim SG, Ugurbil K, Strick PL | title=Activation of a cerebellar output nucleus during cognitive processing | journal=Science | year=1994 | pages=949–51 | volume=265 | issue=5174 | pmid=8052851 | doi = 10.1126/science.8052851 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
numerous diverse functions are now at least partially attributed to the cerebellum. What was once thought to be primarily a motor/sensory integration region is now proving to be involved in many diverse cognitive functions.
==Cerebellar modeling==
As mentioned in the preceding section, there have been many attempts to [[Mathematical model|model]] the cerebellar function.<!--
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The insights provided by the models have also led to extrapolations in the domains of [[artificial intelligence]] methodologies, especially [[neural networks]]. Some of the notable achievements have been ''Cerebellatron '',<!--
--><ref name="Lecturenotes-Hines">{{cite web | author = Dr Evor L. Hines | url = http://www.eng.warwick.ac.uk/eng/staff/elh/ise/session06/ise0629.html | title = Intelligent Systems Engineering - Major Characteristics of Expert Systems and Artificial Neural Networks | work = Intelligent Systems Engineering (ES3770) Lecture Notes | publisher School of Engineering, Warwick University = | accessdate=2006-03-28}}</ref>
''Cerebellar Model Associative Memory'' or ''CMAC'' networks,<!--
--><!-- [http://athene.riv.csu.edu.au/~dcornfor/Papers/Cornforth_ANNES2001_25.pdf] as of 2006-03-28 bad link -->
and ''SpikeFORCE'' for robotic movement control,<!--
--><ref name="SpikeFORCE">{{cite web | author = | authorlink = | coauthors = | year = | url = http://www.neuro-it.net/Activities/Alicante2003/spikeforce | title = SpikeFORCE: Real-time Spiking Networks for Robot Control | format = PDF | work = | publisher = | accessdate =2006-03-28 }}</ref>
and "Tensor Network Theory".<!--
--><ref name="EncNeuro-Pellionisz">{{cite book | last = Pellionisz | first = András J. | editor = George Adelman | chapter = Tensor Network Theory of the Central Nervous System | chapterurl = http://usa-siliconvalley.com/inst/pellionisz/encyclopaedia/encyclopaedia.html | pages = 1196–1198 | title =Encyclopedia of Neuroscience | edition=II | publisher =Birkhauser}}</ref>
==Additional images==
<gallery>
Image:CT of brain of Mikael Häggström S3 I8.JPG|[[Computed tomography]] of head, with cerebellum visible at lower part.
Image:Illu cerebrum lobes.jpg|Lobes
Image:Illu diencephalon .jpg|Diencephalon
Image:Gray677.png|Scheme showing the connections of the several parts of the brain.
Image:Gray702.png|Upper surface of the cerebellum.
Image:Gray703.png|Under surface of the cerebellum.
Image:Gray704.png|Sagittal section of the cerebellum, near the junction of the vermis with the hemisphere.
Image:Gray705.png|Dissection showing the projection fibers of the cerebellum.
Image:Gray708.svg|Scheme of roof of fourth ventricle. The arrow is in the foramen of Majendie.
Image:Gray745.png|Dissection showing the course of the cerebrospinal fibers.
Image:Gray768.png|Diagram showing the positions of the three principal subarachnoid cisternæ.
Image:Human cerebellum anterior view description.JPG|Human cerebellum anterior view
Image:Human brain midsagittal view description.JPG|Human brain midsagittal view
</gallery>
==See also==
*[[Posterior cranial fossa]]
*[[Brain]]
*[[Central nervous system]]
*[[List of regions in the human brain|Regions in the human brain]]
==External links==
*A worldwide list of {{wayback|cerebellum.stanford.edu/ |laboratories that do research on the cerebellum}}
*[http://socrates.berkeley.edu/~ivrylab/research/cerebellum+timing.html Cerebellum and timing] at [[University of California, Berkeley]]
*[http://www.mult-sclerosis.org/cerebellum.html Cerebellum and multiple sclerosis] at mult-sclerosis.org
*[http://thalamus.wustl.edu/course/cerebell.html Basal ganglia and cerebellum] at [[Washington University in St. Louis]]
*[http://www.newhorizons.org/neuro/leiner.htm "The Treasure at the Bottom of the Brain”] at newhorizons.org
*[http://biology.about.com/library/organs/brain/blcerebellumimage.htm Cerebellum images] at [[About.com]]
* {{BrainMaps|cerebellum}}
*[http://www.ii.bham.ac.uk/clinicalimmunology/Neuroimmunology/cerebellum.htm Histological section of primate cerebellum] at [[University of Birmingham]]
*[http://www.mona.uwi.edu/fpas/courses/physiology/neurophysiology/Cerebellum.htm Cerebellum and Motor Control], Neurophysiology Lecture Site, Ronald E. Young, Ph.D., University of West Indies, Mona.
==Further reading==
<div class="references-small">
* Ito M. ''Cerebellum and Neural Control''. New York: Raven Press; 1984. ISBN 0-89004-106-7
* [[Eric R. Kandel|Kandel ER]], Schwartz JH, Jessell TM. ''[[Principles of Neural Science]]'', 4th ed. McGraw-Hill, New York (2000). ISBN 0-8385-7701-6
* Llinás, R, Sotelo C. ''The Cerebellum Revisited''. New York: Springer; 1992. ISBN 0-387-97693-0
* Parent A, Carpenter MB. ''Carpenter's Human Neuroanatomy''. 9th ed. Philadelphia: Williams and Wilkins; 1995. ISBN 0-683-06752-4
</div>
==References==
{{Reflist|2}}
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[[Category:Cerebellum|*]]
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