Cerebellum
For assistance with anatomical location terms, see Anatomical terms of location
The cerebellum (literally "little brain") is a brain region important for the integration of sensory perception with motor output. The numerous loops both within and through the cerebellum with the motor cortex and spinocerebellar tracts indicate the cerebellum is as an integrative region whose purpose it the modulation of function. Lesions of the cerebellum do not cause paralysis but rather cause feedback deficits manifesting as disorders in fine movement, equilibrium, posture, and motor learning.
The cerebellum is also thought to play a role in certain cognitive functions including attention, language processing, music understanding, and sensory temporal processing.
General features
The Cerebellum is located in the inferior posterior portion of the head (the hindbrain), directly dorsal to the brainstem and pons, inferior to the occipital lobe. Due to the large number of tiny granule cells, the cerebellum contains nearly 80% of all the neurons in the brain despite constituting only 10% of the total brain volume. It receives nearly 200 million input fibres (in contrast, the optic nerve has a mere 1 million fibers).
The cerebellum is divided into two large hemispheres much like the cerebrum, and contains ten smaller lobules. The cytoarchitecture (cellular organization) of the cerebellum is very uniform, with connections organized into a rough three-dimensional array of perpendicular circuit elements. The circuits in the cerebellar cortex look similar across all classes of vertebrates including fish, reptiles, birds, and mammals, including humans. This has been taken as evidence that the cerebellum performs an evolutionarily primitive function important to all vertebrate species.
Development and Evolution
The embryonic cerebellum develops from the superior dorsal aspect of the rhombencephalon. In the mature mammalian brain, the cerebellum comprises a distinct structure at the back of the brain. The cerebellum is of archipalliar phylogenetic origin, shared as a prototypical brain structure by animals from the most elementary to the most advanced.
The cerebellum arises from two rhombomeres in the alar plate of the neural tube: rhombomere 1 (Rh.1) caudally, and the isthmus rostrally [1]. In general, the alar plate gives rise to sensory structures sugesting that the cerebellum may be sensory in nature. However the cerebellum is well known to perform a combination of sensory and motor functions.
There are two primary regions that are thought to give rise to neurons that make up the cerebellum. The first region is the ventricular zone (the roof of the fourth ventricle). This area produces Purkinje cells and deep cerebellar nuclear neurons. These cells are the primary output neurons of the cerebellar cortex and cerebellum (respectively). The second germinal zone is known as the external granular layer (EGL). This layer of cells — found on the exterior the cerebellum — produces the cells known as granule neurons. Once born, the granule neurons migrate from this exterior layer to form the inner layer known as the internal granule cell layer (IGL). Once the cerebellum has reached maturity the EGL ceases to exist, leaving only granule cells in the IGL. The cerebellar white matter is perhaps a third germinal zone in the cerebellum; however this germinal zone is somewhat controversial.
Anatomy
The cerebellum contains similar grey and white matter divisions as the cortex.
Embedded within the white matter — known as the arbor vitae (Tree of Life) in the cerebellum due to its branched, tree-like appearance — are four deep cerebellar nuclei.
There are three gross phylogenetic segments that are largely grouped by general function. The three cortical layers contain various cellular types that often create various feedback and feedforward loops.
Oxygenated blood is supplied by arterial branches off the basilar and vertebral arteries.
Divisions
There are three phylogenetic lobes: the flocculonodular (archicerebellum), anterior (paleocerebellum), and posterior (neocerebellum) cerebellar lobes. The anterior and posterior lobes are separated by the primary fissure. The posterior and flocculonodular lobes are separated by the posterolateral fissure.
There are also three functional divisions that are perpendicular to the phylogenetic lobes. The midline division is called the cerebellar vermis (“worm”) due to its long, slender shape. The vermis has many subdivisions: the lingula, central lobule, and culmen (anterior); the declive, tuber, pyramid, uvula, and nodule (posterior). The region just lateral to the vermis is called the intermediate zone; the most lateral region is the lateral zone.
Archicerebellum
The archicerebellum is associated with the flocculonodular lobe and is mainly involved in vestibular and eye movement functions. It receives input from the inferior and medial vestibular nuclei and sends fibers back to the vestibular nuclei creating a feedback loop. Archicerebellar lesions cause motor symptoms not unlike those seen during intoxication: uncoordinated movements, swaying, unstable walking, and a wide gait. In the United States, patients suffering archicerebellar lesions carry identification cards indicating the nature of their medical condition so as to avoid suspicion of public drunkenness by the police.
Paleocerebellum
The paleocerebellum is associated with the anterior lobe. Its function is proprioception (sense of body position) related to muscle tone (constant, partial muscle contraction important for maintenance of posture). It receives its inputs from the posterior and anterior spinocerebellar tracts, and sends axonal projections to the deep cerebellar nuclei. Lesions to this region cause a severe disturbance in muscle tone and bodily posture.
Neocerebellum
The neocerebellum is associated with the posterior lobe. It receives input from the pontocerebellar tract, with its efferents synapsing within the deep cerebellar nuclei. The pontocerebellar tract originates at the pontine nuclei, which receive their input from the cerebral motor cortex. Thus, the neocerebellum is associated with motor control, specifically in coordinating fine finger movements (such as playing the piano). Neocerebllar lesions are associated with deficits in skilled voluntary movement.
Deep Nuclei
The four deep cerebellar nuclei are located in the center of the cerebellum, embedded within the white matter. These nuclei receive inhibitory ( GABAergic) inputs from Purkinje cells in the cerebellar cortex and excitatory ( glutamatergic) inputs from mossy fiber pathways; these nuclei constitute the sole output of the cerebellum.
The four nuclei are known as the dentate, emboliform, globose, and fastigial nuclei. An easy mnemonic device to remember these names and positions relative to their position from the midline is the phrase "Don't Eat Greasy Food", where each letter indicates the lateral to medial location within the cerebellar white matter. The nonhuman analogue of the emboliform and globose nuclei is a single, fused nucleus interpositus (interposed nucleus). The vestibular nuclei in the brainstem are analogous structures to the deep nuclei and receive inputs from the flocculonodular lobe of the cerebellum.
Cortical Layers
The cerebellar cortex has three layers. From outer to inner layer they are the: molecular; Purkinje, and granular layers.
Granular Layer
The innermost layer contains the cell bodies of two types of cells: the numerous and tiny granule cells as well as the larger Golgi cells.
Mossy fibers enter the granular layer from their main point of origin, the pontine nuclei. These fibers make excitatory synapses with the granule cells as well as the cells of the deep cerebellar nuclei. The granule cells send their axons — known as parallel fibers — up into the superficial molecular layer where they form hundreds of thousands of synapses with Purkinje cell dendrites.
Humans are estimated to have on the order of 1010 granule cells.
Golgi cells provide inhibitory feedback to granule cells, forming a synapse with the granule cell and sending 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 cell dendrites are large arbors with hundreds of branches reaching up into the molecular layer. These dendritic arbors are flat — nearly all in plane — with neighboring Purkinje arbors in parallel planes. The parallel fibres from the granule cells run orthogonally through these arbors like a wire passing through many layers. Purkinje neurons send inhibitory signals through their sole projections to the deep cerebellar nuclei, or directly to vestibular nuclei in the brainstem.
Each Purkinje cell receives excitatory input from 100,000-200,000 parallel fibres. Parallel fibres are said to be responsible for simple spiking of the Purkinje cell.
Purkinje cells also receive input from the inferior olivary nucleus via climbing fibres. A good mnemonic to remember this interaction is the phrase “climb the olive tree”, given that climbing fibres originate from the inferior olive. Each Purkinje cell receives input from a single climbing fiber, in the form of a powerful excitatory signal. Climbing fiber inputs generate a complex excitatory post-synaptic response in the Purkinje neuron. These responses are known as complex spikes.
Molecular Layer
This outermost layer of the cerebellar cortex is made up of two types of inhibitory interneurons: the stellate cells and the basket cells. It also contains the dendritic arbors of Purkinje neurons and parallel fiber tracts from the granule cells. Both stellate and basket cells form GABAergic — or inhibitory — synapses onto Purkinje dendrites.
Peduncles
Again 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.
There are three sources of input to the cerebellum in two categories consisting of mossy and climbing fibers. Mossy fibers originate either from pontine nuclei originating within the pons and carrying information from the contralateral cerebral cortex or from the spinocerebellar tract originating from the ipsilateral spinal cord.
The majority of the output from the cerebellum first synapses onto the deep cerebellar nuclei before exiting via the three peduncles. The most notable exception would be direct inhibition of the vestibular nuclei by Purkinje cells.
Superior Cerebellar Peduncle
The superior cerebellar peduncle contains both input and output pathways. The afferent fibers are mainly composed of fibers of the anterior spinocerebellar tract and are conveyed to the anterior cerebellar lobe. The majority of the efferent pathway sends fibers from the dentate nucleus to various midbrain structures including the red nucleus, ventrolateral nucleus of the thalamus, and the medulla.
Middle Cerebellar Peduncle
The middle cerebellar peduncle only carries afferent fibers originating at the pontine nuclei into the cerebellum. These fibers descend from the sensory and motor areas of the cerebral neocortex and make the middle cerebellar peduncle the largest of the three cerebellar peduncles.
Inferior Cerebellar Peduncle
The inferior cerebellar peduncle carries many different types of input and output fibers mainly concerned with integrating proprioceptive sensory input with motor vestibular functions such as balance and posture maintenance. Proprioceptive information from the body is carried to the cerebellum via the posterior spinocerebellar tract. This tract passes through the inferior cerebellar peduncle and synapses within the paleocerebellum. Vestibular information projects onto the archicerebellum. This peduncle also carries information directly from the Purkinje cells to the vestibular nuclei located in the dorsal brainstem, spanning between the pons and medulla.
Blood Supply
Three arteries supply blood to the cerebellum: 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 junction of the vertebral arteries. From its origin it branches along the most 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 as well as the facial (CN VII) and vestibulocochlear nerves (CN VIII). Obstruction of this artery can cause facial paresis, paralysis, and loss of sensation as well as hearing impairment.
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, PICA sends branches into the medulla supplying blood to several cranial nerve nuclei. In the cerebellum it supplies blood to the posterior inferior portion of the cerebellum, the inferior cerebellar peduncle, nucleus ambiguus, vagus motor nucleus, spinal trigeminal nucleus, solitary nucleus, and vestibulocochlear nuclei.
Because of the numerous nuclei that receive blood from PICA, an obstruction or ischemia of this artery can cause a wide range of symptoms (see Cerebellum#Dysfunctions below).
Dysfunctions
Patients with cerebellar dysfunction have problems with walking, balance, and accurate hand and arm movements. Recent brain imaging studies (using fMRI) show that the cerebellum is important for language processing and selective attention. The cerebellum is thought to be deficient in neuropsychiatric disorders such as dyslexia and autism. It is also important in development of certain ataxias, including a form of cerebral palsy. Spinocerebellar ataxia patients suffer a degeneration of the cerebellum.
Lesions of the Cerebellum
Patients with cerebellar lesions generally exhibit deficits during movement execution. For example, they show “intention tremors” — a tremor occurring only during movement rather than at rest (as seen in Parkinson’s Disease). Patients may also show dysmetria, which is an overestimation or underestimation of force. This results in over-shoot or under-shoot when reaching for a target. Another common sign of cerebellar damage is an inability to perform rapid alternating movements.
Alcohol abuse leads to degeneration of the anterior cerebellum which leads to a wide staggering gait but does not affect arm movements or speech. The anterior and medial aspects of the cerebellum represent information ipsilaterally, so damage to this region on one side affects the movement on the same side of the body. The posterior and lateral aspects of the cerebellum represent information bilaterally and damage to this region has been shown to impair sensory-motor adaptation, while leaving motor control unaffected.
Ischemia and Thrombosis
An obstruction of the posterior inferior cerebellar artery (PICA syndrome) can cause a wide range of characteristic effects. There can be loss of sensation to the contralateral limbs due to inferior cerebellar peduncle as well as dizziness and nausea due to loss of blood to the nucleus ambiguus and vestibulocochlear nuclei.
Theories about Cerebellar Function
Two main theories address the function of the cerebellum. 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 1.
The other claims that the cerebellum operates as a learning machine, encoding information like a computer. This was first proposed by Marr and Albus in the early 1970s 2.
Like many controversies in biology, there is evidence supporting parts of both hypotheses. Studies of motor learning in the vestibulo-ocular reflex and eyeblink conditioning demonstrate that timing and amplitude of learned movements are encoded by the cerebellum 3. Many synaptic plasticity mechanisms have been found throughout the cerebellum. The Marr-Albus model mostly attributes motor learning to a single plasticity mechanism, long-term depression of parallel fiber synapses.
See Also
External Links
- A list of laboratories that do research on the cerebellum, around the world.
- Brain Atlas, Brain Maps, Neuroinformatics
References
- Ivry RB, Keele SW, Diener HC (1988) Dissociation of the lateral and medial cerebellum in movement timing and movement execution. Exp Brain Res 73(1): 167-80
- Marr D (1969) A theory of cerebellar cortex. J Physiol 202(2): 437-70
- Boyden ES, Katoh A, Raymond JL (2004) Cerebellum-dependent learning: The role of multiple plasticity mechanisms. Annu Rev Neurosci 27: 581-609.
- Ito, M. Cerebellum and Neural Control.1984. Raven Press. ISBN 0890041067
- Eric Kandel, James Schwartz, and Thomas Jessel. 2000. Principles of Neural Science. 4th ed. McGraw-Hill, New York. ISBN 0838577016
- Parent, A., Carpenter, M.B. 1995. Carpenter's Human Neuroanatomy. 9th ed. Williams and Wilkins. ISBN 0683067524