The dentate nucleus is located within the deep white matter

White matter

White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...

 of each cerebellar hemisphere, and it is the largest single structure linking the cerebellum

Cerebellum

The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

 to the rest of the brain. It is the largest and most lateral, or farthest from the midline, of the four pairs of deep cerebellar nuclei

Deep cerebellar nuclei

The Cerebellum has four deep cerebellar nuclei embedded in the white matter in its center.-Inputs:These nuclei receive inhibitory inputs from Purkinje cells in the cerebellar cortex and excitatory inputs from mossy fiber and climbing fiber pathways. Most output fibers of the cerebellum originate...

, the others being the fastigial and the interposed

Interposed nucleus

The interposed nucleus is a deep nucleus of the cerebellum and is composed of the globose nuclei and the emboliform nuclei. It is located in the roof of the fourth ventricle, lateral to the fastigial nucleus...

 nuclei (globose and emboliform nuclei combined). The dentate nucleus is responsible for the planning, initiation and control of voluntary movements. The dorsal region of the dentate nucleus contains output channels involved in motor function, which is the movement of skeletal muscle

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

, while the ventral region contains output channels involved in nonmotor function, such as conscious thought and visuospatial function.

Development

The dentate nucleus is highly convoluted, and gyral, or groove, formation is coincident with a critical period of extensive growth in the fetal dentate. The dentate nucleus becomes visible in the cerebellar white matter as early as 11-12 weeks of gestation, containing only smooth lateral and medial surfaces. During this time, the neurons of the dentate nucleus are similar in shape and form, being mainly bipolar cells.

During 22-28 weeks of gestation, which is the critical period in fetal development of the dentate nucleus, gyral formation occurs extensively over the entire surface. Here, neurons mature into various forms of multipolar cells

Multipolar neuron

A multipolar neuron is a type of nig that possesses a single axon and many dendrites, allowing for the integration of a great deal of information from other neurons. These dendritic branches can also emerge from the nerve cell body...

, and the most frequent neuronal types are medium sized to large neurons.

Location

The architecture of cerebellum is very crystallized, so a slice in the cerebellum anywhere gives repeated architecture. The eight cerebellar nuclei, located within the deep white matter of each cerebellar hemisphere, are grouped into pairs. From the midline, the dentate nucleus is the most lateral, then the interposed nucleus, and the fastigial nucleus is the most medial. As a chunk of tissue, the dentate nucleus with overlying cerebellar cortex makes up a functional unit called the cerebrocerebellum. Thus, there is a part of cerebellum that communicates exclusively with the dentate nucleus.

Deep cerebellar nuclei

• Dentate: The dentate nucleus is the largest, most lateral, and phylogenetically most recent of the cerebellar nuclei. It receives afferent, or incoming, signals from the premotor cortex and supplementary motor cortex via the pontocerebellar system. Efferent, or outgoing, signals travel via the superior cerebellar peduncle through the red nucleus
  Red nucleus
  The red nucleus is a structure in the rostral midbrain involved in motor coordination. It comprises a caudal magnocellular and a rostral parvocellular part.-Function:...
  
   to the ventrolateral thalamus
  Thalamus
  The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
  
  .
• Interposed: The interposed nucleus is the smallest of the cerebellar nuclei, located between the denate and fastigial. The globose and emboliform nuclei together make up the interposed nucleus. It receives afferent supply from the anterior lobe of the cerebellum and sends output via the superior cerebellar peduncle to the red nucleus.
• Fastigial: The fastigial nucleus is the most medial. It receives afferent input from the vermis, and efferents travel via the inferior cerebellar peduncle to the vestibular nuclei
  Vestibular nuclei
  The vestibular nuclei are the cranial nuclei for the vestibular nerve.In Terminologia Anatomica they are grouped in both the pons and medulla.-Subnuclei:There are 4 subnuclei; they are situated at the floor of the fourth ventricle....
  
  .

The deep cerebellar nuclei receive the final output from the cerebellar cortex via Purkinje cells in the form of inhibition. Neurons in the cerebellar nuclei generate spontaneous action potentials despite ongoing inhibition from Purkinje cells. The cerebellar nuclei receive afferent projections from the inferior olive, lateral reticular nucleus

Lateral reticular nucleus

The lateral reticular nucleus, of the funiculus, can be divided into three subnuclei, the parvocellular, magnocellular and the subtrigeminal. As is typical of the reticular formation, none of these are very distinct subnuclei, but rather blurred distinctions between cell types and location...

, upper cervical and lumbar spinal segments, and the Pontine nuclei

Pontine nuclei

The pontine nuclei are a part of the pons involved in motor activity. Corticopontine fibres carry information from the primary motor cortex to the ipsilateral pontine nucleus in the ventral pons, and the pontocerebellar projection then carries that information to the contralateral cerebellum via...

. Together, the deep cerebellar nuclei form a functional unit that provides feedback control of the cerebellar cortex by cerebellar output.

Morphology

The dentate nucleus is highly convoluted and can be divided into dorsal (motor) and ventral (nonmotor) domains. The ventral half is much more developed in humans than in great apes, and it appears to play an important role in fiber connection. Further, the ventral domain mediates higher cerebellar functions, such as language and cognition, as well as versatile and coordinated finger movement. While it is generally accepted that the ventral region is more recent on an evolutionary timescale, current 3-Dimensional imaging raises questions regarding this assumption, as a third axis, the rostrocaudal axis, can now be analyzed. In addition, current images show that the ventral region is not physically larger than the dorsal region in humans, as would be predicted if size increases with cognitive function.

The neurons of the adult dentate are divided based on size, morphology, and function into large principal and small local circuit neurons.

Large principal neurons

The large principal neurons have been classified into four primary types according to position within the dentate, shape of soma (cell body), and dendritic

Dendrite

Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

 branching. These neurons are responsible for communication between the dentate nucleus and the cerebellar cortex.

• Central neurons: The central neurons are located in deeper parts of the nuclear mass, away from the periphery. They have round and prickly somata, and numerous dendritic trunks emerge from every direction of the soma. These dendrites have complex branching patterns and spherical dendritic fields.
• Border neurons: The border neurons are concentrated at the boundary of the nuclear lamina
  Nuclear lamina
  The nuclear lamina is a dense fibrillar network inside the nucleus of a eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division...
  
   and have elliptical somata. They have a stout axon directed into the surrounding white matter, as well as four to six primary dendrites that branch from the opposite end. The dendritic fields of these neurons have a tetrahedron shape with the cell body in one corner.
• Intermediate asymmetric neurons: The intermediate asymmetrical neurons are evenly distributed throughout the nuclear mass, and they have large, elliptical somata. They have five to nine dendrites branching in all directions, with one or two much longer than the others.
• Intermediate fusiform neurons: The intermediate fusiform neurons are scattered throughout the dentate, and they have elongated and elliptical somata which are tapered at both ends. They include three to five primary dendrites which divide into several long dendrites. The upper part of the cell body is parallel to the apical dendrites, which are oriented toward the nuclear core.

Small local circuit neurons

Small local circuit neurons include signaling pathways that are contained within the dentate. These neurons provide feedback to the dentate and allow for fine control of signaling. Currently, less research has been conducted on the specific shape and role of these neurons, as the dentate nucleus is composed primarily of large principal neurons.

Projections

The dentate contains anatomically separate and functionally distinct motor and nonmotor domains (dorsal and ventral, respectively), and projections are organized from the dentate nucleus to distinct areas in the ventrolateral thalamus. In addition, the dorsal parts of the dentate project to the primary motor

Primary motor cortex

The primary motor cortex is a brain region that in humans is located in the posterior portion of the frontal lobe. Itworks in association with pre-motor areas to plan and execute movements. M1 contains large neurons known as Betz cells, which send long axons down the spinal cord to synapse onto...

 and premotor areas of the cerebral cortex

Cerebral cortex

The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

, while the ventral parts of the dentate project to prefrontal and posterior parietal areas of the cerebral cortex. The motor and nonmotor domains make up approximately 50-60 percent and 20 percent, respectively, of the dentate in monkeys. It is estimated that the human dentate proportions are comparable. All cerebral cortical areas that are targeted by the dentate project back on the cerebellum via efferents to Pontine nuclei, and cortical areas that do not project onto the cerebellum are not targets of dentate output.
The motor domain in the dorsal portion of the dentate contains output channels that control both generation and control of movement, as well as neurons that innervate premotor areas in the frontal lobe

Frontal lobe

The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...

.
The nonmotor domain contains output channels involved in cognition and visuospatial function, and projections to the prefrontal and posterior parietal cortical areas within this region are clustered into distinct regions with little overlap. These areas are activated during tasks involving short-term working memory, rule-based learning, and higher executive function-like planning. Although the ventral aspect of the dentate has been shown to be involved in acquisition of information, whether it is involved in retention and storage remains unclear.

Pathways

There are three distinct routes from the dentate nucleus to the ventrolateral thalamus, including a direct, posterior, and anterior route. The direct route passes in the anterolateral direction under the thalamus and enters from the ventral side. Axons following the posterior pathway turn dorsally from the midline at the posterior side of the thalamus, entering the thalamus from various positions. Axons following the anterior route pass laterally in the subthalamus and enter the external medullary lamina

Medullary laminae of thalamus

Medullary laminae of thalamus are layers of myelinated fibres that appear on cross sections of the thalamus. They also are commonly referred to as laminae medullares thalami or medullary layers of thalamus...

. Within the lamina, fibers turn posteriorly and enter the dorsal side of the thalamus. Therefore, as a result of these various pathways, the neurons of the dentate nucleus are able to traverse all thalamic nuclei, with the exception of those at the midline and anterior nuclear groups.

Dentate nucleus axons can be divergent or convergent. Convergent branches include those that originate from entirely different axons and traverse different routes, yet overlap on the same terminal field. Divergent pathways originate from the same axon but travel different routes and target different terminal fields. Although no point-to-point connectivity has been observed between the dentate nucleus and the thalamus, it is believed that there is a pre-wired connectivity between a single dentate site and several body part representations in the thalamus.

Three modalities are received by cerebellum, including proprioception

Proprioception

Proprioception , from Latin proprius, meaning "one's own" and perception, is the sense of the relative position of neighbouring parts of the body and strength of effort being employed in movement...

, nociception

Nociception

Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...

, and somatic

Somatosensory system

The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...

 input, and all of these stimulate the dentate nucleus. The dentate nucleus is mostly responsible for planning and execution of fine movement. Since any motor function requires sensory information, it can be assumed that the dentate nucleus receives and modulates this sensory information, though the specific mechanism of this remains unclear. For example, the act of lifting an object requires sensory input, such as the size of the object and where it is located in space. While the primary role of the dentate nucleus is control of the movement, it does play a role in sensory processing as well.

Role

The role of the dentate nucleus can be described in two basic tenets:

1. The dentate nucleus is involved in basic circuitry work, including input to the cerebellum from everywhere else. Any function that needs coordination, including thoughts and motor behavior, must go through the cerebellum to be smoothened. This input travels in two parts, to the surface of the cerebellar cortex as well as collateral input to the cerebellar nuclei.
2. The whole cerebellum has only one output, which necessarily leads from the deep cerebellar nuclei. There is output from the cerebellar cortex, so this output must go through the cerebellar nuclei and send output to rest of nervous system. Thus, the cerebellum communicates to the outside world via the cerebellar nuclei. Input that reaches the cerebellar cortex is processed in many ways; eventually whatever happens in cerebellar cortex exits the cerebellum through a synapse in the cerebellar nuclei.

The dentate nucleus is responsible for the planning, initiation and control of voluntary movements. The dorsal region of the dentate contains output channels involved in motor function, while the ventral region contains output channels involved in nonmotor function, such as cognition and visuospatial function. The dentate nucleus sends commands and information to the motor and premotor areas in the forebrain.

Disorders

Several pathological processes involve the dentate nucleus including metabolic, genetic, and neurodegenerative disorders, as well as some infections.

Metabolic disorders

Maple syrup urine disease

Maple syrup urine disease

Maple syrup urine disease , also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia...

 (MSUD): An inherited disorder of amino acid metabolism in newborns, MSUD results in neurological deterioration. Myelin edema

Edema

Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

 is seen in the cerebellum, including the dentate nucleus, brain stem

Brain stem

In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...

, and corticospinal tracts.

Leigh disease: Clinical and pathological symptoms usually appear in the first year of life and include psychomotor retardation and brain stem dysfunction. Bilaterally symmetric defects are seen in the periaqueductal grey matter, brain stem, basal ganglia

Basal ganglia

The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...

, and dentate nucleus.

Glutaric aciduria type 1 (GA1): An autosomal recessive disease, GA1 is due to glutaryl-coenzyme A dehydrogenase

Glutaryl-CoA dehydrogenase

Glutaryl-CoA dehydrogenase is an enzyme acting upon glutaryl-coenzyme A, creating crotonyl-coenzyme A.It plays a role in the metabolism of lysine, hydroxylysine and tryptophan.-Pathology:...

 deficiency. Abnormalities are seen in the basal ganglia and dentate nucleus.

Canavan's disease: Canavan’s disease is a white matter disease due to aspartoacylase

Aspartoacylase

Aspartoacylase is a hydrolase enzyme which breaks down N-acetylaspartate. A deficiency is associated with Canavan disease....

 deficiency. The dentate nucleus is not affected until late in disease progression.

Miscellaneous disorders

Neurofibromatosis type 1 (NF1): NF1 is an autosomal dominant neurocutaneous disorder. The hallmark of NF1 is the development of numerous tumors. Cerebellar white matter and dentate nucleus lesions usually occur in children less than ten years of age.

Langerhans cell histiocytosis

Langerhans cell histiocytosis

Langerhans cell Histiocytosis is a rare disease involving clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes...

 (LCH): LCH is an aggressive disorder due to proliferation of Langerhans cell hystiocytes, and the dentate nucleus is believed to be involved in up to 40 percent of patients.

Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

 (AD) with myoclonus

Myoclonus

Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...

: There is an increase in mean volume of large neurons and a decrease in mean volume of small neurons in the dentate nucleus in AD with myoclonus. Morphological changes in the dentate nucleus may contribute to the pathological substrate of myoclonus in AD.

See also

• Cerebellum
  Cerebellum
  The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
  
  
• Cerebellar cortex
• Deep cerebellar nuclei
  Deep cerebellar nuclei
  The Cerebellum has four deep cerebellar nuclei embedded in the white matter in its center.-Inputs:These nuclei receive inhibitory inputs from Purkinje cells in the cerebellar cortex and excitatory inputs from mossy fiber and climbing fiber pathways. Most output fibers of the cerebellum originate...
  
  
• Cerebral cortex
  Cerebral cortex
  The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
  
  
• Thalamus
  Thalamus
  The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
  
  

External links

• http://www.mona.uwi.edu/fpas/courses/physiology/neurophysiology/Cerebellum.htm
• http://www.neuroanatomy.wisc.edu/cere/text/P5/dentate.htm
• NIF Search - Dentate Nucleus via the Neuroscience Information Framework
  Neuroscience Information Framework
  The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/genomic resources.-Description:...