The inferior olivary nucleus (ION) is a structure found in the

medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...

underneath the superior olivary nucleus.Gado, Thomas A. Woolsey; Joseph Hanaway; Mokhtar H. (2003). The brain atlas a visual guide to the human central nervous system (2nd ed.). Hoboken, NJ: Wiley. p. 206. . In vertebrates, the ION is known to coordinate signals from the spinal cord to the cerebellum to regulate

motor coordination In physiology, motor coordination is the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. This coordination is achieved by adjusting kinematic and kinetic parameters associated with each bo ...

and learning.Schweighofer N, Lang EJ, Kawato M. Role of the olivo-cerebellar complex in motor learning and control. ''Frontiers in Neural Circuits''. 2013;7:94. . These connections have been shown to be tightly associated, as degeneration of either the cerebellum or the ION results in degeneration of the other. Neurons of the ION are

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

and receive inhibitory input via

GABA receptors The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

. There are two distinct GABAα receptor populations that are spatially organized within each neuron present in the ION. The GABAα receptor make-up varies based on where the receptor localizes on the ION neuron.Alastair M. Hosie, Megan E. Wilkins, Helena M. A. da Silva & Trevor G. Smart. ''Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites''. Nature 444, 486-489. The reason for this spatial distribution is unknown. It has been proposed that the distinct populations of GABAα receptors allows for fine-tuned regulation within the ION.

Structure

The inferior olivary nucleus (ION) has a distinct laminar structure. It is located posterior to the pyramid but anterior to the inferior cerebellar peduncle. These lamina house the cell bodies of the olivocerebellar fibers. These neurons are the major input source for the

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

. Their axons are referred to as

climbing fiber Climbing fibers are the name given to a series of neuronal projections from the inferior olivary nucleus located in the medulla oblongata. These axons pass through the pons and enter the cerebellum via the inferior cerebellar peduncle wher ...

s. These climbing fibers leave the ION medially through the hilum, cross the midline, and ascend into the cerebellum via the

inferior cerebellar peduncle The inferior cerebellar peduncle is formed by fibers of the restiform body that join with fibers from the much smaller juxtarestiform body. The inferior cerebellar peduncle is the smallest of the three cerebellar peduncles. The upper part of t ...

. The target for each climbing fiber is a specific neuron in the cerebellum referred to as a

Purkinje Cell Purkinje cells or Purkinje neurons, named for Czech physiologist Jan Evangelista Purkyně who identified them in 1837, are a unique type of prominent, large neuron located in the Cerebellum, cerebellar Cortex (anatomy), cortex of the brain. Wi ...

. During development, there are multiple climbing fibers on a purkinje cell, however these are pruned off during postnatal development, thus leaving a mature purkinje cell with a single climbing fiber. There are three major components of the IO. # Primary olivary nucleus (PO) – This is the major laminar structure, and its distinct folds can be seen clearly. #* The PO receives signals from other components of the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

, such as the

red nucleus The red nucleus or nucleus ruber is a structure in the rostral midbrain involved in motor coordination. The red nucleus is pale pink, which is believed to be due to the presence of iron in at least two different forms: hemoglobin and ferritin. ...

and the N. Darkschewitsch. The PO also receives signals from the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

. #* The PO targets the intermediate cerebellum as well as the

cerebellar hemisphere The cerebellum consists of three parts, a median and two lateral, which are continuous with each other, and are substantially the same in structure. The median portion is constricted, and is called the vermis, from its annulated appearance which ...

s. # Medial accessory olivary nucleus (MAO) – This nucleus is between the PO and the pyramids. It is visualized as a curved lamina. #* The MAO receives signals from the

tectum The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum. It is functionally associated with vision, hearing, mo ...

and the

pretectum In neuroanatomy, the pretectal area, or pretectum, is a midbrain structure composed of seven nuclei and comprises part of the subcortical visual system. Through reciprocal bilateral projections from the retina, it is involved primarily in mediati ...

. #* Climbing fibers from the MAO synapse with the

vermis The cerebellar vermis (from Latin ''vermis,'' "worm") is located in the medial, cortico-nuclear zone of the cerebellum, which is in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior s ...

, the flocculus, and the cerebellar hemispheres # Dorsal accessory olivary nucleus (DAO) – This nucleus also is a curved lamina. It is the smallest nucleus in the IO and is behind the PO. #* The DAO receives signals from the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

and the dorsal column nuclei. #* The DAO synapses with vermis.

Function

Motor coordination and learning

Patient studies revealed the connection between the inferior olivary nucleus (ION) and the cerebellum. Lesions in the ION impair the ability to learn higher level motility, such as performing a perfect jumpshot. Further investigation of the neuroanatomy confirmed the intimate connection between the IO and the cerebellum in motor coordination and learning. The IO sends signals to the cerebellum based on information sent from the

spino-olivary tract The spino-olivary tract (historically Helweg's tract) is located in the anterior funiculus of the spinal cord and provides transmission of unconscious proprioception and is involved in balance. This nerve tract, tract carries proprioception info ...

. Regulation following this point is highly debated. The original hypothesis as to how the IO influenced the cerebellum involved long term depression (LTD). In this scenario, deep cerebellar nuclei send GABA projection to inhibit ION. More recent studies suggest that encoding the timing of sensory input is the key component of these connections.Liu T, Xu D, Ashe J, Bushara K. Specificity of inferior olive response to stimulus timing. J Neurophysiol 2008; 100: 1557-61. The ION sends signals through different cell clusters. These signals vary in location and in frequency bundles and appear inconsistent. However, the temporal pattern of these signals is consistent. Therefore, ongoing research on motor learning is investigating how these timed signals develop and their role in motor learning.

Steroidogenesis

The inferior olivary nucleus (ION) expresses key enzymes involved in steroidogenesis required for

neuroprotection Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal l ...

and maintenance.Sierra A1, Azcoitia I, Garcia-Segura L. ''Endogenous estrogen formation is neuroprotective in model of cerebellar ataxia.'' Endocrine. 2003 Jun;21(1):43-51. The most crucial of these enzymes is

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze man ...

, which is the enzyme that is necessary for the conversion of

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

into

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

. Without aromatase, the ION is unable to make estradiol, and cannot recover from injury properly.

Clinical significance

Because the inferior olivary nucleus (ION) is tightly associated with the cerebellum, lesions in either the IO or the cerebellum results in degeneration in the other. There is little known about damage to the inferior olivary nucleus (IO) independent from the cerebellum. To date, the only known disorder which specifically targets the ION is an extremely rare form of degeneration called hypertrophic olivary degeneration (HOD). Although the ION is not often investigated on its own, degeneration in the ION has been identified in disorders that are typically associated with the cerebellum. These disorders include supranuclear palsy, Leigh disease, and SCA6, and there are several more. These disorders all involve motor coordination. Dysfunction of the ION is also believed to play a central role in the etiology of essential tremor, though that convention is not universally accepted.

Additional images

File:Gray707.png, Sagittal section through right cerebellar hemisphere. The right olive has also been cut sagittally.

References

External links

* {{DEFAULTSORT:Inferior Olivary Nucleus Medulla oblongata