Inferior olivary nucleus

Template:Short description Template:Infobox brain The inferior olivary nucleus (ION) is a structure found in the medulla oblongata underneath the superior olivary nucleus.<ref name=":0">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. Template:ISBN.</ref> In vertebrates, the ION is known to coordinate signals from the spinal cord to the cerebellum to regulate motor coordination and learning.<ref name=":3">Schweighofer N, Lang EJ, Kawato M. Role of the olivo-cerebellar complex in motor learning and control. Frontiers in Neural Circuits. 2013;7:94. {{#invoke:doi|main}}.</ref> These connections have been shown to be tightly associated, as degeneration of either the cerebellum or the ION results in degeneration of the other.<ref>Template:Cite book</ref><ref>Gatlin JL, Wineman R, Schlakman B, Buciuc R, Khan M. Hypertrophic Olivary Degeneration After Resection of a Pontine Cavernous Malformation: A Case Report. Journal of Radiology Case Reports. 2011;5(3):24-29. {{#invoke:doi|main}}.</ref>

Neurons of the ION are glutamatergic and receive inhibitory input via GABA receptors.<ref name=":0" /> 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.<ref name=":1">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. {{#invoke:doi|main}}</ref> 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.<ref name=":1" />

StructureEdit

The inferior olivary nucleus (ION) has a distinct laminar structure.<ref name=":0" /> 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.<ref name=":0" /> Their axons are referred to as climbing fibers. These climbing fibers leave the ION medially through the hilum, cross the midline, and ascend into the cerebellum via the inferior cerebellar peduncle.<ref name=":0" /> The target for each climbing fiber is a specific neuron in the cerebellum referred to as a Purkinje Cell. 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.<ref name=":2">Template:Cite journal</ref>

Primary olivary nucleus (PO) – This is the major laminar structure, and its distinct folds can be seen clearly.<ref name=":2" />
- The PO receives signals from other components of the brainstem, such as the red nucleus and the N. Darkschewitsch. The PO also receives signals from the cerebral cortex.<ref name=":2" />
- The PO targets the intermediate cerebellum as well as the cerebellar hemispheres.<ref name=":2" />
Medial accessory olivary nucleus (MAO) – This nucleus is between the PO and the pyramids. It is visualized as a curved lamina.<ref name=":2" />
- The MAO receives signals from the tectum and the pretectum.<ref name=":2" />
- Climbing fibers from the MAO synapse with the vermis, the flocculus, and the cerebellar hemispheres<ref name=":2" />
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.<ref name=":2" />
- The DAO receives signals from the spinal cord and the dorsal column nuclei.<ref name=":2" />
- The DAO synapses with vermis.<ref name=":2" />

FunctionEdit

Motor coordination and learningEdit

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.<ref>Martin TA, Keating JG, Goodkin HP, Bastian AJ, Thach WT. Throwing while looking through prisms. I. Focal olivocerebellar lesions impair adaptation. Brain 1996; 119: 1183-1198.</ref> Further investigation of the neuroanatomy confirmed the intimate connection between the IO and the cerebellum in motor coordination and learning.<ref name=":3" />

The IO sends signals to the cerebellum based on information sent from the spino-olivary tract. Regulation following this point is highly debated. The original hypothesis as to how the IO influenced the cerebellum involved long term depression (LTD).<ref name=":3" /> 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.<ref name=":4">Liu T, Xu D, Ashe J, Bushara K. Specificity of inferior olive response to stimulus timing. J Neurophysiol 2008; 100: 1557-61.</ref> 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.<ref name=":4" /> Therefore, ongoing research on motor learning is investigating how these timed signals develop and their role in motor learning.

SteroidogenesisEdit

The inferior olivary nucleus (ION) expresses key enzymes involved in steroidogenesis required for neuroprotection and maintenance.<ref name=":5">Sierra A1, Azcoitia I, Garcia-Segura L. Endogenous estrogen formation is neuroprotective in model of cerebellar ataxia. Endocrine. 2003 Jun;21(1):43-51.</ref> The most crucial of these enzymes is aromatase, which is the enzyme that is necessary for the conversion of testosterone into estradiol.<ref>Biegon A. In vivo visualization of aromatase in animals and humans. Frontiers in Neuroendocrinology. 2016;40:42-51. {{#invoke:doi|main}}.</ref> Without aromatase, the ION is unable to make estradiol, and cannot recover from injury properly.<ref name=":5" />

Clinical significanceEdit

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).<ref>Template:Cite journal</ref>

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,<ref name=":6">Template:Cite journal</ref> Leigh disease,<ref name=":7">Template:Cite journal</ref> and SCA6,<ref name=":8">Template:Cite journal</ref> and there are several more. These disorders all involve motor coordination.<ref name=":6" /><ref name=":7" /><ref name=":8" /> 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.