View source for Subthalamic nucleus

{{short description|Small lens-shaped nucleus in the brain}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox brain
| Name            = Subthalamic nucleus
| Latin           = nucleus subthalamicus
| Image           = Basal-ganglia-coronal-sections-large.png
| Caption         = Coronal slices of human brain showing the [[basal ganglia]] ([[external globus pallidus]] (GPe) and [[internal globus pallidus]] (GPi)), '''subthalamic nucleus''' (STN) and [[substantia nigra]] (SN).
| Image2          = DA-loops in PD.svg
| Caption2        = DA-loops in [[Parkinson's disease]]
| Acronym         = STN
| IsPartOf        = [[Subthalamus]] (physically); [[basal ganglia]] (functionally)
| Components      =
| Artery          =
| Vein            =
}}
The '''subthalamic nucleus''' ('''STN''') is a small lens-shaped [[Nucleus (neuroanatomy)|nucleus]] in the [[brain]] where it is, from a functional point of view, part of the [[basal ganglia]] system. In terms of anatomy, it is the major part of the [[subthalamus]]. As suggested by its name, the subthalamic nucleus is located [[Anatomical terms of location|ventral]] to the [[thalamus]]. It is also dorsal to the [[substantia nigra]] and medial to the [[internal capsule]]. 

==Anatomy==
[[File:Ultra-High-Field-MRI-Post-Mortem-Structural-Connectivity-of-the-Human-Subthalamic-Nucleus-Video1.ogv|thumb|Structural connectivity of the human subthalamic nucleus as visualized through [[diffusion-weighted MRI]].]]

=== Structure ===
The principal type of [[neuron]] found in the subthalamic nucleus has rather long, sparsely spiny [[dendrite]]s.<ref name=Afsharpour1985>{{cite journal | vauthors = Afsharpour S | title = Light microscopic analysis of Golgi-impregnated rat subthalamic neurons | journal = The Journal of Comparative Neurology | volume = 236 | issue = 1 | pages = 1–13 | date = June 1985 | pmid = 4056088 | doi = 10.1002/cne.902360102 | s2cid = 12482772 }}</ref><ref>{{cite journal | vauthors = Rafols JA, Fox CA | title = The neurons in the primate subthalamic nucleus: a Golgi and electron microscopic study | journal = The Journal of Comparative Neurology | volume = 168 | issue = 1 | pages = 75–111 | date = July 1976 | pmid = 819471 | doi = 10.1002/cne.901680105 | s2cid = 11962279 }}</ref> In the more centrally located neurons, the dendritic arbors have a more [[ellipsoid]]al shape.<ref>{{cite journal | vauthors = Yelnik J, Percheron G | title = Subthalamic neurons in primates: a quantitative and comparative analysis | journal = Neuroscience | volume = 4 | issue = 11 | pages = 1717–1743 | year = 1979 | pmid = 117397 | doi = 10.1016/0306-4522(79)90030-7 | s2cid = 40909863 }}</ref> The dimensions of these arbors (1200&nbsp;μm, 600&nbsp;μm, and 300&nbsp;μm) are similar across many species—including rat, cat, monkey and human—which is unusual. However, the number of neurons increases with brain size as well as the external dimensions of the nucleus. The principal neurons are [[glutamatergic]], which give them a particular functional position in the basal ganglia system. In humans there are also a small number (about 7.5%) of [[GABA]]ergic [[interneuron]]s that participate in the local circuitry; however, the dendritic arbors of subthalamic neurons shy away from the border and primarily interact with one another.<ref>{{cite journal | vauthors = Lévesque JC, Parent A | title = GABAergic interneurons in human subthalamic nucleus | journal = Movement Disorders | volume = 20 | issue = 5 | pages = 574–584 | date = May 2005 | pmid = 15645534 | doi = 10.1002/mds.20374 | s2cid = 9551517 }}</ref>

The structure of the subthalamic nucleus has not yet been fully explored and understood, but it is likely composed of several internal domains. The primate subthalamic nucleus is often divided in three internal anatomical-functional domains. However, this so-called ''tripartite model'' has been debated because it does not fully explain the complexity of the subthalamic nucleus in brain function.<ref>{{cite journal | vauthors = Alkemade A, Forstmann BU | title = Do we need to revise the tripartite subdivision hypothesis of the human subthalamic nucleus (STN)? | journal = NeuroImage | volume = 95 | pages = 326–329 | date = July 2014 | pmid = 24642281 | doi = 10.1016/j.neuroimage.2014.03.010 | s2cid = 11010595 }}</ref><ref>{{cite journal | vauthors = Lambert C, Zrinzo L, Nagy Z, Lutti A, Hariz M, Foltynie T, Draganski B, Ashburner J, Frackowiak R | title = Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion weighted imaging | journal = NeuroImage | volume = 60 | issue = 1 | pages = 83–94 | date = March 2012 | pmid = 22173294 | pmc = 3315017 | doi = 10.1016/j.neuroimage.2011.11.082 }}</ref>

===Afferent axons===
The subthalamic nucleus receives its main input from the [[external globus pallidus]] (GPe),<ref name="pmid2350684">{{cite journal | vauthors = Canteras NS, Shammah-Lagnado SJ, Silva BA, Ricardo JA | title = Afferent connections of the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxidase study in the rat | journal = Brain Research | volume = 513 | issue = 1 | pages = 43–59 | date = April 1990 | pmid = 2350684 | doi = 10.1016/0006-8993(90)91087-W | s2cid = 22996045 }}</ref> not so much through the [[ansa lenticularis]] as often said but by radiating 'comb' fibers crossing the medial pallidum first and the internal capsule (forming part of [[Ludwig Edinger|Edinger]]'s comb system, see figure), as well as the ansa subthalamica.<ref>{{cite journal | vauthors = Alho EJ, Alho AT, Horn A, Martin MD, Edlow BL, Fischl B, Nagy J, Fonoff ET, Hamani C, Heinsen H | title = The Ansa Subthalamica: A Neglected Fiber Tract | journal = Movement Disorders | volume = 35 | issue = 1 | pages = 75–80 | date = January 2020 | pmid = 31758733 | doi = 10.1002/mds.27901 }}</ref> These [[afferent nerve fiber|afferents]] are GABAergic, inhibiting neurons in the subthalamic nucleus. Excitatory, glutamatergic inputs come from the [[cerebral cortex]] (entire frontal cortex with a predominance for motor, premotor and oculomotor input to the posterolateral part of the nucleus), and from the pars [[parafascicularis]] of the [[central complex]]. The subthalamic nucleus also receives [[neuromodulator]]y inputs, notably [[dopaminergic]] axons from the [[substantia nigra]] pars compacta.<ref>{{cite journal | vauthors = Cragg SJ, Baufreton J, Xue Y, Bolam JP, Bevan MD | title = Synaptic release of dopamine in the subthalamic nucleus | journal = The European Journal of Neuroscience | volume = 20 | issue = 7 | pages = 1788–1802 | date = October 2004 | pmid = 15380000 | doi = 10.1111/j.1460-9568.2004.03629.x | s2cid = 14698708 | doi-access = free }}</ref>
It also receives inputs from the [[pedunculopontine nucleus]].

===Efferent targets===
The axons of subthalamic nucleus neurons leave the nucleus dorsally. The efferent axons are glutamatergic (excitatory). Except for the connection to the striatum (17.3% in macaques), most of the subthalamic principal neurons are multitargets and directed to the other elements of the core of the basal ganglia.<ref name="pmid418083">{{cite journal | vauthors = Nauta HJ, Cole M | title = Efferent projections of the subthalamic nucleus: an autoradiographic study in monkey and cat | journal = The Journal of Comparative Neurology | volume = 180 | issue = 1 | pages = 1–16 | date = July 1978 | pmid = 418083 | doi = 10.1002/cne.901800102 | s2cid = 43046462 }}</ref> Some send axons to the substantia nigra medially and to the medial and lateral nuclei of the pallidum laterally (3-target, 21.3%). Some are 2-target with the lateral pallidum and the substantia nigra (2.7%) or the lateral pallidum and the medial (48%). Less are single target for the lateral pallidum. In the pallidum, subthalamic terminals end in bands parallel to the pallidal border.<ref name="pmid418083"/><ref name=Smith1990>{{cite journal | vauthors = Smith Y, Hazrati LN, Parent A | title = Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method | journal = The Journal of Comparative Neurology | volume = 294 | issue = 2 | pages = 306–323 | date = April 1990 | pmid = 2332533 | doi = 10.1002/cne.902940213 | s2cid = 9667393 }}</ref> When all axons reaching this target are added, the main efference of the subthalamic nucleus is, in 82.7% of the cases, clearly the [[internal globus pallidus]] (GPi).

Some researchers have reported internal [[axon]] collaterals.<ref>{{cite journal | vauthors = Kita H, Chang HT, Kitai ST | title = The morphology of intracellularly labeled rat subthalamic neurons: a light microscopic analysis | journal = The Journal of Comparative Neurology | volume = 215 | issue = 3 | pages = 245–257 | date = April 1983 | pmid = 6304154 | doi = 10.1002/cne.902150302 | s2cid = 32152785 }}</ref> However, there is little functional evidence for this.

==Physiology==
[[File:Basal ganglia circuits.svg|thumb|320px|Anatomical overview of the main circuits of the [[basal ganglia]]. Subthalamic nucleus is shown in red. Picture shows 2 coronal slices that have been superimposed to include the involved basal ganglia structures. + and - signs at the point of the arrows indicate respectively whether the pathway is excitatory or inhibitory in effect. {{color|green|Green arrows}} refer to excitatory [[:en:Glutamic acid|glutamatergic]] pathways, {{color|red|red arrows}} refer to inhibitory [[:en:gamma-Aminobutyric acid|GABAergic]] pathways and {{color|turquoise|turquoise arrows}} refer to [[:en:dopamine|dopaminergic]] pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.]]

===Subthalamic nucleus===
The first intracellular electrical recordings of subthalamic neurons were performed using sharp electrodes in a rat slice preparation.{{Citation needed|date=May 2010}}  In these recordings three key observations were made, all three of which have dominated subsequent reports of subthalamic firing properties. The first observation was that, in the absence of current injection or synaptic stimulation, the majority of cells were spontaneously firing. The second observation is that these cells are capable of transiently firing at very high frequencies.   The third observation concerns non-linear behaviors when cells are transiently depolarized after being hyperpolarized below –65mV. They are then able to engage voltage-gated calcium and sodium currents to fire bursts of action potentials.

Several recent studies have focused on the autonomous pacemaking ability of subthalamic neurons. These cells are often referred to as "fast-spiking pacemakers",<ref>{{cite journal | vauthors = Surmeier DJ, Mercer JN, Chan CS | title = Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway? | journal = Current Opinion in Neurobiology | volume = 15 | issue = 3 | pages = 312–318 | date = June 2005 | pmid = 15916893 | doi = 10.1016/j.conb.2005.05.007 | s2cid = 42900941 | author-link1 = D. James Surmeier }}</ref> since they can generate spontaneous [[action potential]]s at rates of 80 to 90&nbsp;Hz in primates.

Oscillatory and synchronous activity<ref>{{cite journal | vauthors = Levy R, Hutchison WD, Lozano AM, Dostrovsky JO | title = High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor | journal = The Journal of Neuroscience | volume = 20 | issue = 20 | pages = 7766–7775 | date = October 2000 | pmid = 11027240 | pmc = 6772896 | doi = 10.1523/JNEUROSCI.20-20-07766.2000 }}</ref><ref>{{cite journal | vauthors = Lintas A, Silkis IG, Albéri L, Villa AE | title = Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus | journal = Brain Research | volume = 1434 | issue = 3 | pages = 142–151 | date = January 2012 | pmid = 21959175 | doi = 10.1016/j.brainres.2011.09.005 | s2cid = 14636489 | url = https://inserm.hal.science/inserm-00851266/file/Lintas_2012_Dopamine_Deficiency_AA.pdf }}</ref> is likely to be a typical pattern of discharge in subthalamic neurons recorded from patients and animal models characterized by the loss of dopaminergic cells in the [[substantia nigra pars compacta]], which is the principal pathology that underlies [[Parkinson's disease]].

=== Lateropallido-subthalamic system===
Strong reciprocal connections link the subthalamic nucleus and the external segment of the [[globus pallidus]]. Both are fast-spiking pacemakers. Together, they are thought to constitute the "central pacemaker of the basal ganglia"<ref>{{cite journal | vauthors = Plenz D, Kital ST | title = A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus | journal = Nature | volume = 400 | issue = 6745 | pages = 677–682 | date = August 1999 | pmid = 10458164 | doi = 10.1038/23281 | s2cid = 4356230 | bibcode = 1999Natur.400..677P }}</ref> with synchronous bursts.

The connection of the lateral pallidum with the subthalamic nucleus is also the one in the [[basal ganglia]] system where the reduction between emitter/receiving elements is likely the strongest. In terms of volume, in humans, the lateral pallidum measures 808&nbsp;mm<sup>3</sup>, the subthalamic nucleus only 158&nbsp;mm<sup>3</sup>.<ref>{{cite journal | vauthors = Yelnik J | title = Functional anatomy of the basal ganglia | journal = Movement Disorders | volume = 17 | issue = Suppl. 3 | pages = S15–S21 | year = 2002 | pmid = 11948751 | doi = 10.1002/mds.10138 | s2cid = 40925638 }}</ref> This translated in numbers of neurons represents a strong compression with loss of map precision.

Some axons from the lateral pallidum go to the striatum.<ref>{{cite journal | vauthors = Sato F, Lavallée P, Lévesque M, Parent A | title = Single-axon tracing study of neurons of the external segment of the globus pallidus in primate | journal = The Journal of Comparative Neurology | volume = 417 | issue = 1 | pages = 17–31 | date = January 2000 | pmid = 10660885 | doi = 10.1002/(SICI)1096-9861(20000131)417:1<17::AID-CNE2>3.0.CO;2-I | s2cid = 84665164 }}</ref> The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus.<ref>{{cite journal | vauthors = Smith Y, Wichmann T, DeLong MR | title = Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys | journal = The Journal of Comparative Neurology | volume = 343 | issue = 2 | pages = 297–318 | date = May 1994 | pmid = 8027445 | doi = 10.1002/cne.903430209 | s2cid = 24968074 }}</ref> The same for the [[substantia nigra pars reticulata]].<ref name=Smith1990 /> The subthalamic nucleus  sends axons to another regulator: the pedunculo-pontine complex (id).

The lateropallido-subthalamic system is thought to play a key role in the generation of the patterns of activity seen in [[Parkinson's disease]].<ref>{{cite journal | vauthors = Bevan MD, Magill PJ, Terman D, Bolam JP, Wilson CJ | title = Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network | journal = Trends in Neurosciences | volume = 25 | issue = 10 | pages = 525–531 | date = October 2002 | pmid = 12220881 | doi = 10.1016/S0166-2236(02)02235-X | s2cid = 8127062 }}</ref>

==Pathophysiology==
Lesioning the STN leads to alleviation of motor symptoms such as [[Hypokinesia|akinesia]], [[Rigidity (neurology)|rigidity]], and [[tremor]] in [[Parkinson's disease|Parkinson disease]]. This was first shown in the [[MPTP]] primate model in a paper by [[Hagai Bergman|Bergman]] and colleagues.<ref>{{cite journal | vauthors = Bergman H, Wichmann T, DeLong MR | title = Reversal of experimental parkinsonism by lesions of the subthalamic nucleus | journal = Science | volume = 249 | issue = 4975 | pages = 1436–1438 | date = September 1990 | pmid = 2402638 | doi = 10.1126/science.2402638 | bibcode = 1990Sci...249.1436B }}</ref> This inspired Benazzouz and colleagues to probe deep brain stimulation of the nucleus, which was known to exert similar effects as ablative lesions.<ref>{{cite journal | vauthors = Benazzouz A, Gross C, Féger J, Boraud T, Bioulac B | title = Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys | journal = The European Journal of Neuroscience | volume = 5 | issue = 4 | pages = 382–389 | date = April 1993 | pmid = 8261116 | doi = 10.1111/j.1460-9568.1993.tb00505.x }}</ref> Soon after, the team of [[Alim Louis Benabid]] showed that deep brain stimulation of the nucleus leads to symptom relief in human patients with Parkinson disease, as well,<ref>{{cite journal | vauthors = Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J | title = [Effects of the stimulation of the subthalamic nucleus in Parkinson disease] | journal = Revue Neurologique | volume = 149 | issue = 3 | pages = 175–176 | date = 1993 | pmid = 8235208 }}</ref> which led to the establishment of the currently [[Food and Drug Administration|FDA]] approved and widely applied form of [[deep brain stimulation]]. The first to be stimulated are the terminal arborisations of afferent axons, which modify the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice,<ref>{{cite journal | vauthors = Bekar L, Libionka W, Tian GF, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos R, Nedergaard M | title = Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor | journal = Nature Medicine | volume = 14 | issue = 1 | pages = 75–80 | date = January 2008 | pmid = 18157140 | doi = 10.1038/nm1693 | s2cid = 7107064 }}</ref> that the stimulus also causes nearby astrocytes to release [[adenosine triphosphate]] (ATP), a precursor to [[adenosine]] (through a catabolic process). In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus mimicking [[ablation]] of the subthalamic nucleus.

Before the [[Hagai Bergman|Bergman]] paper, the stereotactic field avoided lesioning the nucleus, since it was known that unilateral destruction or disruption of the subthalamic nucleus — which may result from naturally occurring strokes — may lead to [[hemiballismus]]. While this remains generally true, iatrogenic lesioning of the STN has been carried out numerous times and has recently gained new wind with the advent of [[HIFU|MR guided focused ultrasound]], which has also been probed for subthalamic nucleotomies to treat Parkinson disease.<ref>{{cite journal | vauthors = Martínez-Fernández R, Máñez-Miró JU, Rodríguez-Rojas R, Del Álamo M, Shah BB, Hernández-Fernández F, Pineda-Pardo JA, Monje MH, Fernández-Rodríguez B, Sperling SA, Mata-Marín D, Guida P, Alonso-Frech F, Obeso I, Gasca-Salas C, Vela-Desojo L, Elias WJ, Obeso JA | title = Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease | journal = The New England Journal of Medicine | volume = 383 | issue = 26 | pages = 2501–2513 | date = December 2020 | pmid = 33369354 | doi = 10.1056/NEJMoa2016311 }}</ref> Curiously, a team around [[Michael D. Fox|Michael Fox]] could recently show that, while some lesions that led to hemiballism were indeed in and around the STN, the majority of reported cases were in other regions of the brain.<ref>{{cite journal | vauthors = Laganiere S, Boes AD, Fox MD | title = Network localization of hemichorea-hemiballismus | journal = Neurology | volume = 86 | issue = 23 | pages = 2187–2195 | date = June 2016 | pmid = 27170566 | pmc = 4898318 | doi = 10.1212/WNL.0000000000002741 }}</ref>

As one of the STN's suspected functions is in impulse control, dysfunction in this region has been implicated in [[obsessive–compulsive disorder]].<ref>{{cite book| vauthors = Carter R |title=The Human Brain Book|pages=58,233}}</ref> Application of high frequency pulses by [[deep brain stimulation]] has shown some promise in correcting severe impulsive behavior and has been [[Food and Drug Administration|FDA]] approved for treatment resistant cases with the disorder.<ref>{{cite journal | vauthors = Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, du Montcel ST, Yelnik J, Chéreau I, Arbus C, Raoul S, Aouizerate B, Damier P, Chabardès S, Czernecki V, Ardouin C, Krebs MO, Bardinet E, Chaynes P, Burbaud P, Cornu P, Derost P, Bougerol T, Bataille B, Mattei V, Dormont D, Devaux B, Vérin M, Houeto JL, Pollak P, Benabid AL, Agid Y, Krack P, Millet B, Pelissolo A | title = Subthalamic nucleus stimulation in severe obsessive-compulsive disorder | journal = The New England Journal of Medicine | volume = 359 | issue = 20 | pages = 2121–2134 | date = November 2008 | pmid = 19005196 | doi = 10.1056/NEJMoa0708514 | doi-access = free }}</ref>

== Function ==
The function of the STN is not fully understood but it is believed that, as a component of the basal ganglia, it plays a part in the so-called "hyperdirect" and "indirect" pathways of motor control, as opposed to the direct pathway which bypasses the STN on its way from the Striatum to the internal pallidum. STN dysfunction has been implicated in motor symptoms such as rigidity, bradykinesia and tremor,<ref>{{cite journal | vauthors = Bergman H, Wichmann T, DeLong MR | title = Reversal of experimental parkinsonism by lesions of the subthalamic nucleus | journal = Science | volume = 249 | issue = 4975 | pages = 1436–1438 | date = September 1990 | pmid = 2402638 | doi = 10.1126/science.2402638 | bibcode = 1990Sci...249.1436B }}</ref> behavioral features such as stopping of ongoing movements<ref>{{cite journal | vauthors = Lofredi R, Auernig GC, Irmen F, Nieweler J, Neumann WJ, Horn A, Schneider GH, Kühn AA | title = Subthalamic stimulation impairs stopping of ongoing movements | journal = Brain | volume = 144 | issue = 1 | pages = 44–52 | date = February 2021 | pmid = 33253351 | doi = 10.1093/brain/awaa341 }}</ref> or impulsivity in individuals presented with two equally rewarding stimuli.<ref>{{cite journal | vauthors = Frank MJ, Samanta J, Moustafa AA, Sherman SJ | title = Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism | journal = Science | volume = 318 | issue = 5854 | pages = 1309–1312 | date = November 2007 | pmid = 17962524 | doi = 10.1126/science.1146157 | s2cid = 2718110 | doi-access = free | bibcode = 2007Sci...318.1309F }}</ref>

The physiological role of the STN has been for long hidden by its pathological role. But lately, the research on the physiology of the STN led to the discovery that the STN is required to achieve intended movement, including locomotion, balance and motor coordination. It is  involved in stopping or interrupting on-going motor tasks. Moreover, STN excitation was generally correlated with significant reduction in locomotor activity, while in contrast, STN inhibition enhanced locomotion.<ref>{{cite journal | vauthors = Aron AR, Behrens TE, Smith S, Frank MJ, Poldrack RA | title = Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI | journal = The Journal of Neuroscience | volume = 27 | issue = 14 | pages = 3743–3752 | date = April 2007 | pmid = 17409238 | pmc = 6672420 | doi = 10.1523/JNEUROSCI.0519-07.2007 }}</ref><ref>{{cite journal | vauthors = Fife KH, Gutierrez-Reed NA, Zell V, Bailly J, Lewis CM, Aron AR, Hnasko TS | title = Causal role for the subthalamic nucleus in interrupting behavior | journal = eLife | volume = 6 | article-number = e27689 | date = July 2017 | pmid = 28742497 | pmc = 5526663 | doi = 10.7554/eLife.27689 | veditors = Uchida N | doi-access = free }}</ref><ref>{{cite journal | vauthors = Guillaumin A, Serra GP, Georges F, Wallén-Mackenzie Å | title = Experimental investigation into the role of the subthalamic nucleus (STN) in motor control using optogenetics in mice | journal = Brain Research | volume = 1755 | article-number = 147226 | date = March 2021 | pmid = 33358727 | doi = 10.1016/j.brainres.2020.147226 | doi-access = free }}</ref>

==History==
The STN was first described by [[Jules Bernard Luys]] in 1865.<ref>{{cite book | vauthors = Luys JB | author-link=Jules Bernard Luys | year=1865 | title=Recherches sur le système cérébro-spinal, sa structure, ses fonctions et ses maladies | publisher=Baillière | location=Paris | language=fr}}</ref> 

==Additional images==
<gallery>
 File:Gray717.png|Coronal section of brain immediately in front of pons. Subthalamic nucleus labeled as "Nucleus of Luys".
</gallery>

== See also ==
{{Commons category|Subthalamic nucleus}}
* [[Primate basal ganglia]]
* [[Mesencephalic locomotor region]]

== References ==
{{Reflist}}

{{Diencephalon}}
{{Neural tracts}}
{{Authority control}}

{{DEFAULTSORT:Subthalamic Nucleus}}
[[Category:Subthalamus]]
[[Category:Basal ganglia]]