Subthalamic nucleus
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{{Infobox Brain|
Name = Subthalamic nucleus |
Latin = nucleus subthalamicus |
GraySubject = |
GrayPage = |
Image = Basal-ganglia-coronal-sections-large.png |
Caption = Coronal slices of human brain showing the [[basal ganglia]], subthalamic nucleus (STN) and [[substantia nigra]] (SN). |
Image2 = DA-loops in PD.jpg |
Caption2 = DA-loops in [[Parkinson's disease]] |
IsPartOf = [[Basal ganglia]]|
Components = |
Artery = |
Vein = |
BrainInfoType = hier |
BrainInfoNumber = 418 |
MeshName = Subthalamic+Nucleus |
MeshNumber = A08.186.211.730.385.800.800 |
DorlandsPre = n_11 |
DorlandsSuf = 14166739 |
}}
The '''subthalamic nucleus''' is a small lens-shaped [[Nucleus (neuroanatomy)|nucleus]] in the [[brain]] where it is a part of the [[basal ganglia]] system. 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]]. It was first described by [[Jules Bernard Luys]] in 1865,<ref>{{cite book | last=Luys | first=Jules Bernard | authorlink=Jules Bernard Luys | year=1865 | title=Recherches sur le système cérébro-spinal, sa structure, ses fonctions et ses maladies | publisher=Baillière | location=Paris | language=French}}</ref> and the term ''corpus Luysi'' or ''Luys' body'' is still sometimes used.
==Anatomy==
===Structure===
The principal type of [[neuron]] found in the subthalamic nucleus has rather long [[dendrite]]s devoid of spines. The dendritic arborizations are ellipsoid, replicating in smaller dimension the shape of the nucleus.<ref>{{cite journal | author=Yelnik, J. & Percheron, G. | title=Subthalamic neurons in primates : a quantitative and comparative anatomy | journal=Neuroscience | year=1979 | pages=1717–1743 | volume=4 | issue=11 | pmid=117397 | doi=10.1016/0306-4522(79)90030-7}}</ref> The dimensions of these arborizations (1200,600 and 300 μm) are similar across many species—including rat, cat, monkey and man—which is unusual. However, the number of neurons increases across evolution as well as the external dimensions of the nucleus. Due to the bending of dendrites at the border, the subthalamic nucleus is a close nucleus, able to receive information only in its space. 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.<ref>{{cite journal | author=Levesque J.C. & Parent A. | title=GABAergic interneurons in human subthalamic nucleus | journal=Movement Disorders | year=2005 | pages=574–584 | volume=20 | issue=5 | pmid=15645534 | doi=10.1002/mds.20374}}</ref>
===Afferent axons===
The subthalamic nucleus receives its main input from the lateral pallidum ( external segment of the [[globus pallidus]]) (84.2% of its axons<ref name=Sato2000>{{cite journal | author=Sato F.; Parent M.; Levesque M.; & Parent A. | title=Axonal branching pattern of neurons of the subthalamic nucleus in primates | journal=Journal of Comparative Neurology | year=2000 | pages=142–152 | volume=424 | issue=1 | pmid=10888744 | doi=10.1002/1096-9861(20000814)424:1<142::AID-CNE10>3.0.CO;2-8}}</ref>), not so much through the ansa lenticularis as often said but by radiating fibers crossing the medial pallidum first and the internal capsule (see figure). This afference is GABAergic, inhibiting the neurons of the subthalamic nucleus. Excitatory, glutamatergic inputs come from the [[cerebral cortex]] (particularly the motor cortex), 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 | author=Cragg S.J.; Baufreton J.; Xue Y.; Bolam J.P.; & Bevan M.D. | title=Synaptic release of dopamine in the subthalamic nucleus | journal=European Journal of Neuroscience | year=2004 | pages=1788–1802 | volume=20 | issue=7 | pmid=15380000 | doi=10.1111/j.1460-9568.2004.03629.x}}</ref>
===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=Sato2000 /> 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>{{cite journal | author=Nauta, H.J.W. & Cole, M. | title=Efferent projections of the subthalamic nucleus : an autoradiographic study in monkey and cat | journal=Journal of Comparative Neurology | year=1978 | pages=1–16 | volume=180 | issue=1 | pmid=418083 | doi=10.1002/cne.901800102}}</ref><ref name=Smith1990>{{cite journal | author=Smith, Y.; Hazrati, L-N. & Parent, A. | title=Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method | journal=Journal of Comparative Neurology | year=1990 | pages=306–323 | volume=294 | issue=2 | pmid=2332533 | doi=10.1002/cne.902940213}}</ref> When all axons reaching this target are added, the main afference of the subthalamic nucleus is, in 82.7% of the cases, clearly the [[medial pallidum]] (internal segment of the globus pallidus).
Some researchers have reported internal [[axon]] collaterals.<ref>{{cite journal | author=Kita, H.; Chang, H.T.; & Kitai, S.T. | title=The morphology of intracellularly labeled rat subthalamic neurons: A light microscopic analysis | journal=Neuroscience | year=1983 | pages=245–257 | volume=215 | issue=3 | pmid=6304154}}</ref> However, there is little functional evidence for this.
==Physiology==
===Subthalamic nucleus===
The first intracellular electrical recordings of subthalamic neurons were performed using sharp electrodes in a rat slice preparation (Nakanishi et al., 1987). 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 | author=Surmeier D.J.; Mercer J.N.; & Chan C.S. | title=Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway? | journal=Current Opinion in Neurobiology | year=2005 | pages=312–318 | volume=15 | issue=3 | pmid=15916893 | doi=10.1016/j.conb.2005.05.007}}</ref> since they can generate spontaneous [[action potential]]s at rates of 80 to 90Hz in primates.
=== 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 | author=Plenz, D. & Kitai, S.T. | title=A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus | journal=Nature | year=1999 | pages=677–682 | volume=400 | issue=6745 | pmid=10458164 | doi=10.1038/23281}}</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 mesures 808 mm³, the subthalamic nucleus only 158 mm³.<ref>{{cite journal | author=Yelnik, J. | title=Functional anatomy of the basal ganglia | journal=Movement Disorders | year=2002 | pages=S15–S21 | volume=17 | issue=Suppl. 3 | pmid=11948751 | doi=10.1002/mds.10138}}</ref> This translated in numbers of neurons represents a strong compression with loss of map precision.
The systemic position of this circuit is particular in the basal ganglia system that may be revealed by contrast versus outputs subsystems. There are two output paths starting from the striatum. The first has a first relay in the medial pallidum (GABAegic inhibitory) and the second in the nigra reticulata (GABA). These two output subsystems do not send regulatory messages to other elements of the basal ganglia system: striatum, lateral pallidum or subthalamic nucleus. The lateropallido-subthalamic subsystem is particular in that it does the reverse. It does not send axons to the thalamus and from there to the cortex. All efferent axons of the subsystem are indeed returning inside the basal ganglia system. This topologically makes it a regulator. Some axons from the lateral pallidum go to the striatum.<ref>{{cite journal | author=Sato, F.; Lavallée, P.; Levesque, M. & Parent, A. | title=Single-axon tracing study of neurons of the external segment of the globus pallidus in primate | journal=Journal of Comparative Neurology | year=2000 | pages=17–31 | volume=417 | issue=1 | pmid=10660885 | doi=10.1002/(SICI)1096-9861(20000131)417:1<17::AID-CNE2>3.0.CO;2-I}}</ref> The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus.<ref>{{cite journal | author=Smith, Y.; Wichmann, T. & DeLong, M.R. | title=Synaptic innervation of neurones in the internal pallidal segment by the subthalamic nucleus and the external pallidum in monkeys | journal=Journal of Comparative Neurology | year=1994 | pages=297–318 | volume=343 | issue=2 | pmid=8027445 | doi=10.1002/cne.903430209}}</ref> The same for the nigra 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 | author=Bevan M.D.; Magill P.J.; Terman D.; Bolam J.P.; & Wilson CJ. | title=Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network | journal=Trends in Neurosciences | year=2002 | pages=525–531 | volume=25 | issue=10 | pmid=12220881 | doi=10.1016/S0166-2236(02)02235-X}}</ref>
==Physiopathology and interventions==
Chronic stimulation of the STN, called [[deep brain stimulation]] (DBS), is used to treat patients with [[Parkinson disease]]. The first to be stimulated are the terminal arborisations of afferent axons which modifies the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice<ref>{{cite journal | author=Bekar L., Libionka W., Tian G., 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 | year=2008 | pages=75–80 | volume=14 | issue=1 | doi=10.1038/nm1693 }}</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.
==Pathology==
Unilateral destruction or disruption of the subthalamic nucleus – which can commonly occur via a small vessel stroke in patients with diabetes, hypertension, or a history of smoking – produces [[hemiballismus]].
==Function==
The function of the STN is unknown, but current theories place it as a component of the [[basal ganglia]] control system which may perform action selection. STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli.<ref>{{cite journal | author=Frank, M.; Samanta, J.; Moustafa, A.; Sherman, S. | title=Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism | journal=Science | year=2007 | pages=1309–12 | volume=318 | issue=5854 | pmid=17962524 | doi=10.1126/science.1146157}}</ref>
==Additional images==
<gallery>
Image:Gray717.png|Coronal section of brain immediately in front of pons.
</gallery>
==References==
{{reflist|2}}
==See also==
* [[Primate basal ganglia]]
==External links==
* http://isc.temple.edu/neuroanatomy/lab/atlas/pdhn/
{{Basal ganglia}}
{{Diencephalon}}
[[Category:Cerebrum]]
[[it:Nucleo subtalamico]]
[[ja:視床下核]]
[[no:Nucleus subthalamicus]]