Subthalamic nucleus

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Subthalamic nucleus

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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).

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The?subthalamic nucleus?is a small lens-shaped?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?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,[1]?and the term?corpus Luysi?or?Luys' body?is still sometimes used.

Contents

·?1Anatomy

·?1.1Structure

·?1.2Afferent axons

·?1.3Efferent targets

·?2Physiology

·?2.1Subthalamic nucleus

·?2.2Lateropallido-subthalamic system

·?3Pathophysiology

·?4Function

·?5Additional images

·?6See also

·?7References

Anatomy[edit]

Structural connectivity of the human subthalamic nucleus as visualized through?diffusion-weighted MRI.

Structure[edit]

The principal type of?neuron?found in the subthalamic nucleus has rather long, sparsely spiny?dendrites.[2][3]?In the more centrally located neurons, the dendritic arbors have a more?ellipsoidal?shape.[4]?The dimensions of these arbors (1200?μm, 600?μm, and 300?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?GABAergic?interneurons?that participate in the local circuitry; however, the dendritic arbors of subthalamic neurons shy away from the border and primarily interact with one another.[5]

Afferent axons[edit]

The subthalamic nucleus receives its main input from the?external globus pallidus?(GPe),[6]?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). These?afferents?are GABAergic, inhibiting neurons in the subthalamic nucleus. Excitatory, glutamatergic inputs come from the?cerebral cortex?(particularly the motor cortex)

(這句話非常重要。我研究分析判斷的結(jié)果是motor cortex中的BA4 cortex投射到subthalamic nucleus，而BA6 cortex不投射到subthalamic nucleus。)

(皮層到subthalamic nucleus的這個投射，很有可能是對動作結(jié)束的精準控制，畢竟subthalamic nucleus興奮reticulata和internal globus pallidus的效果是去抑制丘腦的VA、VL以及讓眼球不動。當然，subthalamic nucleus出現(xiàn)大面積地興奮導(dǎo)致了悲傷的情緒感受，這樣的悲傷情緒狀態(tài)是可以自己消亡的，因為reticulata抑制了pars compacta，從而減少了dorsal striatum對external globus pallidus的抑制性輸出，這樣external globus pallidus會自動放電去抑制subthalamic nucleus；接受疼痛信息的central median nucleus in the intralaminar 同時投射到putamen和subthalamic nucleus，讓internal globus pallidus同時接收抑制型遞質(zhì)和興奮型遞質(zhì)，正負離子同時大量進入細胞，大概這對neuron來說是個不健康的狀態(tài)吧，這或許是疼痛所帶來的不可忍受的原因吧，然后主觀意識也可以自我選擇是讓internal globus pallidus興奮或者抑制，痛的時候似乎眼球也不能轉(zhuǎn)動。好在可以通過magnus raphe nucleus來抑制疼痛信息的傳導(dǎo)。除此還有個疼痛是常見的現(xiàn)象，就是全身肌肉的強直，即通過強化external globus pallidus的放電來抑制subthalamic nucleus，避免internal globus pallidus同時接收抑制型遞質(zhì)和興奮型遞質(zhì)，但是此時external globus pallidus也會強烈輸出抑制到thalamic reticular formation，從而使后者放松對丘腦的抑制。要是遇到疼痛時選擇去抑制putamen，來避免internal globus pallidus同時接收抑制型遞質(zhì)和興奮型遞質(zhì)，也應(yīng)該是一種常見處理方案。)

, and from the pars?parafascicularis?of the?central complex

（或許，這是被動受擊時產(chǎn)生的強直。換句話說，疼痛信息可以通過STN來減少個體的主動行為，不影響被動行為，但是可以通過reticulata來影響眼動。如果疼痛信息能夠到達putamen，那么就可以影響主動行為，事實上一部分疼痛信息是可以到達中腦的多巴胺系統(tǒng)核團，從而影響主動行為，但是還有一部分來自內(nèi)臟的疼痛信息顯然是可以強烈抑制主動行為。在我看來，STN的功能是非常明確的。）

. The subthalamic nucleus also receives?neuromodulatory?inputs, notably?dopaminergic?axons from the?substantia nigra?pars compacta.

（這就有意思了，subthalamic nucleus投射到reticulata從而抑制compacta，然后compacta還投射到subthalamic nucleus，來興奮之，是為了避免compacta持續(xù)興奮嗎，從而達到compacta周期性興奮的效果？）

[7]?It also receives inputs from the?pedunculopontine nucleus

(但是，據(jù)其他wiki詞條，pedunculopontine nucleus也投射興奮axon到STN。).

Efferent targets[edit]

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（比如reticulata、internal globus pallidus，）.[8]?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.[8][9]?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).（在這前面的話是不是沒有沒有用？）

Some researchers have reported internal?axon?collaterals.[10]?However, there is little functional evidence for this.

Physiology[edit]

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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.?Green arrows?refer to excitatory?glutamatergic?pathways,?red arrowsrefer to inhibitory?GABAergic?pathways and?turquoise arrows?refer to?dopaminergic?pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.

Subthalamic nucleus[edit]

The first intracellular electrical recordings of subthalamic neurons were performed using sharp electrodes in a rat slice preparation.[citation needed]?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",[11]?since they can generate spontaneous?action potentials?at rates of 80 to 90?Hz in primates

（這個或許是人類、大猩猩、黑猩猩、紅毛猩猩在通常情況下活動頻率慢的原因吧，STN能夠在頂葉視覺信息的作用下去抑制主動行為，從而保證個體有較多的時間去觀察和思考。）.

Oscillatory and synchronous activity[12][13]?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[edit]

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"[14]?with synchronous bursts.

（最初的語言應(yīng)該是先建立聲音與頂葉視覺信息的聯(lián)系，完成發(fā)生與視覺信息的記憶（注意，對英語而言，是建立元音與頂葉視覺信息的聯(lián)系），然后在此基礎(chǔ)上才能做到連續(xù)不斷地發(fā)聲，建立顳葉的視覺信息與連續(xù)聲音之間的聯(lián)系（注意，這里指的是多音節(jié)與顳葉視覺信息的聯(lián)系），前者處于NE狀態(tài)，后者處于DA狀態(tài)；然后對于多音節(jié)發(fā)音的結(jié)束用頂葉的視覺信息來興奮STN從而截止發(fā)音，這建立了多音節(jié)聲音與頂葉視覺信息的記憶聯(lián)系，在這個多音節(jié)的過程中，用到了顳葉信息，并且還把頂葉視覺信息給拉進來，實現(xiàn)了顳葉視覺信息-聲音-頂葉視覺信息三者的共同活動。差不多，這應(yīng)該就是口語（不包含認字）的工作機制吧，這個可以從2、3歲孩子掌握語言的過程中觀察到。）

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?mm3, the subthalamic nucleus only 158?mm3.[15]?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.[16]?The activity of the medial pallidum is influenced by afferences from the lateral pallidum and from the subthalamic nucleus.[17]?The same for the?substantia nigra pars reticulata.[9]?The subthalamic nucleus sends axons to another regulator: the pedunculo-pontine complex?（應(yīng)該是pedunculopontine nucleus。）(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.[18]

Pathophysiology[edit]

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 modify the activity of subthalamic neurons. However, it has been shown in thalamic slices from mice,[19]?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.

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.

As one of the STN's suspected functions is in impulse control

(突然停止行為（比如投擲行為）中停止的那部分控制，而一側(cè)STN的損傷導(dǎo)致停止部分控制喪失，導(dǎo)致投擲行為得不到突然停止（比如緊握球的手沒有及時松手），類似的，從而增加了動作發(fā)生的時間。)

, dysfunction in this region has been implicated in?obsessive–compulsive disorder.[20]?Artificially stimulating the STN has shown some promise in correcting severe impulsive behavior

（難道STN損傷的人更容易沖動？）

?and may later be used as an alternative treatment for the disorder.[21]

Function[edit]

The function of the STN is unknown, but current theories place it as a component of the?basal ganglia?control system that may perform action selection. It is thought to implement the so-called "hyperdirect pathway" of motor control, contrasting with the direct and indirect pathways implemented elsewhere in the basal ganglia. STN dysfunction has also been shown to increase impulsivity in individuals presented with two equally rewarding stimuli.[22]

Research has suggested that the subthalamus is an?extrapyramidal?center. It holds muscular responses in check, and damage may result in hemiballism (a violent flinging of the arm and leg on one side of the body).[23]